skip to content

Faculty of Biology

 

Scientists can detect brain tumours using a simple urine or blood plasma test

Fri, 23/07/2021 - 16:05

The team say that a test for detecting glioma using urine is the first of its kind in the world.

Although the research, published in EMBO Molecular Medicine, is in its early stages and only a small number of patients were analysed, the team say their results are promising.

The researchers suggest that in the future, these tests could be used by GPs to monitor patients at high risk of brain tumours, which may be more convenient than having an MRI every three months, which is the standard method.

When people have a brain tumour removed, the likelihood of it returning can be high, so they are monitored with an MRI scan every three months, which is followed by biopsy.

Blood tests for detecting different cancer types are a major focus of research for teams across the world, and there are some in use in the clinic. These tests are mainly based on finding mutated DNA, shed by tumour cells when they die, known as cell-free DNA (cfDNA).

However, detecting brain tumour cfDNA in the blood has historically been difficult because of the blood-brain-barrier, which separates blood from the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, preventing the passage of cells and other particles, such as cfDNA.

Researchers have previously looked at detecting cfDNA in CSF, but the spinal taps needed to obtain it can be dangerous for people with brain tumours so are not appropriate for patient monitoring.

Scientists have known that cfDNA with similar mutations to the original tumour can be found in blood and other bodily fluids such as urine in very low levels, but the challenge has been developing a test sensitive enough to detect these specific mutations.

The researchers, led by Dr Florent Mouliere who is based at the Rosenfeld Lab of the Cancer Research UK Cambridge Institute and at the Amsterdam UMC, and Dr Richard Mair, who is based at Cancer Research UK Cambridge Institute and the University of Cambridge developed two approaches in parallel to overcome the challenge of detecting brain tumour cfDNA.

The first approach works for patients who have previously had glioma removed and biopsied. The team designed a tumour-guided sequencing test that was able to look for the mutations found in the tumour tissue within the cfDNA in the patient’s urine, CSF, and blood plasma.

A total of eight patients who had suspected brain tumours based on MRIs were included in this part of the study. Samples were taken at their initial brain tumour biopsies, alongside CSF, blood and urine samples.

By knowing where in the DNA strand to look, the researchers found that it was possible to find mutations even in the tiny amounts of cfDNA found in the blood plasma and urine.

The test was able to detect cfDNA in 7 out of 8 CSF samples, 10 out of the 12 plasma blood samples and 10 out of the 16 urine samples.

For the second approach the researchers looked for other patterns in the cfDNA that could also indicate the presence of a tumour, without having to identify the mutations.

They analysed 35 samples from glioma patients, 27 people with non-malignant brain disorders, and 26 healthy people. They used whole genome sequencing, where all the cfDNA of the tumour is analysed, not just the mutations.

They found in the blood plasma and urine samples that fragments of cfDNA, which came from patients with brain tumours were different sizes than those from patients with no tumours in CSF. They then fed this data into a machine learning algorithm which was able to successfully differentiate between the urine samples of people with and without glioma.

The researchers say that while the machine learning test is cheaper and easier, and a tissue biopsy from the tumour is not needed, it is not as sensitive and is less specific than the first tumour-guided sequencing approach.

MRIs are not invasive or expensive, but they do require a trip to the hospital, and the three-month gap between checks can be a regular source of anxiety for patients.

The researchers suggest that their tests could be used between MRI scans, and could ultimately be able to detect a returning brain tumour earlier.

The next stage of this research will see the team comparing both tests against MRI scans in a trial with patients with brain tumours who are in remission to see if it can detect if their tumours are coming back at the same time or earlier than the MRI. If the tests prove that they can detect brain tumours earlier than an MRI, then the researchers will look at how they can adapt the tests so they could be offered in the clinic, which could be within the next ten years.

“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” said Mair. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”

Michelle Mitchell, Chief Executive of Cancer Research UK said, “While this is early research, it’s opened up the possibility that within the next decade we could be able to detect the presence of a brain tumour with a simple urine or blood test. Liquid biopsies are a huge area of research interest right now because of the opportunities they create for improved patient care and early diagnosis. It’s great to see Cancer Research UK researchers making strides in this important field.”

Sue Humphreys, from Wallsall, a brain tumour patient, said: "If these tests are found to be as accurate as the standard MRI for monitoring brain tumours, it could be life changing.

If patients can be given a regular and simple test by their GP, it may help not only detect a returning brain tumour in its earliest stages, it can also provide the quick reassurance that nothing is going on which is the main problem we all suffer from, the dreaded Scanxiety.

The problem with three-monthly scans is that these procedures can get disrupted by other things going on, such as what we have seen with the Covid pandemic. As a patient, this causes worry as there is a risk that things may be missed, or delayed, and early intervention is the key to any successful treatment.”

 

Reference:
Florent Mouliere et al. ‘Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients.’ EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202012881

Adapted from a Cancer Research UK press release.

Researchers from the Cancer Research UK Cambridge Institute have developed two tests that can detect the presence of glioma, a type of brain tumour, in patient urine or blood plasma.

Cancerdiagnosticbrainbrain tumourstumoursFlorent MouliereRichard MairCancer Research UK (CRUK)Cancer Research UK Cambridge InstituteSchool of Clinical Medicine


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Blushing plants reveal when fungi are growing in their roots

Fri, 23/07/2021 - 08:06

This is the first time this vital, 400 million year old process has been visualised in real time in full root systems of living plants. Understanding the dynamics of plant colonisation by fungi could help to make food production more sustainable in the future.

Almost all crop plants form associations with a particular type of fungi – called arbuscular mycorrhiza fungi – in the soil, which greatly expand their root surface area. This mutually beneficial interaction boosts the plant’s ability to take up nutrients that are vital for growth. 

The more nutrients plants obtain naturally, the less artificial fertilisers are needed. Understanding this natural process, as the first step towards potentially enhancing it, is an ongoing research challenge. Progress is likely to pay huge dividends for agricultural productivity.

In a study published in the journal PLOS Biology, researchers used the bright red pigments of beetroot – called betalains – to visually track soil fungi as they colonised plant roots in a living plant. 

“We can now follow how the relationship between the fungi and plant root develops, in real-time, from the moment they come into contact. We previously had no idea about what happened because there was no way to visualise it in a living plant without the use of elaborate microscopy,” said Dr Sebastian Schornack, a researcher at the University of Cambridge’s Sainsbury Laboratory and joint senior author of the paper. 

To achieve their results, the researchers engineered two model plant species – a legume and a tobacco plant – so that they would produce the highly visible betalain pigments when arbuscular mycorrhiza fungi were present in their roots. This involved combining the control regions of two genes activated by mycorrhizal fungi with genes that synthesise red-coloured betalain pigments.

The plants were then grown in a transparent structure so that the root system was visible, and images of the roots could be taken with a flatbed scanner without disturbing the plants.

Using their technique, the researchers could select red pigmented parts of the root system to observe the fungus more closely as it entered individual plant cells and formed elaborate tree-like structures – called arbuscules – which grow inside the plant’s roots. Arbuscules take up nutrients from the soil that would otherwise be beyond the reach of the plant. 

Other methods exist to visualise this process, but these involve digging up and killing the plant and the use of chemicals or expensive microscopy. This work makes it possible for the first time to watch by eye and with simple imaging how symbiotic fungi start colonising living plant roots, and inhabit parts of the plant root system over time.

“This is an exciting new tool to visualise this, and other, important plant processes. Beetroot pigments are a distinctive colour, so they’re very easy to see. They also have the advantage of being natural plant pigments, so they are well tolerated by plants,” said Dr Sam Brockington, a researcher in the University of Cambridge’s Department of Plant Sciences, and joint senior author of the paper.

Mycorrhiza fungi are attracting growing interest in agriculture. This new technique provides the ability to ‘track and trace’ the presence of symbiotic fungi in soils from different sources and locations. The researchers say this will enable the selection of fungi that colonise plants fastest and provide the biggest benefits in agricultural scenarios.

Understanding and exploiting the dynamics of plant root system colonisation by fungi has potential to enhance future crop production in an environmentally sustainable way. If plants can take up more nutrients naturally, this will reduce the need for artificial fertilisers – saving money and reducing associated water pollution. 

This research was funded by the Biotechnology and Biological Sciences Research Council, Gatsby Charitable Foundation, Royal Society, and Natural Environment Research Council. 

Reference
Timoneda, A. & Yunusov, T. et al: ‘MycoRed: Betalain pigments enable in vivo real-time visualisation of arbuscular mycorrhizal colonisation.’ PLOS Biology, July 2021. DOI: 10.1371/journal.pbio.3001326

Scientists have created plants whose cells and tissues ‘blush’ with beetroot pigments when they are colonised by fungi that help them take up nutrients from the soil.

plant sciencesGlobal food securitySustainable agricultureSustainable EarthSam BrockingtonSebastian SchornackCambridge University Botanic GardenDepartment of Plant SciencesSainsbury LaboratorySchool of the Biological SciencesWe can now follow how the relationship between the fungi and plant root develops, in real-time, from the moment they come into contact.Sebastian SchornackTemur Yunusov and Alfonso TimonedaCells of roots colonised by fungi turn red


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: AttributionNews type: News

Scientists reverse age-related memory loss in mice

Thu, 22/07/2021 - 15:18

In a study published in Molecular Psychiatry, the team show that changes in the extracellular matrix of the brain – ‘scaffolding’ around nerve cells – lead to loss of memory with ageing, but that it is possible to reverse these using genetic treatments.

Recent evidence has emerged of the role of perineuronal nets (PNNs) in neuroplasticity – the ability of the brain to learn and adapt – and to make memories. PNNs are cartilage-like structures that mostly surround inhibitory neurons in the brain. Their main function is to control the level of plasticity in the brain. They appear at around five years old in humans, and turn off the period of enhanced plasticity during which the connections in the brain are optimised. Then, plasticity is partially turned off, making the brain more efficient but less plastic.

PNNs contain compounds known as chondroitin sulphates. Some of these, such as chondroitin 4-sulphate, inhibit the action of the networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulphate, promote neuroplasticity. As we age, the balance of these compounds changes, and as levels of chondroitin 6-sulphate decrease, so our ability to learn and form new memories changes, leading to age-related memory decline.

Researchers at the University of Cambridge and University of Leeds investigated whether manipulating the chondroitin sulphate composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits.

To do this, the team looked at 20-month old mice – considered very old – and using a suite of tests showed that the mice exhibited deficits in their memory compared to six-month old mice.

For example, one test involved seeing whether mice recognised an object. The mouse was placed at the start of a Y-shaped maze and left to explore two identical objects at the end of the two arms. After a short while, the mouse was once again placed in the maze, but this time one arm contained a new object, while the other contained a copy of the repeated object. The researchers measured the amount of time the mouse spent exploring each object to see whether it had remembered the object from the previous task. The older mice were much less likely to remember the object.

The team treated the ageing mice using a ‘viral vector’, a virus capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs and found that this completely restored memory in the older mice, to a level similar to that seen in the younger mice.

Dr Jessica Kwok from the School of Biomedical Sciences at the University of Leeds said: “We saw remarkable results when we treated the ageing mice with this treatment. The memory and ability to learn were restored to levels they would not have seen since they were much younger.”

To explore the role of chondroitin 6-sulphate in memory loss, the researchers bred mice that had been genetically-manipulated such that they were only able to produce low levels of the compound to mimic the changes of ageing. Even at 11 weeks, these mice showed signs of premature memory loss. However, increasing levels of chondroitin 6-sulphate using the viral vector restored their memory and plasticity to levels similar to healthy mice.

Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge said: “What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents. This suggests that it may be possible to prevent humans from developing memory loss in old age.”

The team have already identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs. When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury. The researchers are investigating whether it might help alleviate memory loss in animal models of Alzheimer's disease.

The approach taken by Professor Fawcett’s team – using viral vectors to deliver the treatment – is increasingly being used to treat human neurological conditions. A second team at the Centre recently published research showing their use for repairing damage caused by glaucoma and dementia.

The study was funded by Alzheimer’s Research UK, the Medical Research Council, European Research Council and the Czech Science Foundation.

 

Reference
Yang, S et al. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Molecular Psychiatry; 16 July 2021; DOI: doi.org/10.1038/s41380-021-01208-9

Scientists at Cambridge and Leeds have successfully reversed age-related memory loss in mice and say their discovery could lead to the development of treatments to prevent memory loss in people as they age.

brainNeuroscienceageingneurodegenerationanimal researchJames FawcettUniversity of LeedsAlzheimer's Research UKEuropean Research CouncilMedical Research CouncilCzech Science FoundationJohn van Geest Centre for Brain RepairSchool of Clinical MedicineAlthough our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents. This suggests that it may be possible to prevent humans from developing memory loss in old ageJames FawcettMichael Shribak, Marine Biological Laboratory, Woods Hole, MASpatially oriented neurons (mouse brain)


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Attribution-NoncommericalNews type: News

Llama ‘nanobodies’ could hold key to preventing deadly post-transplant infection

Thu, 22/07/2021 - 10:07

Around four out of five people in the UK are thought to be infected with HCMV, and in developing countries this can be as high as 95%. For the majority of people, the virus remains dormant, hidden away inside white blood cells, where it can remain undisturbed and undetected for decades. If the virus reactivates in a healthy individual, it does not usually cause symptoms. However, for people who are immunocompromised – for example, transplant recipients who need to take immunosuppressant drugs to prevent organ rejection – HCMV reactivation can be devastating.

At present, there is no effective vaccine against HCMV, and anti-viral drugs often prove ineffective or have very serious side-effects.

Now, in a study published in Nature Communications, researchers at Vrije Universiteit Amsterdam in the Netherlands and at the University of Cambridge have found a way to chase the virus from its hiding place using a special type of antibody known as a nanobody.

Nanobodies were first identified in camels and exist in all camelids – a family of animals that also includes dromedary, llamas and alpacas. Human antibodies consist of two heavy and two light chains of molecules, which together recognise and bind to markers on the surface of a cell or virus known as antigens. For this special class of camelid antibodies, however, only a single fragment of the antibody – often referred to as single domain antibody or nanobody – is sufficient to properly recognize antigens.

Dr Timo De Groof from Vrije Universiteit Amsterdam, the study’s joint first author, said: “As the name suggests, nanobodies are much smaller than regular antibodies, which make them perfectly suited for particular types of antigens and relatively easy to manufacture and adjust. That’s why they’re being hailed as having the potential to revolutionise antibody therapies.”

The first nanobody has been approved and introduced onto the market by biopharmaceutical company Ablynx, while other nanobodies are already in clinical trials for diseases like rheumatoid arthritis and certain cancers. Now, the team in The Netherlands and the UK have developed nanobodies that target a specific virus protein (US28), one of the few elements detectable on the surface of a HCMV latently infected cell and a main driver of this latent state.

Dr Ian Groves from the Department of Medicine at the University of Cambridge said: “Our team has shown that nanobodies derived from llamas have the potential to outwit human cytomegalovirus. This could be very important as the virus can cause life-threatening complications in people whose immune systems are not functioning properly.”

In laboratory experiments using blood infected with the virus, the team showed that the nanobody binds to the US28 protein and interrupts the signals established through the protein that help keep the virus in its dormant state. Once this control is broken, the local immune cells are able to 'see' that the cell is infected, enabling the host’s immune cells to hunt down and kill the virus, purging the latent reservoir and clearing the blood of the virus.

Dr Elizabeth Elder, joint first author, who carried out her work while at the University of Cambridge, said: “The beauty of this approach is that it reactivates the virus just enough to make it visible to the immune system, but not enough for it to do what a virus normally does – replicating and spreading. The virus is forced to put its head above the parapet where it can then be killed by the immune system.”

Professor Martine Smit, also from from the Vrije Universiteit Amsterdam, added: “We believe our approach could lead to a much-needed new type of treatment for reducing – and potentially even preventing – CMV infectious in patients eligible for organ and stem cell transplants.”

The research was funded by the Dutch Research Council (NWO), Wellcome and the Medical Research Council, with support from the NIHR Cambridge Biomedical Research Centre.

 

Reference
De Groof TWM, Elder E, et al. Targeting the latent human cytomegalovirus reservoir for T-cell mediated killing with virus specific nanobodies. Nature Communications (2021). DOI: 10.1038/s41467-021-24608-5

Scientists have developed a ‘nanobody’ – a small fragment of a llama antibody – that is capable of chasing out human cytomegalovirus (HCMV) as it hides away from the immune system. This then enables immune cells to seek out and destroy this potentially deadly virus.

medicinevirologytransplantationInfectious diseasesElizabeth ElderIan GrovesVrije Universiteit AmsterdamDutch Research Council (NWO)WellcomeMedical Research CouncilDepartment of MedicineSchool of Clinical MedicineNIHR Cambridge Biomedical Research CentreOur team has shown that nanobodies derived from llamas have the potential to outwit human cytomegalovirusIan GrovesJessica Knowlden on UnsplashLlamas


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Biological ‘fingerprints’ of long COVID in blood could lead to diagnostic test, say Cambridge scientists

Mon, 19/07/2021 - 08:39

The team has received funding from the National Institute for Health Research to develop a test that could complement existing antibody tests. They also aim to use similar biological signatures to develop a test and monitor for long COVID.

While most people recover from COVID-19 in a matter of days or weeks, around one in ten people go on to develop symptoms that can last for several months. This can be the case irrespective of the severity of their COVID-19 – even individuals who were asymptomatic can experience so-called ‘long COVID’.

Diagnosing long COVID can be a challenge, however. A patient with asymptomatic or mild disease may not have taken a PCR test at the time of infection – the gold standard for diagnosing COVID-19 –  and so has never had a confirmed diagnosis.  Even antibody tests – which look for immune cells produced in response to infection – are estimated to miss around 30% of cases, particularly among those who have had only mild disease and or beyond six months post-initial illness.

A team at the University of Cambridge and Cambridge University Hospital NHS Foundation Trust has received £370,000 from the National Institute for Health Research to develop a COVID-19 diagnostic test that would complement existing antibody tests and a test that could objectively diagnose and monitor long COVID.

The research builds on a pilot project supported by the Addenbrooke’s Charitable Trust. The team has been recruiting patients from the Long COVID Clinic established in May 2020 at Addenbrooke’s Hospital, part of Cambridge University Hospital NHS Foundation Trust.

During the pilot, the team recruited 85 patients to the Cambridge NIHR COVID BioResource, which collects blood samples from patients when they are first diagnosed and then at follow-up intervals over several months. They now hope to expand their cohort to 500 patients, recruited from Cambridgeshire and Peterborough.

In their initial findings, the team identified a biomarker – a biological fingerprint – in the blood of patients who had previously had COVID-19. This biomarker is a molecule known as a cytokine produced by T cells in response to infection. As with antibodies, this biomarker persists in the blood for a long time after infection. The team plans to publish their results shortly.

Dr Mark Wills from the Department of Medicine at the University of Cambridge, who co-leads the team, said: “We need a reliable and objective way of saying whether someone has had COVID-19. Antibodies are one sign we look for, but not everyone makes a very strong response and this can wane over time and become undetectable.

“We’ve identified a cytokine that is also produced in response to infection by T cells and is likely to be detectable for several months – and potentially years – following infection. We believe this will help us develop a much more reliable diagnostic for those individuals who did not get a diagnosis at the time of infection.”

By following patients for up to 18 months post-infection, the team hopes to address several questions, including whether immunity wanes over time. This will be an important part of helping understand whether people who have been vaccinated will need to receive boosters to keep them protected.

As part of their pilot study, the team also identified a particular biomarker found in patients with long COVID. Their work suggests these patients produce a second type of cytokine, which persists in patients with long COVID compared to those that recover quickly and might be one of the drivers behind the many symptoms that patients experience. This might therefore prove to be useful for diagnosing long COVID.

Dr Nyarie Sithole, also from the Department of Medicine at the University of Cambridge, who co-leads the team and helps to manage long COVID patients, said:  “Because we currently have no reliable way of diagnosing long COVID, the uncertainty can cause added stress to people who are experiencing potential symptoms. If we can say to them ‘yes, you have a biomarker and so you have long COVID’, we believe this will help allay some of their fears and anxieties.

“There is anecdotal evidence that patients see an improvement in symptoms of long COVID once they have been vaccinated – something that we have seen in a small number of patients in our clinic. Our study will allow us to see how this biomarker changes over a longer period of time in response to vaccination.”

At the moment, the team is using the tests for research purposes, but by increasing the size of their study cohort and carrying out further work, they hope to adapt and optimise the tests that can be scaled up and speeded up, able to be used by clinical diagnostic labs.

As well as developing a reliable test, the researchers hope their work will help provide an in-depth understanding of how the immune system responds to coronavirus infection – and why it triggers long COVID in some people.

Dr Sithole added: “One of the theories of what’s driving long COVID is that it’s a hyperactive immune response – in other words, the immune system switches on at the initial infection and for some reason never switches off or never goes back to the baseline. As we’ll be following our patients for many months post-infection, we hope to better understand whether this is indeed the case.”

In addition, having a reliable biomarker could help in the development of new treatments against COVID. Clinical trials require an objective measure of whether a drug is effective. Changes in – or the disappearance of – long-COVID-related cytokine biomarkers with corresponding symptom improvement in response to drug treatment would suggest that a treatment intervention is working.

Markers in our blood – ‘fingerprints’ of infection – could help identify individuals who have been infected by SARS-CoV-2, the coronavirus that causes COVID-19, several months after infection even if the individual had only mild symptoms or showed no symptoms at all, say Cambridge researchers.

COVID-19CoronavirusdiagnosticInfectious diseasesimmunologyNyarie SitholeMark WillsNational Institute for Health Research (NIHR)School of Clinical MedicineDepartment of MedicineCambridge University Hospitals NHS Foundation TrustAddenbrooke's HospitalCambridge Infectious DiseasesBecause we currently have no reliable way of diagnosing long COVID, the uncertainty can cause added stress to people who are experiencing potential symptoms. If we can say to them ‘yes, you have a biomarker and so you have long COVID’, we believe this will help allay some of their fears and anxietiesNyarie SitholeAnnie SprattTired looking woman


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News

University of Cambridge launches roadmap to support future growth of life sciences cluster

Fri, 16/07/2021 - 10:49

The roadmap sets out a clear plan to create a bridge between two of Cambridge’s historical strengths — biomedical research and cutting-edge technology — and bring these specialisms together to develop new treatments and health tech with real world applications. The solutions in the roadmap are scalable beyond Cambridge and also applicable to other disciplines and sectors.

Professor Andy Neely, Pro-Vice-Chancellor for Enterprise and Business Relations at the University of Cambridge, said: “Cambridge has a deep and rich history of discovery and collaboration, and its interdisciplinary environment is the perfect testbed for new models of innovation in the life sciences. Our roadmap sets out a plan to do just that and will ensure that Cambridge remains a global leader in health technology into the next generation.

“This will require us to pioneer new ways of working and creating connections between different institutions across disciplines, be they academic or private enterprise. Such a model has been proven to work at a small scale – our proposal in the roadmap is to scale this up and apply it across the cluster and beyond.”

The University sits at the heart of the so-called ‘Cambridge cluster’, in which more than 5,300 knowledge-intensive firms employ more than 67,000 people and generate £18 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK.

The mission of the University is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. This includes cultivating and delivering excellent research and world-leading innovation and training of the next generation of highly skilled researchers and entrepreneurs, thereby underpinning the UK's economic growth and competitiveness.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute at the University of Cambridge, said: “The pandemic has clearly shown the importance of rapid innovation in healthcare. We are determined to harness the power of innovation, creativity and collaboration in Cambridge, and apply this towards solving some of the biggest medical challenges facing the country, and the world.”

The Connect: Health Tech roadmap is a result of consultation with major stakeholders and a series of road-mapping workshops with the Cambridge community. It aims to shape the future success of the Cambridge cluster in health tech through a supportive and dynamic ecosystem that aligns with the needs of the community.

The roadmap includes ambitious steps to build strong foundations for the Cambridge cluster for the next 20 years and will support the region's economic recovery post-pandemic and bring cutting-edge research, businesses and innovators together to be better prepared and connected for the future. Connect: Health Tech will also increase access to the Cambridge ecosystem extending reach and helping to level up growth and investment across the East of England and the Oxford-Cambridge Arc.

One of the major recommendations in the report is to create and foster connectivity at the interface between medicine and technology and across sectors. This recommendation has been piloted by expanding the Cambridge cluster from a physical community to a digital one.

The COVID19 pandemic has required the creation of an innovative model of access and navigation to Cambridge. The digital platform simplifies navigation of the Cambridge research community and enables new companies based all over the world to access expertise and knowledge across the University with the aim of increasing inward investment in the life sciences. It also pilots an approach to navigation and connectivity that can be scaled up across the Arc and the UK. This new way of working will speed up the development of new healthcare innovations and technologies that the NHS will use in years to come.

Connect: Health Tech is a Cambridge University initiative funded by Research England. Connect: Health Tech UEZ has been created to build a highly effective interdisciplinary bridge between two Cambridge research hubs and beyond: the West science and technology hub anchored at the Maxwell Centre and South biomedical hub anchored at the Milner Therapeutics Institute. The bridge will bring together and integrate a community from across the University, research institutes, NHS, industry, investors, local and national Government, with a focus on medtech, digital health and therapeutics, to create opportunities that will transform ideas at the interface between medicine and technology into reality.

Read Creating a University Enterprise Zone for Cambridge across the life and physical sciences

Connect: Health Tech, the University of Cambridge Enterprise Zone, has today launched a roadmap, ‘Creating a University Enterprise Zone for Cambridge across the life and physical sciences’, that examines the challenges faced in futureproofing and sustaining the growth of the life sciences cluster to maintain Cambridge as a global centre of excellence for health tech.

Innovationspotlight on innovationenterpriseAndy NeelyTony KouzaridesCambridge Biomedical CampusSchool of Clinical MedicineMilner Therapeutics InstituteCambridge has a deep and rich history of discovery and collaboration, and its interdisciplinary environment is the perfect testbed for new models of innovation in the life sciencesAndy NeelyAstraZenecaCambridge Biomedical Campus


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Top UK organisations release annual statistics for use of animals in research

Thu, 15/07/2021 - 10:07

This is to coincide with the Home Office’s publication of Great Britain’s statistics for animals used in research in 2020.

These ten organisations carried out 1,343,893 procedures, 47% or nearly half of the 2,883,310 procedures carried out in Great Britain in 2020. More than 99% of these 1,343,893 procedures were carried out in rodents or fish.

The statistics are freely available on the organisations’ websites as part of their ongoing commitment to transparency and openness around the use of animals in research.

The ten organisations are listed below alongside the total number of procedures that they carried out in 2020. This is the sixth consecutive year organisations have come together to publicise their collective statistics and examples of their research.

Organisation Number of Procedures The Francis Crick Institute 183,811 University of Cambridge 177,219 Medical Research Council 173,637 University of Oxford 169,511 University of Edinburgh 151,669 UCL 142,988 University of Glasgow 102,526 University of Manchester 93,448 King's College London 85,414 Imperial College London 63,670 TOTAL 1,343,893

A further breakdown of Cambridge’s numbers, including the number of procedures by species and detail of the levels of severity, can be found on our animal research pages.

Animal research has been essential for developing lifesaving vaccines and treatments for Covid-19. Ferrets and macaque monkeys were used to test the safety and efficacy of Covid-19 vaccines, including the successful Oxford / AstraZeneca vaccine. Hamsters are being used to develop Covid-19 treatment strategies as they display a more severe form of the disease than ferrets and monkeys. Guinea pigs have also been used in regulatory research to batch test vaccine potency.

Despite all this research to develop vaccines and treatments for Covid-19, the majority of UK research facilities carried out significantly less research than usual due to the various national lockdowns. Therefore, the 2020 figures cannot be reasonably compared with previous statistics.

All organisations are committed to the ‘3Rs’ of replacement, reduction and refinement. This means avoiding or replacing the use of animals where possible; minimising the number of animals used per experiment and optimising the experience of the animals to improve animal welfare. However, as institutions expand and conduct more research, the total number of animals used can rise even if fewer animals are used per study.

All organisations listed are signatories to the Concordat on Openness on Animal Research in the UK, a commitment to be more open about the use of animals in scientific, medical and veterinary research in the UK. More than 120 organisations have signed the Concordat including UK universities, medical research charities, research funders, learned societies and commercial research organisations.

Wendy Jarrett, Chief Executive of Understanding Animal Research, which developed the Concordat on Openness, said:

"Animal research has been essential to the development and safety testing of lifesaving COVID-19 vaccines and treatments. Macaque monkeys and ferrets have been used to develop vaccines, including the Oxford / AstraZeneca vaccine, hamsters are being used to develop treatments, and guinea pigs are used to quality-check each batch of vaccines.

"Animal testing provided scientists with initial data that the vaccines were effective and safe enough to move into human clinical trials. During these trials, thousands more humans than animals were used to test how effective and safe the vaccines were in people. The pandemic has led to increased public interest in the way vaccines and medicines are developed and UAR has worked with research institutions and funding bodies throughout the UK to develop resources that explain to the public how animals have been used in this critical research."

University of Cambridge Establishment Licence Holder Dr Martin Vinnell said:

“Animal research currently plays an essential role in our understanding of health and disease and in the development of modern medicines and surgical techniques. Without the use of animals, we would not have many of the modern medicines, antibiotics, vaccines and surgical techniques we take for granted in both human and veterinary medicine.

“We always aim to use as few animals as possible, refining our research and actively looking for ways of replacing their use, for example in the development of ‘mini-organs’ grown from human cells, which can be used to model disease.”

Adapted from a press release by Understanding Animal Research.

  Find out more

A team in the University of Cambridge’s Department of Engineering is developing implantable devices to bypass nerve damage and restore movement to paralysed limbs.

“Our aim is to make muscles wireless by intercepting electrical signals from the brain before they enter the damaged nerve and sending them directly to the target muscles via radio waves,” says Sam Hilton, a Research Assistant in the team.

The procedure has been tested and refined in computer simulations, and on cells grown in the lab. But before it can be tested in humans there is another important step: testing its safety in living rats. To avoid testing in animals entirely would place untenable risk on the first human recipients of this new device. All the experiments are carefully designed to ensure that just enough animals are used to produce convincing data, without resulting in unnecessary excess.

By working out how complex microelectronics can interface with living tissue in a very precise and controlled way, this work has potential to improve or restore movement in patients suffering severe nerve damage - improving their quality of life and easing the burden on our healthcare services.

The ten organisations in Great Britain that carry out the highest number of animal procedures – those used in medical, veterinary and scientific research - have today released their annual statistics.

animal researchUnderstanding Animal ResearchSchool of Clinical MedicineSchool of Biological SciencesWe always aim to use as few animals as possible, refining our research and actively looking for ways of replacing their use. Martin Vinnell


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Climate changed the size of our bodies and, to some extent, our brains

Thu, 08/07/2021 - 10:21

An interdisciplinary team of researchers, led by the Universities of Cambridge and Tübingen, has gathered measurements of body and brain size for over 300 fossils from the genus Homo found across the globe. By combining this data with a reconstruction of the world’s regional climates over the last million years, they have pinpointed the specific climate experienced by each fossil when it was a living human.

The study reveals that the average body size of humans has fluctuated significantly over the last million years, with larger bodies evolving in colder regions. Larger size is thought to act as a buffer against colder temperatures: less heat is lost from a body when its mass is large relative to its surface area. The results are published today in the journal Nature Communications.

Our species, Homo sapiens, emerged around 300,000 years ago in Africa. The genus Homo has existed for much longer, and includes the Neanderthals and other extinct, related species such as Homo habilis and Homo erectus.

A defining trait of the evolution of our genus is a trend of increasing body and brain size; compared to earlier species such as Homo habilis, we are 50% heavier and our brains are three times larger. But the drivers behind such changes remain highly debated.

“Our study indicates that climate - particularly temperature - has been the main driver of changes in body size for the past million years,” said Professor Andrea Manica, a researcher in the University of Cambridge’s Department of Zoology who led the study.

He added: “We can see from people living today that those in warmer climates tend to be smaller, and those living in colder climates tend to be bigger. We now know that the same climatic influences have been at work for the last million years.”

The researchers also looked at the effect of environmental factors on brain size in the genus Homo, but correlations were generally weak. Brain size tended to be larger when Homo was living in habitats with less vegetation, like open steppes and grasslands, but also in ecologically more stable areas. In combination with archaeological data, the results suggest that people living in these habitats hunted large animals as food - a complex task that might have driven the evolution of larger brains.

“We found that different factors determine brain size and body size – they’re not under the same evolutionary pressures. The environment has a much greater influence on our body size than our brain size,” said Dr Manuel Will at the University of Tubingen, Germany, first author of the study.

He added: “There is an indirect environmental influence on brain size in more stable and open areas: the amount of nutrients gained from the environment had to be sufficient to allow for the maintenance and growth of our large and particularly energy-demanding brains.”

This research also suggests that non-environmental factors were more important for driving larger brains than climate, prime candidates being the added cognitive challenges of increasingly complex social lives, more diverse diets, and more sophisticated technology.

The researchers say there is good evidence that human body and brain size continue to evolve. The human physique is still adapting to different temperatures, with on average larger-bodied people living in colder climates today. Brain size in our species appears to have been shrinking since the beginning of the Holocene (around 11,650 years ago). The increasing dependence on technology, such as an outsourcing of complex tasks to computers, may cause brains to shrink even more over the next few thousand years.

“It’s fun to speculate about what will happen to body and brain sizes in the future, but we should be careful not to extrapolate too much based on the last million years because so many factors can change,” said Manica.

This research was funded by the European Research Council and the Antarctic Science Platform.

Reference

Will, M. et al: ‘Different environmental variables predict body and brain size evolution in Homo.’ Nature Communications, July 2021. DOI: 10.1038/s41467-021-24290-7

The average body size of humans has fluctuated significantly over the last million years and is strongly linked to temperature. Colder, harsher climates drove the evolution of larger body sizes, while warmer climates led to smaller bodies. Brain size also changed dramatically but did not evolve in tandem with body size.

evolutionClimate changeAndrea ManicaUniversity of TübingenDepartment of ZoologyClare CollegeSchool of the Biological SciencesOur study indicates that climate - particularly temperature - has been the main driver of changes in body size for the past million years.Andrea ManicaHuman fossils illustrating the variation in brain (skulls) and body size (thigh bones) during the Pleistocene.


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Rare genetic variants confer largest increase in type 2 diabetes risk seen to date

Wed, 07/07/2021 - 12:10

Type 2 diabetes is thought to be driven in part by inherited genetic factors, but many of these genes are yet unknown. Previous large-scale studies have depended on efficient ‘array genotyping’ methods to measure genetic variations across the whole genome. This approach typically does a good job at capturing the common genetic differences between people, though individually these each confer only small increases in diabetes risk.

Recent technical advances have allowed more comprehensive genetic measurement by reading the complete DNA sequences of over 20,000 genes that code for proteins in humans. Proteins are essential molecules that enable our bodies to function. In particular, this new approach has allowed for the first time a large-scale approach to study the impact of rare genetic variants on several diseases, including type 2 diabetes.

By looking at data from more than 200,000 adults in the UK Biobank study, researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge used this approach to identify genetic variants associated with the loss of the Y chromosome. This is a known biomarker of biological ageing that occurs in a small proportion of circulating white blood cells in men and indicates a weakening in the body’s cellular repair systems. This biomarker has been previously linked to age-related diseases such as type 2 diabetes and cancer.

In results published today in Nature Communications, the researchers identified rare variants in the gene GIGYF1 that substantially increase susceptibility to loss of the Y chromosome, and also increase an individual’s risk of developing type 2 diabetes six-fold. In contrast, common variants associated with type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold.

Around 1 in 3,000 individuals carries such a GIGYF1 genetic variant. Their risk of developing type 2 diabetes is around 30%, compared to around 5% in the wider population. In addition, people who carried these variants had other signs of more widespread ageing, including weaker muscle strength and more body fat.

GIGYF1 is thought to control insulin and cell growth factor signalling. The researchers say their findings identify this as a potential target for future studies to understand the common links between metabolic and cellular ageing, and to inform future treatments.

Dr John Perry, from the MRC Epidemiology Unit and a senior author on the paper, said: “Reading an individual’s DNA is a powerful way of identifying genetic variants that increase our risk of developing certain diseases. For complex diseases such as type 2 diabetes, many variants play a role, but often only increasing our risk by a tiny amount. This particular variant, while rare, has a big impact on an individual’s risk.”

Professor Nick Wareham, Director of the MRC Epidemiology Unit, added: “Our findings highlight the exciting scientific potential of sequencing the genomes of very large numbers of people. We are confident that this approach will bring a rich new era of informative genetic discoveries that will help us better understand common diseases such as type 2 diabetes. By doing this, we can potentially offer better ways to treat – or even to prevent – the condition.”

Ongoing research will aim to understand how the loss of function variants in GIGYF1 lead to such a substantial increase in the risk of developing type 2 diabetes. Their future research will also examine other links between biomarkers of biological ageing in adults and metabolic disorders.

The research was funded by the Medical Research Council. UK Biobank is supported Wellcome, the Medical Research Council, British Heart Foundation, Cancer Research UK, Department of Health, Northwest Regional Development Agency and the Scottish Government.

Reference
Zhao, Y. et al. GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health. Nature Communications 2021; 07 Jul 2021; DOI: 10.1038/s41467-021-24504-y

Scientists at the University of Cambridge have identified rare genetic variants – carried by one in 3,000 people – that have a larger impact on the risk of developing type 2 diabetes than any previously identified genetic effect.

Spotlight on public healthPublic healthtype 2 diabetesdiabetesgeneticsGenomicsJohn PerryNick WarehamMedical Research CouncilUK BiobankWellcomeCancer Research UK (CRUK)British Heart FoundationDepartment of HealthNorthwest Regional Development AgencyScottish GovernmentSchool of Clinical MedicineMedical Research Council (MRC) Epidemiology UnitFor complex diseases such as type 2 diabetes, many variants play a role [in disease risk], but often only increasing our risk by a tiny amount. This particular variant, while rare, has a big impact on an individual’s riskJohn PerryqimonoDNA jigsaw


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News

Autistic individuals may be more likely to use recreational drugs to self-medicate their mental health

Thu, 01/07/2021 - 23:30

There is significant debate about substance use of autistic adolescents and adults. Some studies indicate that autistic individuals are less likely to use substances, whereas others suggest that autistic individuals are at greater risk of substance misuse or abuse. The team at the Autism Research Centre in Cambridge used a ‘mixed methods’ design to consider both the frequency of substance use among autistic individuals, as well as their self-reported experiences of substance use.

Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about the frequency of their substance use via an anonymous, online survey; of this group, 919 individuals also gave more in-depth responses about their experiences of substance use.

Autistic adults were less likely than non-autistic peers to use substances. Only 16% of autistic adults, compared to 22% of non-autistic adults, reported drinking on three or more days per week on average. Similarly, only 4% of autistic adults reported binge-drinking compared to 8% of non-autistic adults.

There were also some sex differences in patterns of substance use: autistic males were less likely than non-autistic males to report ever having smoked or used drugs. In contrast, the team did not find differences in the patterns of frequency of smoking or drug use between autistic and non-autistic females.

However, despite lower rates of substance use overall, the qualitative findings of the study provide a much less hopeful picture: autistic adults were nearly nine times more likely than non-autistic peers to report using recreational drugs (such as marijuana, cocaine and amphetamines)  to manage unwanted symptoms, including autism-related symptoms.

Drugs were used to reduce sensory overload, help with mental focus, and provide routine, among other reasons. Several autistic participants also indirectly referenced using substances to mask their autism. Past research has shown that this behavioural management (also known as ‘camouflaging’ or ‘compensating’) has been linked to emotional exhaustion, worse mental health, and even increased risk of suicide among autistic adults.

Autistic adolescents and adults were also over three times more likely than others to report using substances to manage mental health symptoms, including anxiety, depression, and suicidal thoughts. Several participants specifically noted that they used drugs for self-medication. However, this self-medication was not always viewed as negative by participants, and several noted that using recreational drugs allowed them to reduce the doses of prescribed medications for mental health conditions, which was a welcome change due to the sometimes significant side effects from their prescribed medications.

Another area of concern was the strong association between vulnerability and substance use among autistic teenagers and adults. Previous work from the Cambridge team suggests that autistic adults may be much more likely to have adverse life experiences and be at greater risk of suicide than others. The findings of the new study indicate that autistic individuals are over four times more likely to report vulnerability associated with substance use compared to their non-autistic peers, including dependence/addiction, using drugs to deal with past trauma, and substance use associated with suicide.

In addition, the study identified two new areas of vulnerability not been previously reported: being forced, tricked, or accidentally taking drugs; and childhood use of substances (at the age of 12 years or younger).

Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, and the lead researcher of the study, said: “Whether or not the substances currently classed as ‘recreational’ could be used medically remains an open question. It is evident that the current systems of health and social care support are not meeting the needs of many autistic teenagers and adults.

“No one should feel that they need to self-medicate for these issues without guidance from a healthcare professional. Identifying new forms of effective support is urgent considering the complex associations between substance use, mental health, and behaviour management—particularly as camouflaging and compensating behaviours are associated with suicide risk among autistic individuals.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “While some of our results suggest lower likelihood of substance use overall, physicians should not assume that their autistic patients aren’t using drugs. Drug use can be harmful so healthcare providers should aim to establish trusting relationships with autistic and non-autistic patients alike to foster frank and honest conversations about substance use.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “We continue to see new areas in which autistic adults experience vulnerability: mental health, physical health, suicide risk, lifestyle patterns, the criminal justice system, and so on. Substance use is now another area that we need to consider when developing new forms of support for autistic individuals. It is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this mark.”

The research was funded by the Autism Research Trust, Rosetrees Trust, Cambridge and Peterborough NHS Foundation Trust, Corbin Charitable Trust, Medical Research Council, Wellcome and the Innovative Medicines Initiative.

Reference
Weir, E., Allison, C., & Baron-Cohen, S. Understanding the substance use of autistic adolescents and adults: a mixed methods approach. The Lancet Psychiatry (2021).

While autistic individuals are less likely to use substances, those who do so are more likely to self-medicate for their mental health symptoms, according to new research from the University of Cambridge and published today in The Lancet Psychiatry.

Spotlight on neuroscienceNeuroscienceautismdrugsElizabeth WeirSimon Baron-CohenCarrie AllisonAutism Research TrustRosetrees TrustCambridge and Peterborough NHS Foundation TrustCorbin Charitable TrustMedical Research CouncilWellcomeInnovative Medicines InitiativeSchool of Clinical MedicineAutism Research CentreIt is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this markSimon Baron-CohenGRAS GRÜNMan smoking


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News

Scientists identify 160 new drugs that could be repurposed against COVID-19

Wed, 30/06/2021 - 19:00

In a study published today in Science Advances, a team led by researchers at the University of Cambridge’s Milner Therapeutics Institute and Gurdon Institute used a combination of computational biology and machine learning to create a comprehensive map of proteins that are involved in SARS-CoV-2 infection – from proteins that help the virus break into the host cell to those generated as a consequence of infection. By examining this network using artificial intelligence (AI) approaches, they were able to identify key proteins involved in infection as well as biological pathways that might be targeted by drugs.

To date, the majority of small molecule and antibody approaches for treating COVID-19 are drugs that are either currently the subject of clinical trials or have already been through clinical trials and been approved. Much of the focus has been on several key virus or host targets, or on pathways – such as inflammation – where a drug treatment could be used as an intervention.

The team used computer modelling to carry out a ‘virtual screen’ of almost 2,000 approved drugs and identified 200 approved drugs that could be effective against COVID-19. Forty of these drugs have already entered clinical trials, which the researchers argue supports the approach they have taken.

When the researchers tested a subset of those drugs implicated in viral replication, they found that two in particular – an antimalarial drug and a type of medicine used to treat rheumatoid arthritis – were able to inhibit the virus, providing initial validation of their data-driven approach.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute, who led the study, said: “By looking across the board at the thousands of proteins that play some role in SARS-CoV-2 infection – whether actively or as a consequence of infections – we’ve been able to create a network uncovering the relationship between these proteins.

“We then used the latest machine learning and computer modelling techniques to identify 200 approved drugs that might help us treat COVID-19. Of these, 160 had not been linked to this infection before. This could give us many more weapons in our armoury to fight back against the virus.”

Using artificial neural network analysis, the team classified the drugs depending on the overarching role of their targets in SARS-CoV-2 infection: those that targeted viral replication and those that targeted the immune response. They then took a subset of those involved in viral replication and tested them using cell lines derived from humans and from non-human primates.

Of particular note were two drugs, sulfasalazine (used to treat conditions such as rheumatoid arthritis and Crohn’s disease) and proguanil (and antimalarial drug), which the team showed reduced SARS-CoV-2 viral replication in cells, raising the possibility of their potential use to prevent infection or to treat COVID-19.

Dr Namshik Han, Head of Computational Research and AI at the Milner Therapeutics Institute, added: “Our study has provided us with unexpected information about the mechanisms underlying COVID-19 and has provided us with some promising drugs that might be repurposed for either treating or preventing infection. While we took a data-driven approach – essentially allowing artificially intelligent algorithms to interrogate datasets – we then validated our findings in the laboratory, confirming the power of our approach.

“We hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemics.”

The research was funded by LifeArc, the LOEWE Center DRUID, the Bundesministerium für Bildung und Forschung, the European Union’s Horizon 2020 programme, Wellcome and Cancer Research UK.

Reference
Han, N, Hwang, W, Tzelepis, K, & Schmerer, P, et al. Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies. Sci Adv; 30 June 2021

Cambridge scientists have identified 200 approved drugs predicted to work against COVID-19 – of which only 40 are currently being tested in COVID-19 clinical trials.

COVID-19Coronavirusdrug discoveryArtificial intelligencespotlight on future therapeuticsFuture therapeuticsTony KouzaridesNamshik HanLifeArcLOEWE Center DRUIDBundesministerium für Bildung und ForschungEuropean Union Horizon 2020WellcomeCancer Research UK (CRUK)School of Clinical MedicineMilner Therapeutics InstituteWellcome Trust-CRUK Gurdon InstituteWe hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemicsNamshik HangeraltGraphical representation of COVID-19 and networks


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News

Upgrading PPE for staff working on COVID-19 wards cut hospital-acquired infections dramatically

Tue, 29/06/2021 - 08:20

The findings are reported by a team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust. The research has not yet been peer-reviewed, but is being released early because of the urgent need to share information relating to the pandemic.

Until recently, advice from Public Health England recommended that healthcare workers caring for patients with COVID-19 should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment; if aerosol-generating procedures were being carried out (for example inserting a breathing tube into the patient’s windpipe), then the guidance recommended the use of an FFP3 respirator. PHE has recently updated its guidance to oblige NHS organisations to assess the risk that COVID-19 poses to staff and provide FFP3 respirators where appropriate.

Since the start of the pandemic, CUH has been screening its healthcare workers regularly for SARS-CoV-2, even where they show no symptoms. They found that healthcare workers caring for patients with COVID-19 were at a greater risk of infection than staff on non-COVID-19 wards, even when using the recommended respiratory protective equipment. As a result, its infection control committee implemented a change in respiratory protective equipment for staff on COVID-19 wards, from FRSMs to FFP3 respirators.

Prior to the change in respiratory protective equipment, cases were higher on COVID-19 wards compared with non-COVID-19 wards in seven out of the eight weeks analysed by the team. Following the change in protective equipment, the incidence of infection on the two types of ward was similar.

The results suggest that almost all cases among healthcare workers on non-COVID-19 wards were caused by community-acquired infection, whereas cases among healthcare workers on COVID-19 wards were caused by both community-acquired infection and direct, ward-based infection from patients with COVID-19 – but that these direct infections were effectively mitigated by the use of FFP3 respirators.

To calculate the risk of infection for healthcare workers working on COVID-19 and non-COVID-19 wards, the researchers developed a simple mathematical model.

Dr Mark Ferris from the University of Cambridge’s Occupational Health Service, one of the study’s authors, said: “Healthcare workers – particularly those working on COVID-19 wards – are much more likely to be exposed to coronavirus, so it’s important we understand the best ways of keeping them safe.

“Based on data collected during the second wave of the SARS-CoV-2 pandemic in the UK, we developed a mathematical model to look at the risks faced by those staff dealing with COVID-19 patients on a day to day basis. This showed us the huge effect that using better PPE could have in reducing the risk to healthcare workers.”

According to their model, the risk of direct infection from working on a non-COVID-19 ward was low throughout the study period, and consistently lower than the risk of community-based exposure.

By contrast, the risk of direct infection from working on a COVID-19 ward before the change in respiratory protective equipment was considerably higher than the risk of community-based exposure: staff on COVID-19 wards were at 47 times greater risk of acquiring infection while on the ward than staff working on a non-COVID-19 ward.

Crucially, however, the model showed that the introduction of FFP3 respirators provided up to 100% protection against direct, ward-based COVID-19 infection.

Dr Chris Illingworth from the MRC Biostatistics Unit at the University of Cambridge, said: “Before the face masks were upgraded, the majority of infections among healthcare workers on the COVID-19 wards were likely due to direct exposure to patients with COVID-19.

“Once FFP3 respirators were introduced, the number of cases attributed to exposure on COVID-19 wards dropped dramatically – in fact, our model suggests that FFP3 respirators may have cut ward-based infection to zero.”

Dr Nicholas Matheson from the Department of Medicine at the University of Cambridge, said: “Although more research will be needed to confirm our findings, we recommend that, in accordance with the precautionary principle, guidelines for respiratory protective equipment are further revised until more definitive information is available.”

Dr Michael Weekes from the Department of Medicine at the University of Cambridge, added: “Our data suggest there’s an urgent need to look at the PPE offered to healthcare workers on the frontline. Upgrading the equipment so that FFP3 masks are offered to all healthcare workers caring for patients with COVID-19 could reduce the number of infections, keep more hospital staff safe and remove some of the burden on already stretched healthcare services caused by absence of key staff due to illness. Vaccination is clearly also an absolute priority for anyone who hasn’t yet taken up their offer.”

The research was funded by Wellcome, the Addenbrooke’s Charitable Trust, UK Research and Innovations, and the NIHR Cambridge Biomedical Research Centre.

Reference
Ferris, M, Ferris, R et al. FFP3 respirators protect healthcare workers against infection with SARS-CoV-2. DOI: 10.22541/au.162454911.17263721/v1

When Addenbrooke’s Hospital in Cambridge upgraded its face masks for staff working on COVID-19 wards to filtering face piece 3 (FFP3) respirators, it saw a dramatic fall – up to 100% – in hospital-acquired SARS-CoV-2 infections among these staff.

COVID-19CoronavirushealthcareNational Health Service (NHS)Mark FerrisMichael WeekesNicholas MathesonWellcomeNational Institute for Health Research (NIHR)UK Research and Innovation (UKRI)Addenbrooke’s Charitable TrustSchool of Clinical MedicineDepartment of MedicineMedical Research Council (MRC) Biostatistics UnitAddenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustHealthcare workers – particularly those working on COVID-19 wards – are much more likely to be exposed to coronavirus, so it’s important we understand the best ways of keeping them safeMark FerrisCambridge University Hospitals NHS Foundation TrustHealthcare worker wearing FFP3 mask


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Key mutations in Alpha variant enable SARS-CoV-2 to overcome evolutionary weak points

Tue, 29/06/2021 - 08:00

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation - the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Now, in research published in the journal Cell Reports, researchers show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

The research was led by scientists at the University of Cambridge, MRC-University of Glasgow Centre for Virus Research, The Pirbright Institute, MRC Laboratory of Molecular Biology, and Vir Biotechnology.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, the study’s senior author, said: “Although we first saw this mutation in an immunocompromised patient and then in the Kent – now ‘Alpha’ – variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently.”

Working under secure conditions, Professor Gupta and colleagues used a harmless form of the virus that displays SARS-CoV-2 spike proteins with the H69/V70 deletion to understand how the spike protein interacts with host cells and what makes this mutation so important.

When they tested this virus against blood sera taken from fifteen individuals who had recovered from infection, they found that the deletion did not allow the virus to ‘escape’ neutralising antibodies made after being vaccinated or after previous infection. Instead, the team found that the deletion makes the virus twice as infective – that is, at breaking into the host’s cells – as a virus that dominated global infections during the latter half of 2020. This was because virus particles carrying the deletion had a greater number of mature spike proteins on their surface. This allows the virus to then replicate efficiently even when it has other mutations that might otherwise hinder the virus. 

“When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate,” said Professor Gupta.

“What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response. In other words, the deletion allowed these variants to have their cake and eat it – they were both better at escaping immunity and more infectious.”

Dr Dalan Bailey from The Pirbright Institute, who co-led the research, added: “In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread.”

Bo Meng from the Department of Medicine at the University of Cambridge, first author on the paper, said: “Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on.”

The research was supported by Wellcome, the Medical Research Council, the Bill & Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Reference
Meng, B, Kemp, SA, Papa, G, Datir R, Ferreira, IATM et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role 1 in the variant of concern lineage B.1.1.7. Cell Reports; 8 June 2021; DOI: 10.1016/j.celrep.2021.109292 

One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

COVID-19CoronavirusInfectious diseasesRavindra GuptaBo MengWellcomeMedical Research CouncilBill and Melinda Gates FoundationNational Institute for Health Research (NIHR)School of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Department of MedicineCambridge Fights COVIDNIHR Cambridge Biomedical Research CentreCambridge Infectious DiseasesUnderstanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early onBo MengKevin GrieveMan walking past Stay Alert/Save Lives artwork


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News

Inflatable, shape-changing spinal implants could help treat severe pain

Fri, 25/06/2021 - 18:14
Shorthand Story: FyBP8cXEaZShorthand Story Head: Inflatable, shape-changing spinal implants could help treat severe pain a{display:block;-webkit-transition:opacity .15s ease;transition:opacity .15s ease}.Theme-LinkedMediaRenderer{display:block}.InlineMedia a:active,.InlineMedia a:focus,.InlineMedia a:hover,.Theme-LinkedMediaRenderer:active,.Theme-LinkedMediaRenderer:focus,.Theme-LinkedMediaRenderer:hover,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:active,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:focus,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:hover{cursor:pointer;opacity:.9}.Theme-HeaderContainer{font-size:18px}.Theme-HeaderContainer,.Theme-Story{font-family:"PT Serif",serif;color:#333;-webkit-font-smoothing:antialiased;-moz-osx-font-smoothing:grayscale}.Theme-HeaderContainer ::-moz-selection{color:inherit;background-color:rgba(160,160,160,.55)}.Theme-Story ::-moz-selection{background-color:rgba(160,160,160,.55)}.Theme-HeaderContainer ::selection{color:inherit}.Theme-HeaderContainer ::selection,.Theme-Story ::selection{background-color:rgba(160,160,160,.55)}@media (min-width:900px){.Theme-HeaderContainer,.Theme-Story{font-size:18px}}@media (min-width:1100px){.Theme-HeaderContainer,.Theme-Story{font-size:20px}}@media (max-width:1400px){.Layout{width:auto}}@media (max-width:620px){.Theme-Layer-BodyText{width:100%}}.Theme-Layer-BodyText p,.Theme-Story p{display:block;margin-top:1.5rem;margin-bottom:1.5rem;line-height:1.7;font-family:"PT Serif",serif;font-weight:400;font-size:inherit}.Theme-OverlayedCaption a,.Theme-Section-Dark .Theme-Caption a,.Theme-Section-Dark .Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a,.Theme-Section[class*=Theme-ForegroundColor] a:not(.Theme-Layer-BodyText-Button){text-decoration:none;border-bottom:1px dotted}.Theme-Caption a,.Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a{text-decoration:none;border-bottom:1px dotted;color:#00a7cf}.Theme-OverlayedCaption a:hover,.Theme-Section[class*=Theme-ForegroundColor] a:hover:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:hover,.Theme-Layer-BodyText a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:hover{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:active,.Theme-Section[class*=Theme-ForegroundColor] a:active:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:active,.Theme-Layer-BodyText a:active:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:active{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:focus,.Theme-Section[class*=Theme-ForegroundColor] a:focus:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:focus,.Theme-Layer-BodyText a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:focus{color:#007e9c;border-bottom-style:solid}.Theme-Caption a:visited,.Theme-Layer-BodyText a:visited:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited{color:#03ceff}.Theme-OverlayedCaption a:visited:hover,.Theme-Section[class*=Theme-ForegroundColor] a:visited:hover:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:hover,.Theme-Layer-BodyText a:visited:hover:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:hover{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:visited:active,.Theme-Section[class*=Theme-ForegroundColor] a:visited:active:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:active,.Theme-Layer-BodyText a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:active{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:visited:focus,.Theme-Section[class*=Theme-ForegroundColor] a:visited:focus:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:focus,.Theme-Layer-BodyText a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:focus{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a,.Theme-Section-Dark .Theme-Caption a,.Theme-Section-Dark .Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a{color:#00a7cf}.Theme-OverlayedCaption a:active,.Theme-OverlayedCaption a:focus,.Theme-OverlayedCaption a:hover,.Theme-Section-Dark .Theme-Caption a:active,.Theme-Section-Dark .Theme-Caption a:focus,.Theme-Section-Dark .Theme-Caption a:hover,.Theme-Section-Dark .Theme-Layer-BodyText a:active:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:hover{color:#03ceff}.Theme-OverlayedCaption a:visited,.Theme-Section-Dark .Theme-Caption a:visited,.Theme-Section-Dark .Theme-Layer-BodyText a:visited:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited{color:#007e9c}.Theme-OverlayedCaption a:visited:active,.Theme-OverlayedCaption a:visited:focus,.Theme-OverlayedCaption a:visited:hover,.Theme-Section-Dark .Theme-Caption a:visited:active,.Theme-Section-Dark .Theme-Caption a:visited:focus,.Theme-Section-Dark .Theme-Caption a:visited:hover,.Theme-Section-Dark .Theme-Layer-BodyText a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:visited:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:hover{color:#03ceff}.Theme-Section[class*=Theme-ForegroundColor] a:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit}.Theme-Section[class*=Theme-ForegroundColor] a:active:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:hover:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit;opacity:.8}.Theme-Section[class*=Theme-ForegroundColor] a:visited:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit}.GalleryRenderer--initializing:after,.Theme-Lazyload-Spinner{position:absolute;top:50%;left:50%;width:26px;height:26px;margin-left:-13px;margin-top:-13px;border-radius:50%;border:4px solid #fff;border-bottom-color:transparent;-webkit-animation:loading-spinner forwards 1s linear infinite;animation:loading-spinner forwards 1s linear infinite;background:rgba(0,0,0,.5);-webkit-box-shadow:0 0 0 4px rgba(0,0,0,.5);box-shadow:0 0 0 4px rgba(0,0,0,.5)}.Theme-Lazyload-Spinner{opacity:.25}.Theme-Story{display:block;background-color:#fff;font-size:17px}@media (min-width:620px){.Theme-Story{font-size:18px}}@media (min-width:900px){.Theme-Story{font-size:18px}}@media (min-width:1100px){.Theme-Story{font-size:20px}}@media (min-width:1400px){.Theme-Story{font-size:20px}}@media (min-width:1750px){.Theme-Story{font-size:22px}}@media (min-width:2000px){.Theme-Story{font-size:22px}}.Theme-Story ::-moz-selection{background-color:#00a7cf;color:#fff}.Theme-Story ::selection{background-color:#00a7cf;color:#fff}.Theme-Story p{width:100%;color:inherit}.Theme-Story sub,.Theme-Story sup{font-size:70%;display:inline-block;line-height:1.7}.Theme-Story sub+a,.Theme-Story sup+a{margin-left:.25em}.Theme-Story sup{top:-.5em}.Theme-Story sub{bottom:-.25em}.Theme-Layer-BodyText-Heading-Large,.Theme-Layer-BodyText-Heading-Small,.Theme-Layer-BodyText-Heading-xs{display:block;width:100%}.Theme-Layer-BodyText-Heading-Large{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:150%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-Large{font-size:160%}}.Theme-Layer-BodyText-Heading-Small{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:130%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-Small{font-size:140%}}.Theme-Layer-BodyText-Heading-xs{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:inherit;font-weight:400;font-size:120%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-xs{font-size:130%}}.Theme-Layer-BodyText-List-Alpha,.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Roman,.Theme-Layer-BodyText-List-Unordered{padding-left:1.2rem;list-style-position:outside;font-size:inherit;font-weight:400;color:#333;margin-top:1.5rem;margin-bottom:1.5rem}.Theme-Layer-BodyText-List-Alpha{list-style-type:lower-alpha}.Theme-Layer-BodyText-List-Roman{list-style-type:lower-roman}.Theme-Layer-BodyText-List-Unordered{list-style-type:square}.Theme-Layer-BodyText-ListItem{line-height:1.7;margin-bottom:.5rem;font-family:"PT Serif",serif}.Theme-Layer-BodyText-Blockquote{display:block;padding-top:1.5rem;padding-bottom:1.5rem;padding-right:1.5rem;border-top:2px solid rgba(204,204,204,.3);border-bottom:2px solid rgba(204,204,204,.3);margin-top:1.5rem;margin-bottom:1.5rem;color:#777;font-family:"PT Serif",serif;font-weight:400;font-style:italic;font-size:120%;line-height:1.4}@media (min-width:620px){.Theme-Layer-BodyText-Blockquote{font-size:130%}}.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{display:block;margin:1rem 0 .5rem;font-family:"Lato",sans-serif;color:#777;line-height:1.2;font-style:normal;font-weight:400;font-size:13.6px}@media (min-width:620px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:14.4px}}@media (min-width:900px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:14.4px}}@media (min-width:1100px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:16px}}@media (min-width:1400px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:16px}}@media (min-width:1750px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:17.6px}}@media (min-width:2000px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:17.6px}}div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{display:block;float:left;max-width:100%;font-family:inherit;font-size:5.7em;font-style:inherit;font-weight:inherit;line-height:.825;margin-right:.05em;margin-top:0;margin-bottom:0}@media (min-width:620px){div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{font-size:5.7em}}.Theme-Layer-BodyText-Breakout{border:1px solid #333;background:rgba(255,255,255,.2);padding:25px}@media (min-width:620px){.Theme-Layer-BodyText-Breakout{padding:30px}}@media (min-width:1100px){.Theme-Layer-BodyText-Breakout{padding:40px}}.Theme-Layer-BodyText-Indent{border-left:4px solid rgba(51,51,51,.1);padding-left:25px}@media (min-width:620px){.Theme-Layer-BodyText-Indent{padding-left:30px}}@media (min-width:1100px){.Theme-Layer-BodyText-Indent{padding-left:40px}}.Theme-Story .Theme-Layer-BodyText-Highlight{background-color:rgba(51,51,51,.2)}.Theme-Story .Theme-Layer-BodyText-Highlight:hover{background-color:rgba(51,51,51,.4)}.Theme-Story .Theme-Layer-BodyText-Highlight:focus{background-color:rgba(51,51,51,.4);outline:#333 auto 1px}.Theme-Story .Theme-Layer-BodyText-Highlight .Theme-Layer-BodyText-Highlight--Icon{background-color:#333}.Theme-Story .Theme-Footnote{font-family:"PT Serif",serif;font-size:80%;line-height:1.5;color:#222;background-color:rgba(255,255,255,.95);-webkit-box-shadow:0 3px 10px 6px rgba(0,0,0,.1),0 0 0 1px rgba(0,0,0,.1);box-shadow:0 3px 10px 6px rgba(0,0,0,.1),0 0 0 1px rgba(0,0,0,.1)}.Theme-Story .Theme-Footnote:after{border-color:rgba(255,255,255,.95) transparent transparent}.Theme-Story .Theme-Footnote:before{content:"";position:absolute;top:100%;height:20px;width:100%;z-index:-1;left:0}.Theme-Story .Theme-Footnote a{color:inherit}.Theme-Story .Theme-Footnote.Theme-Position-Top:after{border-color:transparent transparent rgba(255,255,255,.95)}.Theme-Overlay{z-index:1;opacity:0;-webkit-transform:translateZ(0);transform:translateZ(0)}.Theme-Overlay.FullSize{top:-2px;bottom:-2px;height:auto;left:-2px;right:-2px;width:auto}.Theme-Layer-TextBlock-Inner{pointer-events:auto;font-family:"Lato",sans-serif;padding-left:env(safe-area-inset-left);padding-right:env(safe-area-inset-right);font-size:100%;width:100%}@media (min-width:750px){.Theme-Layer-TextBlock-Inner{width:90%}}@media (orientation:landscape) and (max-width:900px){.Theme-Layer-TextBlock-Inner{width:60%}}@media (min-width:900px){.Theme-Layer-TextBlock-Inner{max-width:750px}}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner{max-width:850px}}@media (min-width:1400px){.Theme-Layer-TextBlock-Inner{max-width:1100px}}@media (min-width:1750px){.Theme-Layer-TextBlock-Inner{max-width:1250px}}@media (min-width:900px){.Theme-Section:not(.Theme-Section-Layout--Half) .Layout__flex--xleft .Theme-Layer-TextBlock-Inner,.Theme-Section:not(.Theme-Section-Layout--Half) .Layout__flex--xright .Theme-Layer-TextBlock-Inner{width:60%}}.Theme-Layer-TextBlock-Inner a{color:#333}.Theme-Layer-TextBlock-Inner a:active,.Theme-Layer-TextBlock-Inner a:focus,.Theme-Layer-TextBlock-Inner a:hover{color:#333}.Theme-Layer-TextBlock-Inner a:visited{color:#333}.Theme-Layer-TextBlock-Inner .Theme-Title{color:#333;font-weight:400}.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-Title{text-transform:none;display:block;margin:0;padding:0;line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{text-transform:none;display:block;color:#333;margin:0;padding:0;line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-Byline{text-transform:none;display:block;margin:0;padding:0}.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:40px;padding-right:40px}}.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle{color:#333;font-family:"Lato",sans-serif;font-weight:400}.Theme-Layer-TextBlock-Inner .Theme-Byline{color:#777;line-height:1.1;font-size:.9em}.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{margin-top:.5rem}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{margin-top:1rem}}.Theme-Layer-TextBlock-Inner .Theme-LeadIn:first-child,.Theme-Layer-TextBlock-Inner .Theme-SubTitle:first-child,.Theme-Layer-TextBlock-Inner .Theme-Text:first-child{margin-top:0}.Theme-Layer-TextBlock-Inner .Theme-Title{font-family:"Lato",sans-serif}.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{font-family:inherit;font-weight:400}.InlineElement--Divider__container{display:-webkit-box;display:-ms-flexbox;display:flex;text-align:center;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center}.Theme-Layer-BodyText-Divider{display:inline-block;border:none;background-color:rgba(204,204,204,.75);height:2px;margin:2.1rem 0;overflow:hidden;width:50%}.Theme-Layer-BodyText-Button{display:inline-block;border:none;color:#fff;font-family:"Lato",sans-serif;font-weight:700;line-height:1.1;background:#00a7cf;font-size:90%;text-transform:initial;padding:.7em 1.4em;border-radius:.35em;cursor:pointer;margin-top:1.5rem;margin-bottom:1.5rem;text-decoration:none}.body-editor .Theme-Layer-BodyText-Button{color:#fff!important}.Theme-Layer-BodyText-Button:active,.Theme-Layer-BodyText-Button:focus,.Theme-Layer-BodyText-Button:hover{opacity:.9;text-decoration:none}.InlineMedia{text-align:center}.InlineMedia img{width:auto;height:auto;max-width:100%;margin:0 auto;display:inline-block}.InlineMedia.media-size-110 img{width:calc(100% + 50px)!important;max-width:calc(100% + 50px)!important;-webkit-transform:translate(-25px);transform:translate(-25px)}@media (min-width:620px){.InlineMedia.media-size-110 img{width:calc(100% + 60px)!important;max-width:calc(100% + 60px)!important;-webkit-transform:translate(-30px);transform:translate(-30px)}}@media (min-width:1100px){.InlineMedia.media-size-110 img{width:calc(100% + 80px)!important;max-width:calc(100% + 80px)!important;-webkit-transform:translate(-40px);transform:translate(-40px)}}.InlineMedia.media-size-100 img{width:100%!important;max-width:100%!important}.InlineMedia.media-size-90 img{width:90%!important;max-width:90%!important}.InlineMedia.media-size-80 img{width:80%!important;max-width:80%!important}.InlineMedia.media-size-70 img{width:70%!important;max-width:70%!important}.InlineMedia.media-size-60 img{width:60%!important;max-width:60%!important}.InlineMedia.media-size-50 img{width:50%!important;max-width:50%!important}.InlineMedia.media-size-40 img{width:40%!important;max-width:40%!important}.InlineMedia.media-size-30 img{width:30%!important;max-width:30%!important}.InlineMedia.media-size-20 img{width:20%!important;max-width:20%!important}.InlineMedia.media-size-10 img{width:10%!important;max-width:10%!important}.InlineMedia--image>a,.InlineMedia--image__inner>div a{border:none!important}.InlineMedia--image__inner{display:inline-block;font-size:0;max-width:100%}.InlineMedia--video video{width:100%}.Theme-Layer-BodyText{font-family:"PT Serif",serif;padding-top:calc(48px - 1.5rem);padding-bottom:48px;padding-left:25px;padding-right:25px}@media (max-width:619px){.Theme-Layer-BodyText{overflow:hidden}}@media (min-width:620px){.Theme-Layer-BodyText{padding-top:calc(60px - 1.5rem);padding-bottom:60px;padding-left:30px;padding-right:30px}}@media (min-width:900px){.Theme-Layer-BodyText{padding-top:calc(72px - 1.5rem)}}@media (min-width:1100px){.Theme-Layer-BodyText{padding-left:40px;padding-right:40px}}.Theme-Layer-BodyText .Theme-Overlay{position:absolute;top:0;left:0;right:0;bottom:0;z-index:-1}.Theme-Layer-BodyText p,.Theme-Layer-BodyText-Blockquote,.Theme-Layer-BodyText-Heading-Large,.Theme-Layer-BodyText-Heading-Small,.Theme-Layer-BodyText-Heading-xs,.Theme-Layer-BodyText-List-Alpha,.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Roman,.Theme-Layer-BodyText-List-Unordered,.Theme-Layer-BodyText-QuoteCite{margin-left:auto;margin-right:auto;text-transform:initial}.Theme-ButtonSize-xsmall .Theme-Layer-BodyText-Button{font-size:70%}.Theme-ButtonSize-small .Theme-Layer-BodyText-Button{font-size:80%}.Theme-ButtonSize-medium .Theme-Layer-BodyText-Button{font-size:90%}.Theme-ButtonSize-large .Theme-Layer-BodyText-Button{font-size:100%}.Theme-ButtonSize-xlarge .Theme-Layer-BodyText-Button{font-size:110%}.Theme-DividerSize-xlarge{width:100%}.Theme-DividerSize-xlarge+.InlineElement--UI__container .BlockBar-Align{display:none}.Theme-DividerSize-large{width:75%}.Theme-DividerSize-medium{width:50%}.Theme-DividerSize-small{width:25%}.Theme-DividerSize-xsmall{width:10%}.Theme-Layer-BodyText-Spacer,.Theme-SpacerSize-10{height:40px}.Theme-SpacerSize-20{height:80px;height:8vh}.Theme-SpacerSize-30{height:120px;height:16vh}.Theme-SpacerSize-40{height:180px;height:24vh}.Theme-SpacerSize-50{height:220px;height:32vh}.Theme-SpacerSize-60{height:280px;height:40vh}.Theme-SpacerSize-70{height:320px;height:50vh}.Theme-SpacerSize-80{height:360px;height:65vh}.Theme-SpacerSize-90{height:400px;height:85vh}.Theme-SpacerSize-100{height:440px;height:100vh}.Theme-Caption .caption-editor-empty{font-family:"Lato",sans-serif;font-size:.8em;font-weight:400;line-height:1.2;margin:0}.Theme-Caption cite,.Theme-Caption p:not(:empty){margin:0;max-width:100%}.Theme-Caption p:not(:empty){color:#777;font-weight:400;font-family:"Lato",sans-serif;font-style:normal;line-height:1.2;font-size:.8em;padding:.5em}.Theme-Caption [contenteditable=false],.Theme-Caption cite{padding:.5em}.Theme-Caption a{display:inline}.Theme-OverlayedCaption{background-color:rgba(34,34,34,.65);z-index:2}.Theme-CollectionSectionSection .Theme-OverlayedCaption,.Theme-TextOverMediaSection .Theme-OverlayedCaption,.Theme-TitleSection .Theme-OverlayedCaption{position:absolute;bottom:0;left:0;right:0}.Theme-OverlayedCaption p:not(:empty){color:rgba(255,255,255,.7);font-family:"Lato",sans-serif;font-size:.8em;line-height:1.2;margin:0;padding:.5em 25px}.Theme-OverlayedCaption [contenteditable=false]{padding:.5em 25px}.DisplayContainerHeight--heightThird .Theme-OverlayedCaption [contenteditable=false],.DisplayContainerHeight--heightThird .Theme-OverlayedCaption p:not(:empty){font-size:12px}@media (min-width:620px){.Theme-OverlayedCaption [contenteditable=false],.Theme-OverlayedCaption p:not(:empty){padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-OverlayedCaption [contenteditable=false],.Theme-OverlayedCaption p:not(:empty){padding-left:40px;padding-right:40px}}.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:40px;padding-right:40px}}.Theme-ImageCaption,.Theme-InlineMediaCaption p{text-align:center}.h-align-right .Theme-InlineMediaCaption p{text-align:right;padding-right:0}.h-align-left .Theme-InlineMediaCaption p{text-align:left;padding-left:0}.Theme-ImageCaption p:not(:empty),.Theme-InlineMediaCaption p:not(:empty){color:#777}.Theme-HeaderContainer{height:40px;background:#fff;-webkit-box-shadow:0 2px 2px -2px rgba(0,0,0,.3);box-shadow:0 2px 2px -2px rgba(0,0,0,.3)}@media (min-width:900px){.Theme-HeaderContainer{height:50px}}@media (min-width:1100px){.Theme-HeaderContainer{height:60px}}.Theme-HeaderContainer.Theme-Section-Custom{-webkit-box-shadow:none;box-shadow:none}.Theme-HeaderContainer .Theme-Header{width:100%;max-width:100%;padding-left:env(safe-area-inset-left);padding-right:env(safe-area-inset-right)}.Theme-Logos{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex;height:32px;margin-left:15px}@media (min-width:900px){.Theme-Logos{height:38px}}@media (min-width:1100px){.Theme-Logos{height:44px}}.Theme-Logo{display:inline-block;vertical-align:top;width:100%;min-width:auto;height:100%;margin-right:calc(10px + .5vw)}.body-editor .Theme-Logo{display:-webkit-box;display:-ms-flexbox;display:flex}.Theme-Logo a{display:block;height:100%}.Theme-Logo img{max-height:100%;max-width:none;width:auto;-ms-flex-negative:0;flex-shrink:0}.Theme-Default-Logos,.Theme-SocialIcons{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex}.Theme-Default-Logos,.Theme-Logo img{vertical-align:top;height:100%}.DeviceDetect--isIE .Theme-Default-Logos .Theme-Logo{min-width:100%}.Theme-SocialIcons{position:absolute;min-width:80px;height:32px;top:50%;margin-top:-16px;-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end;text-align:right;right:0;margin-right:15px}@media (min-width:1100px){.Theme-SocialIcons{position:absolute}}@media (max-width:1099px){.Theme-Hamburger~.Theme-SocialIcons{right:45px;right:calc(45px + env(safe-area-inset-right))}}.Theme-SocialButton{display:inline-block;vertical-align:top;margin-left:4px}.Theme-SocialButton a{display:block;border-radius:4px;overflow:hidden;width:32px;height:32px}.Theme-SocialButton a:after{content:"";display:block;position:absolute;top:0;left:0;right:0;bottom:0}.Theme-NavigationBar.Theme-NavigationBar-Sticky:before,.Theme-NavigationBar.Theme-Section-Custom:before,.Theme-NavigationBar.Theme-Section-Dark:before,.Theme-SocialButton img{display:none}.Theme-TwitterButton{background:#00aced}.Theme-TwitterButton:after{background:url(data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAFEAAADCCAMAAAAGo97pAAAAwFBMVEX////////7+/v////19fX////v7+/////////o6Oj////e3t7////W1tb////MzMz////ExMT///+6urr///+xsbH///+qqqr///+goKD///+SkpL///////+EhIT///95eXn///9ubm7///////9lZWX///9aWlr///9SUlL///9HR0f///8/Pz////83Nzf///8vLy////8pKSn///////8hISH///8YGBj///8NDQ3///8GBgb///8AAAD///9ooZKCAAAAPnRSTlMAAQQECgoQEBQXGiEhKSkzMzs7RUVOT1VeX2dtcXh7foaHkZGZmqOlq62wuLjAwMjI0NDW1t3e5eft8vP4+LQbORoAAAR2SURBVHgB7NTRirM6FMXxRQhCCFJEpIggpRCkFBERRIKs93+s02Gm/WrHmtTM3cnvWv64ZW+xJYqk0lorJfE3MjPxx3hKsSCTHb2OC43GgyjHR1Gm8CINX80VviXVSIO7elLwoHquaAQgj40lZ40fYmKfwEmNXHU9tTO/nHBXkOwkHGTPbb3EneFNm2Cb4bZJ42Hgl05hS+YKpgBUJXEj+W1MsaHjpl5DldfZ4IviD1vgrZybxlMz/vuUKR9OAm809HBfQs1/uhSrhKWbTfEt4ZO5FlhxoNt0wJ3lsyHHb6VHMMVDy6U2w6uaLp3afLzNsXSiQyPwRPO3sVIfFUssXLnmWmn/qUvPCxtMmQrcHP2L7v2dh8u5/nRqqImBCrw4zAyTLWoFgDwwqfEk51CnyCaGEL9u1nYtA4x4ljDcFQsDg52wcGawIxYODKaw1DHQgBc5A53x6sIwOfC3d20FfjlYBjBYkYUkM6xJR+41YJ08c6cK76Rm5g5WYpXEjaynkJteKu3Yj5afswrrpOU+Nd6pucsk8Y4cuUeJ9/LwnzfC57Yam0z4zKFv2cApn/iBQcJN1pa+Jg0vsrz6RecM3kRa9O5gjg/ozh0s4E/U9m+Dx4FOUwZfshzo1mv4Ebmx9NBIeFB5fbH0YUtsEaa9XK7tYOnrouBQfnZ4Bdxk5d0cKwEvshrooS8F/OWN5SZrMnxIHpuJb0ymkNglrUw3c8F251IjjEyU1umN1ioRiKIoiqIoiqIoiqIo+t/7r5s6UHFVh6IwvCSEioRQRERKSykVGUoREUUkyHr/t7od5tYeO9akpnDgfA/w69bs/OsCGSqlolDiM+Ki5//ak8aE3KzoVZz4UhiJXTsWpYYTmfPZsMePzb5lgbtDF8FBWHPGlwBk+mXIQY2v27PeOARbzrqeyoHfTrhLSVYSFrLmslriruBNucGynMs6hVHDb1WIJTGX9RpAuJe4kfzRaiyoLCMrRLvrkONbND4mxUsJF7Wnr/bxKTVHJ4EXCjq4H0LFh0pjluhpZzR+hJMdOAjM2NKu3+Ju+vwmwW8ZrTqNUcmpMsazI22qCA8HPiuTABMnWhQCD1D8rd1HbxUzTFw557p7RA/ORcuGNXmmBW5S96L9/A7N5Xx8d2qEHT2leLId6Cee1NIASDyTanqtNEcdxB19iF87a6qSHlr8aUN/V0w09HbCxJneUkxs6S3CVEVPDZ4k9HTGswv9JMBn97oX+GVr6CHHjNgnGWOObrlWE2CWPHOlPV7R+cAVjMQsiRt56Lx3epSZtm4N32dCzJM91znilSNX6SRekR3XyPBa8oHL239uo7Ao95/Z9y0LWCUd39BI2MmjoatewYnMrm7RIYYzodPaHkzwBlXZgynciYP5aDDIGlr1MVzJXUO7WsGNSHJDB4WEgzA5XAxdmAxLRF5eLteyMXR1iaw/4r3FS2En987Nbic++YNZZwLOgqQwXGTyGG+SadHxhS5PJVbRu7waOGHKc6bgJZCbSCl9o1S0Efjr/gMShvXLBlyyFgAAAABJRU5ErkJggg==) center no-repeat;background-size:18px auto;background-position-y:-20px}.Theme-FaceboookButton{background-color:#3b5998}.Theme-FaceboookButton:after{background:url(data:image/png;base64,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) center no-repeat;background-size:8px auto;background-position-y:-19px}.Theme-Hamburger{right:15px;right:calc(15px + env(safe-area-inset-right))}.Theme-Hamburger span{background:#333;height:3px}.Theme-NavigationBar{top:40px;background-color:rgba(34,34,34,.9);color:rgba(255,255,255,.6);width:100%;max-width:none;overflow-y:auto;-webkit-backdrop-filter:blur(5px);backdrop-filter:blur(5px)}@media (max-width:619px){.Theme-NavigationBar{min-width:100%}}@media (min-width:620px) and (max-width:1099px){.Theme-NavigationBar{max-width:400px}}@media (max-width:1099px){.Theme-NavigationBar{padding-bottom:40px}}@media (min-width:900px){.Theme-NavigationBar{top:50px}}@media (min-width:1100px){.Theme-NavigationBar{top:100%;position:absolute;left:0;right:0;padding:0 15px;display:block;-webkit-backdrop-filter:none;backdrop-filter:none;overflow:hidden}}@media (max-width:1099px){#Navigation__hamburgerToggle:checked~.Theme-NavigationBar{right:-15px}}@media (max-width:619px){#Navigation__hamburgerToggle:checked~.Theme-NavigationBar{left:-15px}}.Theme-NavigationBar.Theme-NavigationBar-Sticky,.Theme-NavigationBar.Theme-Section-Custom,.Theme-NavigationBar.Theme-Section-Dark{opacity:.95}.Theme-NavigationBar-Sticky{background:rgba(34,34,34,.9)}@media (min-width:1100px){.Theme-Navigation-ItemList{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;-ms-flex-wrap:wrap;flex-wrap:wrap}}.Theme-NavigationBarItem{padding:0;text-decoration:none;border-bottom:none;border-top:0 solid rgba(180,180,180,.4);color:inherit}.Theme-NavigationBarItem::after,.Theme-NavigationBarItem::before{display:none}@media (min-width:1100px){.Theme-NavigationBarItem{display:inline-block;border-top:none;margin:0}}.Theme-NavigationLink{font-family:"Lato",sans-serif;font-size:17px;font-weight:700;color:inherit;line-height:1;text-decoration:none;display:block;padding:15px;border:none}.Theme-NavigationLink:empty:before{content:"Untitled"}.Theme-ActiveNavigationBarItem .Theme-NavigationLink,.Theme-NavigationLink:active,.Theme-NavigationLink:hover{color:#fff;text-decoration:none}.Theme-NavigationLink:focus-within{color:#fff;text-decoration:none}@media (min-width:1100px){.Theme-NavigationLink{font-size:16px;padding:8px 10px;margin:0}}.Theme-Section-Custom .Theme-NavigationLink,.Theme-Section-Dark .Theme-NavigationLink{opacity:.6;color:inherit}.Theme-Section-Custom .Theme-NavigationLink:active,.Theme-Section-Custom .Theme-NavigationLink:hover,.Theme-Section-Dark .Theme-NavigationLink:active,.Theme-Section-Dark .Theme-NavigationLink:hover{color:inherit;opacity:1}.Theme-Section-Custom .Theme-NavigationLink:focus-within,.Theme-Section-Dark .Theme-NavigationLink:focus-within{color:inherit;opacity:1}.Theme-Section-Custom .Theme-ActiveNavigationBarItem .Theme-NavigationLink,.Theme-Section-Dark .Theme-ActiveNavigationBarItem .Theme-NavigationLink{color:inherit;opacity:1}@media (min-width:1100px){.Theme-SiteNavigationBar{overflow:visible}}.Theme-SiteNavigation-SubItemList{display:-webkit-box;display:-ms-flexbox;display:flex;padding:0;list-style:none}@media (max-width:1099px){.Theme-SiteNavigation-SubItemList{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column}}.Theme-MediaSection video,.Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink{width:100%}@media (min-width:1100px){.Theme-SiteNavigationBarSubItem:hover .Theme-SiteNavigation-ItemList--depth1 .Theme-SiteNavigation-SubItemList{height:auto;max-height:380px;min-width:200px;-webkit-transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;opacity:1;overflow-y:auto}.Theme-SiteNavigationBarSubItem:focus-within .Theme-SiteNavigation-ItemList--depth1 .Theme-SiteNavigation-SubItemList{height:auto;max-height:380px;min-width:200px;-webkit-transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;opacity:1;overflow-y:auto}.Theme-SiteNavigationBarSubItem>ul{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start}.Theme-SiteNavigationBarSubItem>ul>li{width:100%;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigation-ItemList{-ms-flex-wrap:nowrap;flex-wrap:nowrap}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:after{content:"";display:inline-block;width:0;height:0;border-style:solid;border-width:6px 4px 0;border-color:rgba(255,255,255,.6) transparent transparent;margin-left:5px}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:focus:after,.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:hover:after{border-color:#fff transparent transparent}}@media (max-width:1099px){.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink{padding-left:35px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink:not(:hover){background:rgba(255,255,255,.1)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink:before{content:"";display:inline-block;width:10px;height:1px;background-color:rgba(255,255,255,.6);margin-left:-18px;margin-right:8px}}@media (min-width:1100px){.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList{opacity:0;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;position:absolute;width:0;top:100%;left:0;max-height:0;overflow:hidden;border-top:0 solid transparent;-webkit-transition:opacity .15s ease-out .15s;transition:opacity .15s ease-out .15s;scrollbar-width:thin;border-top-right-radius:3px;border-top-left-radius:3px;border-bottom-right-radius:3px;border-bottom-left-radius:3px;-webkit-box-shadow:0 8px 5px -5px rgba(0,0,0,.2);box-shadow:0 8px 5px -5px rgba(0,0,0,.2)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar{width:9px;height:9px;background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-track{background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-thumb{background:rgba(255,255,255,.6);width:5px;height:5px;border-radius:10px;border:2px solid rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-thumb:hover{background:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink{color:rgba(255,255,255,.6);font-weight:700;padding:10px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:active,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:hover,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:active,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:hover{color:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:focus-within,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:focus-within{color:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li{background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:not(:last-child){border-bottom:1px solid rgba(255,255,255,.1)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:first-child{border-top:1px solid rgba(255,255,255,.1);border-top-right-radius:3px;border-top-left-radius:3px;padding-top:2px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:last-child{border-bottom-right-radius:3px;border-bottom-left-radius:3px;padding-bottom:5px}}@media (max-width:1099px){.Theme-SiteNavigationBarItem:hover{background:0 0;text-decoration:none}}.Theme-SiteNavigationLink{text-align:left}@media (max-width:1099px){.Theme-SiteNavigationLink{text-align:left;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigationLink:hover{text-decoration:underline;background:rgba(255,255,255,.2)}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden{height:0}@media (max-width:1099px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden{background:0 0;height:auto;width:auto;display:-webkit-box;display:-ms-flexbox;display:flex;right:0;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end;-webkit-box-shadow:none;box-shadow:none}}.body-editor .Theme-HeaderContainer.Theme-HeaderContainer--hidden{top:0}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Logos{display:none}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-SocialIcons{display:none!important}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Header{width:100%;max-width:100%;height:0}@media (max-width:1099px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Header{max-width:50px;height:auto;max-height:50px;margin:0;background-color:#fff;-webkit-box-shadow:0 2px 2px -2px rgba(0,0,0,.3);box-shadow:0 2px 2px -2px rgba(0,0,0,.3)}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Hamburger{margin:10px;position:relative;right:0;top:auto;-webkit-transform:none;transform:none}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar{top:0;border-top:50px solid #fff}}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar{position:absolute;top:100%;left:0;right:0;-webkit-transform:none;transform:none;margin:0}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar:not(.Theme-Section-Custom){background-color:rgba(34,34,34,.9)}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationLink{padding:8px 10px}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:100vh}.body-editor .Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 60px)}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-Layer-CardCanvas[data-card-canvas]{margin-top:50px;top:50px}}@media (max-width:899px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-Layer-CardCanvas[data-card-canvas]{top:0}}@media (max-width:1099px){body:not(.body-editor) .Theme-HeaderContainer.Theme-HeaderContainer--hidden.Theme-HeaderContainer--navigable+.Theme-Story{margin-top:-50px}}.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{margin:0;padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{padding-left:40px;padding-right:40px}}.Theme-TextOverMediaSection .InlineMedia img,.Theme-TitleSection .InlineMedia img{margin:5px auto;opacity:1}.Theme-TextOverMediaSection .InlineMedia--video,.Theme-TextOverMediaSection .InlineMedia--youTube,.Theme-TextOverMediaSection .InlineMedia-Soundcloud,.Theme-TextOverMediaSection .RichEmbed--soundcloud,.Theme-TextOverMediaSection .RichEmbed--youtube,.Theme-TitleSection .InlineMedia--video,.Theme-TitleSection .InlineMedia--youTube,.Theme-TitleSection .InlineMedia-Soundcloud,.Theme-TitleSection .RichEmbed--soundcloud,.Theme-TitleSection .RichEmbed--youtube{margin:.5rem 0}.DisplayContainerHeight--flex,.DisplayContainerHeight--flex .Layer--one{display:-webkit-box;display:-ms-flexbox;display:flex}.DisplayContainerHeight--flex .Layer--one{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-flex:1;-ms-flex:1;flex:1;width:100%;padding:calc(4vh + 40px) 0}.CardCanvas--tworowContainer .CardCanvasItem__image img,.DisplayContainerHeight--flex .DisplayContainerHeight{height:100%}.DisplayContainerHeight--minHeightHalf .Layer--one{padding:calc(2vh + 30px) 0}.DisplayContainerHeight--minHeightThird .Layer--one{padding:calc(2vh + 20px) 0}.DisplayContainerHeight--flex:not(.SplitLayout){-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column}.Theme-Layer-TextBlock-Container{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-flex:1;-ms-flex:1;flex:1;height:100%}.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 40px)}@media (min-width:900px){.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 50px)}}@media (min-width:1100px){.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 60px)}}.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 100px)}@media (min-width:900px){.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 110px)}}@media (min-width:1100px){.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 120px)}}@media (orientation:portrait){.DeviceDetect--isiPhone .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .Theme-TitleSection.DisplayContainerHeight--minHeight .Layer--one{padding-bottom:80px}}@media (orientation:portrait) and (min-device-height:700px){.DeviceDetect--isiPhone .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .Theme-TitleSection.DisplayContainerHeight--minHeight .Layer--one{padding-bottom:120px}}.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container{-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start;-webkit-box-flex:0;-ms-flex:0 0 auto;flex:0 0 auto;height:auto}.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container .Theme-Layer-TextBlock-Inner>div:not(:empty){padding-top:20px}@media (orientation:landscape){.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container .Theme-Layer-TextBlock-Inner>div:not(:empty){min-height:80px}}@media (max-width:899px){.Theme-TextSection.Theme-Columns--2 .Theme-Column:first-child .Theme-Layer-BodyText{padding-bottom:0}.Theme-TextSection.Theme-Columns--2 .Theme-Column:last-child .Theme-Layer-BodyText{padding-top:0}.Theme-TextSection.Theme-Columns--2 .Theme-Column:last-child .Theme-Layer-BodyText--inner p:first-child{margin-top:0}}@media (max-width:619px){.Theme-TextSection.Theme-Columns--2 .Theme-Column{min-width:100%}}.Theme-BackgroundScrollmationSection{background-color:#222}@media (max-width:900px){.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{margin-top:70vh;margin-bottom:70vh}}@media (min-width:1100px){.Theme-TwoColumnScrollmationSection .Theme-Layer-BodyText{padding-top:calc(72px - 1.5rem)}}.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:40px 25px}@media (min-width:620px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:60px 25px}}@media (min-width:900px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:72px 40px 60px}}@media (min-width:1100px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding-top:110px}}.Theme-TwoColumnScrollmationCaption{padding-top:40px}@media (min-width:620px){.Theme-TwoColumnScrollmationCaption{padding-top:60px}}@media (min-width:900px){.Theme-TwoColumnScrollmationCaption{padding-top:72px}}@media (min-width:1100px){.Theme-TwoColumnScrollmationCaption{padding-top:110px}}.Theme-LinkedMediaRenderer{-webkit-transition:opacity .15s ease;transition:opacity .15s ease}.Theme-Layer-CardCanvas[data-card-canvas]{padding-top:0;padding-bottom:0;margin-top:78px;top:78px}@media (max-width:899px){.Theme-Layer-CardCanvas[data-card-canvas]{height:35vh!important;top:40px}}@media (min-width:1100px){.Theme-Layer-CardCanvas[data-card-canvas]{margin-top:76.8px;top:106.8px}}.DeviceDetect--isEdge .Theme-Layer-CardCanvas[class*=StickyPolyfillElement],.DeviceDetect--isIE .Theme-Layer-CardCanvas[class*=StickyPolyfillElement]{margin-top:0}@media (max-width:899px){.CardCanvas--tworowContainer .CardCanvas{padding:0;margin:0;-webkit-box-shadow:0 1px 1px rgba(0,0,0,.1);box-shadow:0 1px 1px rgba(0,0,0,.1);-webkit-backdrop-filter:blur(3px);backdrop-filter:blur(3px)}.Theme-Section-Light .CardCanvas--tworowContainer .CardCanvas{background-color:rgba(255,255,255,.9)}.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:calc(35vh + 10px)}}@media (max-width:899px) and (max-aspect-ratio:6/8){.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:calc(35vh + 10px)}}@media (max-width:899px){.CardCanvas--tworowContainer .CardCanvas__canvasColumn{pointer-events:none}.CardCanvas--tworowContainer .CardCanvas__canvasColumn .Theme-Caption{pointer-events:auto}.CardCanvas--tworowContainer .CardCanvasItem__caption{right:4px;bottom:4px;left:4px;max-width:initial}.CardCanvas--tworowContainer .CardCanvasItem{padding:4px;pointer-events:initial}}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:15px}@media (min-width:620px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:25px}}@media (min-width:900px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:30px}}@media (min-width:1100px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:40px}}.Theme-Layer-Gallery-List a,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image .Theme-Item-Picture{display:block}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image img{max-width:100%;height:auto}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a{border:none}.Theme-Layer-ResponsiveMedia-embed .RichEmbed--facebook,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--instagram,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--linkedin,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--pinterest,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--twitter,.Theme-Layer-responsive-media-embed .RichEmbed--facebook,.Theme-Layer-responsive-media-embed .RichEmbed--instagram,.Theme-Layer-responsive-media-embed .RichEmbed--linkedin,.Theme-Layer-responsive-media-embed .RichEmbed--pinterest,.Theme-Layer-responsive-media-embed .RichEmbed--twitter{padding:15px 0}.Theme-Layer-ResponsiveMedia-embed .twitter-tweet,.Theme-Layer-responsive-media-embed .twitter-tweet{margin:0 auto!important}.Theme-RevealSection .Theme-Layer-BodyText{width:95%;border-radius:.5em;padding-top:10px;padding-bottom:10px;margin:0 auto}@media (min-width:620px){.Theme-RevealSection .Theme-Layer-BodyText{padding-top:10px;padding-bottom:10px}}@media (min-width:1100px){.Theme-RevealSection .Theme-Layer-BodyText{padding-top:20px;padding-bottom:20px}}.Theme-RevealSection .Theme-Layer-BodyText .Theme-Overlay{border-radius:.5em}.MediaGallery{z-index:91}body:not(.body-editor) .MediaGallery{padding:15px}.body-editor .MediaGallery{margin:15px}@media (min-width:620px){body:not(.body-editor) .MediaGallery{padding:25px}.body-editor .MediaGallery{margin:25px}}@media (min-width:900px){body:not(.body-editor) .MediaGallery{padding:30px}.body-editor .MediaGallery{margin:30px}}@media (min-width:1100px){body:not(.body-editor) .MediaGallery{padding:40px}.body-editor .MediaGallery{margin:40px}.MediaGallery--Wide{margin-left:0;margin-right:0}.MediaGallery--Wide .Layout{padding-left:40px;padding-right:40px}}.MediaGallery__cell{margin:2px}@media (min-width:620px){.MediaGallery--Full .MediaGallery__cell,.MediaGallery--Narrow .MediaGallery__cell,.MediaGallery--Wide .MediaGallery__cell{margin:4px}}.MediaGallery__cell:first-child{margin-left:0}.MediaGallery__cell:last-child{margin-right:0}body:not(.body-editor) .MediaGallery__cell .Theme-BackgroundMedia{overflow:hidden}.MediaGallery__cell .Theme-Overlay{display:none}.MediaGallery--lightbox{background:rgba(34,34,34,.95)}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Lazyload{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;height:100%}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Lazyload{position:relative;overflow:hidden;margin:0 auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .FullSize{position:relative}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia img{width:auto;height:auto;max-width:100%;max-height:70vh}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia video{height:100%;margin:0 auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Videoplayer{overflow:hidden;width:auto;max-width:100%;height:100%;max-height:70vh}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Theme-Video-Wrapper,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Theme-Video-Wrapper>div,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr__video-wrapper{height:100%}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr__video-wrapper{width:auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia>a{position:relative;border:1px solid #fff}.MediaGallery--lightbox .Theme-BackgroundVideo .Theme-Item-Picture{display:none}.MediaGallery--lightbox .Theme-Caption{margin-top:.25em;overflow:auto;max-width:100%;text-align:center;opacity:.6}.MediaGallery--lightbox .Theme-Caption p{color:#fff;font-size:.9em;line-height:1.3}.MediaGallery--lightbox__controls span{background-color:#fff}.Theme-MediaGallerySection.Theme-Section-Light+.Theme-MediaSection.Theme-Section-Light .Theme-Layer-ResponsiveMedia-image{padding-top:0}.Theme-MediaGallerySection.Theme-Section-Light+.Theme-MediaGallerySection.Theme-Section-Light .MediaGallery{margin-top:0}.Theme-MediaGallerySection.Theme-Section-Dark+.Theme-MediaSection.Theme-Section-Dark .Theme-Layer-ResponsiveMedia-image{padding-top:0}.Theme-MediaGallerySection.Theme-Section-Dark+.Theme-MediaGallerySection.Theme-Section-Dark .MediaGallery{margin-top:0}.GalleryRenderer--initializing{min-height:30vh}.GalleryRenderer--initializing:after{content:"";opacity:.15}.Theme-CollectionSectionSection,.Theme-SitePagesSection{overflow:hidden;min-height:auto}.body-editor:not(.body-focus-mode) .Theme-CollectionSectionSection,.body-editor:not(.body-focus-mode) .Theme-SitePagesSection{min-height:auto}.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:25px;padding-bottom:calc(25px + 45px)}@media (min-width:620px){.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:30px;padding-bottom:calc(30px + 45px)}}@media (min-width:900px){.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:40px;padding-bottom:calc(40px + 45px)}}.body-editor .Theme-CollectionSectionSection,.body-editor .Theme-SitePagesSection{min-height:300px}.Theme-Layer-Gallery-Heading{color:#333;margin-top:0;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:150%;line-height:1.3;text-align:center}@media (min-width:620px){.Theme-Layer-Gallery-Heading{font-size:160%}}.Theme-Layer-Gallery-Heading:empty{display:none}.Theme-Layer-Gallery-List{margin:0 auto;padding:0;list-style:none;display:-webkit-box;display:-ms-flexbox;display:flex;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;justify-items:center;-webkit-box-align:stretch;-ms-flex-align:stretch;align-items:stretch}.Theme-Layer-Gallery-List a:active,.Theme-Layer-Gallery-List a:focus,.Theme-Layer-Gallery-List a:hover{text-decoration:none}.Theme-Layer-Gallery-List img{display:block;width:100%;margin:0 auto}.Theme-Layer-Gallery-Item{background-color:rgba(255,255,255,.6);border:1px solid rgba(34,34,34,.2);-webkit-transition:border .15s ease;transition:border .15s ease;margin:10px;text-align:center;width:100%;max-width:400px;min-width:240px}@media (min-width:620px){.Theme-Layer-Gallery-Item{margin:15px}}.Theme-Layer-Gallery-Item:only-of-type{width:100%;max-width:800px}.Theme-Layer-Gallery-Item:active,.Theme-Layer-Gallery-Item:focus,.Theme-Layer-Gallery-Item:hover{border:1px solid rgba(34,34,34,.5);background-color:rgba(255,255,255,.8);outline:none}.Theme-Layer-Gallery-Item:focus-within{border:1px solid rgba(34,34,34,.5);background-color:rgba(255,255,255,.8);outline:2px solid}.Theme-Layer-Gallery-Item a{border:none!important;text-decoration:none;height:100%;padding:10px}@media (min-width:620px){.Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{overflow:hidden}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}@media (min-width:620px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{color:#333;margin:15px 0 10px;font-family:"Lato",sans-serif;font-weight:700;font-size:110%;line-height:1.2}@media (min-width:900px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{font-size:110%}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description:empty,.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title:empty{margin:0}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{color:#333;margin-top:0;margin-bottom:10px;font-family:inherit;font-weight:400;font-size:90%;line-height:1.2}@media (min-width:900px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{font-size:90%}}.Theme-Collection--Default:not(:empty) .Layout{max-width:100%}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Layout{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-Collection--List:not(:empty) .Layout{padding-left:40px;padding-right:40px}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Heading{margin-bottom:.5em}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-List{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item{text-align:left;max-width:100%;width:100%;border-top:1px solid rgba(34,34,34,.2);border-bottom:1px solid rgba(34,34,34,.2);border-left:none;border-right:none;margin:0}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:not(:first-child){border-top:none}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active,.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus,.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover{background-color:rgba(255,255,255,.8);border-top:1px solid rgba(34,34,34,.2);border-bottom:1px solid rgba(34,34,34,.2)}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active:not(:first-child),.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus:not(:first-child),.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover:not(:first-child){border-top:none}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item a{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;padding:10px}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{overflow:hidden;margin-right:10px;max-width:30%}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{margin-right:25px;max-width:25%}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{-webkit-box-flex:1;-ms-flex:1;flex:1;padding:0}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{margin-top:0}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{margin-bottom:0}.Theme-Collection--Grid:not(:empty) .Layout{max-width:100%}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item{background-color:transparent;border:none;width:100%;text-align:center;margin:0}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item{margin:0}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:focus .Theme-Layer-Gallery-Item-Media,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:hover .Theme-Layer-Gallery-Item-Media{opacity:.3}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:focus img,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:hover img{-webkit-transform:scale(1.05);transform:scale(1.05)}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item a{background-color:#222;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;padding:10px}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{margin:6vh auto;padding:0}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{color:#fff}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{margin-top:0}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{margin-bottom:0}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{position:absolute;top:0;left:0;right:0;bottom:0;opacity:.4;overflow:hidden;-webkit-transition:opacity .15s ease-in-out;transition:opacity .15s ease-in-out}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item img{-o-object-fit:cover;object-fit:cover;height:100%;-webkit-transition:-webkit-transform .15s ease-in-out;transition:transform .15s ease-in-out;transition:transform .15s ease-in-out,-webkit-transform .15s ease-in-out}.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{width:50%}}@media (min-width:900px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{width:25%;min-width:25%}}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item-Text{margin:7.5vh auto}}.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item{border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item{width:50%;max-width:50%}.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item-Text{margin:10vh auto}}.Theme-Collection--Grid:not(:empty).Theme-Collection--Large .Theme-Layer-Gallery-Item{max-width:100%;border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Large .Theme-Layer-Gallery-Item-Text{margin:12vh auto}}.Theme-Layer-SiteGallery-Item.Theme-Layer-Gallery-Item--active,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left:before,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right:before{display:none}.Theme-Footer{z-index:100;height:60px;background:#fff;border-top:1px solid rgba(0,0,0,.1);padding:10px 15px}.Theme-Footer>.Layout{-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:-webkit-box;display:-ms-flexbox;display:flex}.Theme-Footer a,.Theme-Footer a:active,.Theme-Footer a:focus,.Theme-Footer a:hover,.Theme-Footer a:visited,.Theme-Footer a:visited:active,.Theme-Footer a:visited:focus,.Theme-Footer a:visited:hover{border-bottom:none}.Theme-Footer .Layout__snap--xright{padding:0}@media (max-width:620px){.Theme-Footer .Layout__snap--xright{width:auto;right:auto;left:0}}.Theme-Footer .Theme-FooterTopLink{width:60px;height:40px;font-size:11px;text-transform:uppercase;color:#333;text-decoration:none;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Oxygen-Sans,Ubuntu,Cantarell,"Helvetica Neue",sans-serif}@media (max-width:620px){.Theme-Footer .Theme-FooterTopLink{left:auto;top:auto;display:block;-webkit-transform:initial;transform:initial;right:0}}.Theme-Footer .Theme-FooterTopLink:before{border-style:solid;border-width:1px 1px 0 0;content:"";display:block;height:16px;left:50%;position:relative;top:8px;margin-bottom:4px;-webkit-transform:rotate(-45deg);transform:rotate(-45deg);width:16px;margin-left:-8px}.Theme-Footer .Theme-FooterTopLink:hover{color:#333;opacity:.65;text-decoration:none}.Theme-Footer .Theme-CreatedWithShorthand{display:block;height:40px;margin-top:-1px;width:auto;max-width:none}@media (min-width:620px){.Theme-Footer .Theme-CreatedWithShorthand{float:right}}.Theme-Footer .Theme-FooterLogo--container{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;font-size:14px;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Oxygen-Sans,Ubuntu,Cantarell,"Helvetica Neue",sans-serif;text-decoration:none;color:#222;-webkit-transition:opacity .15s ease-in-out;transition:opacity .15s ease-in-out}.Theme-Footer .Theme-FooterLogo--container:active,.Theme-Footer .Theme-FooterLogo--container:hover{opacity:.9}.Theme-Footer .Theme-FooterLogo{width:35px;margin-right:7px;font-size:0}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxsmall{font-size:calc(1em + 1vmin);line-height:1.2}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxsmall{font-size:calc(1em + 2vmin);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xsmall{font-size:calc(1em + 3.5vmin);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-small{font-size:calc(1em + 5vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-normal{font-size:calc(1em + 6.5vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-large{font-size:calc(1em + 8vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xlarge{font-size:calc(1em + 10vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxlarge{font-size:calc(1em + 12vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxlarge{font-size:calc(1em + 13vmin);line-height:1}@media (max-width:620px),(orientation:landscape) and (max-width:900px){.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxsmall{font-size:1em;line-height:1.4}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxsmall{font-size:calc(1em*1.25);line-height:1.3}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xsmall{font-size:calc(1em*1.5);line-height:1.2}.Theme-Layer-TextBlock-Inner .Theme-TextSize-small{font-size:calc(1em*1.75);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-normal{font-size:calc(1em*2);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-large{font-size:calc(1em*2.5);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xlarge{font-size:calc(1em*3);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxlarge{font-size:calc(1em*3.6);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxlarge{font-size:calc(1em*4.75);line-height:1}}@media (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{width:100%;margin:0}}@media (min-width:620px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:450px}}@media (min-width:900px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:525px}}@media (min-width:1100px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:620px}}@media (min-width:1400px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:680px}}@media (min-width:1750px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:780px}}@media (min-width:2000px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:880px}}.Theme-Section-Light,.Theme-Section-Light.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText,.Theme-Section-Light.Theme-BackgroundScrollmationSection .Theme-Overlay,.Theme-Section-Light.Theme-RevealSection .Theme-Overlay,.Theme-Section-Light.Theme-TextOverMediaSection .Theme-Overlay,.Theme-Section-Light.Theme-TitleSection .Theme-Overlay{background-color:#fff}.Theme-Section-Dark{background-color:#222;color:#fff}.Theme-Section-Dark.Theme-TextOverMediaSection .Theme-Overlay,.Theme-Section-Dark.Theme-TitleSection .Theme-Overlay{background-color:#000}.Theme-Section-Dark .Theme-Layer-BodyText p,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-Large,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-Small,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-xs,.Theme-Section-Dark .Theme-Layer-BodyText-List-Alpha,.Theme-Section-Dark .Theme-Layer-BodyText-List-Ordered,.Theme-Section-Dark .Theme-Layer-BodyText-List-Roman,.Theme-Section-Dark .Theme-Layer-BodyText-List-Unordered{color:#fff}.Theme-Section-Dark .Theme-Caption p,.Theme-Section-Dark .Theme-Layer-BodyText-Blockquote,.Theme-Section-Dark .Theme-Layer-BodyText-QuoteCite{color:rgba(255,255,255,.7)}.Theme-Section-Dark div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{color:inherit}.Theme-Section-Dark .Theme-Layer-BodyText-Breakout{background:rgba(34,34,34,.2);border-color:#fff}.Theme-Section-Dark .Theme-Layer-BodyText-Indent{border-left-color:rgba(255,255,255,.1)}.Theme-Section-Dark .Theme-Layer-BodyText-Button{color:#fff}.Theme-Section-Dark .Theme-Layer-BodyText-Button:not([class*=Theme-BackgroundColor]){background:#00a7cf}.body-editor .Theme-Section-Dark .Theme-Layer-BodyText-Button{color:#fff!important}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight{background-color:rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight:hover{background-color:rgba(255,255,255,.4)}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight:focus{background-color:rgba(255,255,255,.4);outline:#fff auto 1px}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight .Theme-Layer-BodyText-Highlight--Icon{background-color:#fff}.Theme-Section-Dark .Theme-Layer-TextBlock-Inner,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a{color:#fff}.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:hover{color:#fff}.Theme-Section-Dark .Theme-Layer-Gallery-Heading,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Title,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited{color:#fff}.Theme-Section-Dark .Theme-Layer-Gallery-Item{background-color:rgba(34,34,34,.6);border:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Layer-Gallery-Item:active,.Theme-Section-Dark .Theme-Layer-Gallery-Item:focus,.Theme-Section-Dark .Theme-Layer-Gallery-Item:hover{border:1px solid rgba(255,255,255,.5);background-color:rgba(34,34,34,.8)}.Theme-Section-Dark .Theme-Layer-Gallery-Item-Description,.Theme-Section-Dark .Theme-Layer-Gallery-Item-Title{color:#fff}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item{background-color:rgba(34,34,34,.6);border-top:1px solid rgba(255,255,255,.2);border-bottom:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:not(:first-child){border-top:none}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active,.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus,.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover{background-color:rgba(34,34,34,.8);border-top:1px solid rgba(255,255,255,.2);border-bottom:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark.Theme-RevealSection .Theme-Overlay{background-color:#222}@media (max-width:899px){.Theme-Section-Dark .CardCanvas--tworowContainer .CardCanvas{background-color:rgba(34,34,34,.9)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{background:rgba(0,0,0,.7)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Overlay{background-color:#000}}@media (min-width:900px){.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Center .Theme-Layer-BodyText{background:rgba(0,0,0,.7)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Center .Theme-Overlay{background-color:#000}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Layer-BodyText{height:100%}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left:before{content:"";display:block;width:70%;max-width:1500px;z-index:91;position:absolute;top:0;left:0;bottom:0;background:-webkit-gradient(linear,right top,left top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.65)),color-stop(60%,rgba(0,0,0,.8)));background:linear-gradient(270deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.65) 30%,rgba(0,0,0,.8) 60%)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Overlay{height:auto;right:auto;width:140%;left:0;background:-webkit-gradient(linear,right top,left top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.8)),color-stop(60%,#000));background:linear-gradient(270deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.8) 30%,#000 60%);-webkit-box-shadow:-700px 0 0 #000;box-shadow:-700px 0 0 #000}.body-editor .Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Overlay{top:-2px;bottom:-2px;-webkit-box-shadow:-440px 0 0 #000;box-shadow:-440px 0 0 #000}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Layer-BodyText{height:100%}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right:before{content:"";display:block;width:70%;max-width:1500px;z-index:91;position:absolute;top:0;right:0;left:auto;bottom:0;background:-webkit-gradient(linear,left top,right top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.65)),color-stop(60%,rgba(0,0,0,.8)));background:linear-gradient(90deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.65) 30%,rgba(0,0,0,.8) 60%)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Overlay{height:auto;left:auto;width:140%;right:0;background:-webkit-gradient(linear,left top,right top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.8)),color-stop(60%,#000));background:linear-gradient(90deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.8) 30%,#000 60%);-webkit-box-shadow:700px 0 0 #000;box-shadow:700px 0 0 #000}.body-editor .Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Overlay{top:-2px;bottom:-2px;-webkit-box-shadow:440px 0 0 #000;box-shadow:440px 0 0 #000}}.Theme-Section-Custom:not([class*=Theme-BackgroundColor]):not(.Theme-NavigationBar){background-color:#fff}.Theme-Section-HasOverlay .Theme-Layer-BodyText{background-color:transparent!important}.Theme-CustomHtmlSection,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{background-color:transparent}.Theme-Section[class*=Theme-ForegroundColor] .Theme-Caption p,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Blockquote,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Dropcap,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-Large,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-Small,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-xs,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Alpha,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Ordered,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Roman,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Unordered,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-QuoteCite,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Heading,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item a,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Title{color:inherit}.Theme-Section a span[class*=Theme-ForegroundColor],.Theme-Section a:visited span[class*=Theme-ForegroundColor]{border-bottom:1px dotted}.Theme-Section a:active span[class*=Theme-ForegroundColor],.Theme-Section a:focus span[class*=Theme-ForegroundColor],.Theme-Section a:hover span[class*=Theme-ForegroundColor],.Theme-Section a:visited:active span[class*=Theme-ForegroundColor],.Theme-Section a:visited:focus span[class*=Theme-ForegroundColor],.Theme-Section a:visited:hover span[class*=Theme-ForegroundColor]{border-bottom:1px solid}.h-align-left{text-align:left!important}.h-align-left.InlineElement{-webkit-box-pack:start;-ms-flex-pack:start;justify-content:flex-start}.h-align-center{text-align:center!important}.h-align-center.InlineElement{-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center}.h-align-right{text-align:right!important}.h-align-right.InlineElement{-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end}@media (min-width:900px){.Theme-BodyTextColumn-Left .Theme-Layer-BackgroundCanvas .Theme-Lazyload-Spinner{left:75%}.Theme-BodyTextColumn-Right .Theme-Layer-BackgroundCanvas .Theme-Lazyload-Spinner{left:25%}}@-webkit-keyframes loading-spinner{0%{-webkit-transform:rotate(0deg);transform:rotate(0deg)}to{-webkit-transform:rotate(360deg);transform:rotate(360deg)}}@keyframes loading-spinner{0%{-webkit-transform:rotate(0deg);transform:rotate(0deg)}to{-webkit-transform:rotate(360deg);transform:rotate(360deg)}}.custom-ad{text-align:center;padding:15px 0;background-color:rgba(0,0,0,.035)}.custom-ad div{margin:0 auto}.custom-ad .custom-ad-label{font-size:11px;text-transform:uppercase;color:rgba(80,80,80,.5);margin-bottom:5px;margin-top:-8px}hr{border:none;border-bottom:2px solid rgba(204,204,204,.3)}.Core--rootElement .oo-player-container *{position:initial}.sh-text-xs{font-size:12px}.sh-text-sm{font-size:14px}.sh-text-md{font-size:80%}.sh-text-lg{font-size:120%}.sh-text-xl{font-size:150%}[dir=rtl] .Theme-SocialIcons{right:auto;margin-right:0;left:0;margin-left:15px}@media (max-width:1099px){[dir=rtl] .Theme-Hamburger~.Theme-SocialIcons{left:45px;left:calc(45px + env(safe-area-inset-left))}}[dir=rtl] .Theme-Hamburger{right:auto;left:15px;left:calc(15px + env(safe-area-inset-left))}@media (max-width:1099px){[dir=rtl] .Theme-NavigationBar{right:auto!important;left:-110%!important;-webkit-transition:left .15s ease-in-out;transition:left .15s ease-in-out}[dir=rtl] .Navigation--isActive{right:auto!important;left:0!important}}.body-editor .MediaRenderer__textBlocksInner:first-child>div{padding-top:0;top:-20vh}.body-editor .Theme-Layer-BodyText--inner h2,.body-editor .Theme-Layer-BodyText--inner h3,.body-editor .Theme-Layer-BodyText--inner h4,.body-editor .Theme-Layer-BodyText--inner p{min-height:1.7em}.body-editor .RichEmbed--typeform{pointer-events:none}.body-editor .Theme-Layer-responsive-media-embed .Theme-Caption p{text-align:left}.InstantImage__img{-webkit-filter:blur(15px);filter:blur(15px)}.Theme-Layer-BodyText-Dropcap:after{content:"";clear:both;display:table}body{overflow:initial}.Theme-HeaderContainer b,.Theme-HeaderContainer strong,.Theme-Story b,.Theme-Story strong{font-weight:700}.Theme-HeaderContainer p:empty,.Theme-Story p:empty{padding:0;margin:0}.Theme-Layer-BodyText{word-wrap:break-word}.Layout,.Theme-Caption,.Theme-Column{padding-left:0;padding-right:0}@media (min-width:1100px) and (max-width:1399px){.Layout:not(.Theme-Header){max-width:1240px}}.Layout__row{margin:0}.Theme-Layer-TextBlock{pointer-events:none}.BlockHTML iframe,.InlineHTML iframe{border:none;max-width:100%}.BlockHTML .instagram-media,.InlineHTML .instagram-media{margin:0 auto!important}.InlineHTML img{max-width:100%;max-height:100%}.body-editor .Theme-HeaderContainer,.body-editor .Theme-Story{opacity:1}.DeviceDetect--isIE .FullSize--fixedChild{z-index:auto}.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:40px}@media (min-width:620px){.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:50px}}@media (min-width:900px){.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:60px}}.Theme-360Video-Link,.video_360_ios_link{overflow:hidden;display:block}.Theme-360Video-Button,.video-btn{position:absolute;display:inline-block;width:225px;top:50%;z-index:1;left:50%;background:rgba(0,0,0,.6) url(data:image/png;base64,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) 12px 12px no-repeat;background-size:20px auto;padding:12px 0 12px 38px;letter-spacing:0;border-radius:4px;text-transform:uppercase;font-weight:700;color:#fff;-webkit-transform:translate(-50%,-50%);transform:translate(-50%,-50%);text-align:left;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Helvetica,Arial,sans-serif,"Apple Color Emoji","Segoe UI Emoji","Segoe UI Symbol";font-size:14px;line-height:1;-webkit-box-shadow:0 0 0 1000px rgba(0,0,0,.1);box-shadow:0 0 0 1000px rgba(0,0,0,.1)}.twitter-tweet{margin:0 auto}@media (min-width:900px){.Theme-Layer-BodyText-List-Ordered+.Core--md-srOnly+.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Unordered+.Core--md-srOnly+.Theme-Layer-BodyText-List-Unordered{margin-top:-.75rem}html:not(.DeviceDetect--isEdge):not(.DeviceDetect--isIE) .CardCanvasItem__image img{max-width:750px;max-height:75vh!important}}.DeviceDetect--isIE .Theme-Layer-BodyText .InlineMedia--image .Lazyload__loading,.DeviceDetect--isIE .Theme-TextOverMediaSection .InlineMedia--image .Lazyload__loading,.DeviceDetect--isIE .Theme-TitleSection .InlineMedia--image .Lazyload__loading,.nav-item-promo~.nav-item-promo,.shorthand_story-template-default:before,figure[class*=h-align-] .Theme-Lazyload-Spinner,figure[class*=media-size-] .Theme-Lazyload-Spinner{display:none}.Videoplayer--responsive{background-color:#000}.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 40px);top:50%;-webkit-transform:translateY(-50%);transform:translateY(-50%)}@media (min-width:620px){.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 50px)}}@media (min-width:1100px){.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 94px)}}.CardCanvasItem>a:after,.Theme-Layer-BodyText .InlineMedia--image>a:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:after,.Theme-Layer-ResponsiveMedia-image>a:after{content:"";position:absolute;background:rgba(0,0,0,.35) url(data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAADYAAAA2CAMAAAC7m5rvAAAADFBMVEX////////////////1pQ5zAAAABHRSTlMB/I1CoQ5N8QAAAM5JREFUeNrN1kEKwzAQQ9Fauv+duzCJalwy83EX1c7gZ0LGEXn9IpaNzZgRUhp33FfjM2Iqjqk4pCTglq1tp2wEztlG3L6pMz9Hbe6BKWpzqpi/Pzliceghw9x4JTnHF+sPYC5cMsfNVaLW5doZu8oZN3FRwDmL9FnvQ90P0aNbo7rPRhkduKJggfM6B9Bnts/7jDuPxKTPEqE+C8N9lvNZn+lScfrDPktYnyWozxLYZzPmfbaOGzif9ZnZj0cUcFGtMJUwlYgpMuWiz07zBirwBIVbSDEiAAAAAElFTkSuQmCC) 6px center no-repeat;background-size:18px auto;color:transparent;border-radius:5px;top:5px;right:5px;z-index:1;width:30px;height:30px;line-height:30px;overflow:hidden;font-size:11px;text-align:left;text-transform:uppercase;font-weight:700;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Helvetica,Arial,sans-serif,"Apple Color Emoji","Segoe UI Emoji","Segoe UI Symbol";-webkit-transition:width .15s ease,color .15s ease .15s;transition:width .15s ease,color .15s ease .15s}@media (hover:none) and (pointer:coarse){.CardCanvasItem>a:after,.Theme-Layer-BodyText .InlineMedia--image>a:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:after,.Theme-Layer-ResponsiveMedia-image>a:after{content:"Visit link";color:#fff;width:96px;padding-left:29px;background-color:rgba(0,0,0,.75)}}.CardCanvasItem>a:hover:after,.Theme-Layer-BodyText .InlineMedia--image>a:hover:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:hover:after,.Theme-Layer-ResponsiveMedia-image>a:hover:after{content:"Visit link";color:#fff;width:96px;padding-left:29px;background-color:rgba(0,0,0,.75)}.DeviceDetect--isIE .Theme-Layer-BodyText .InlineMedia--image .FullSize,.DeviceDetect--isIE .Theme-TextOverMediaSection .InlineMedia--image .FullSize,.DeviceDetect--isIE .Theme-TitleSection .InlineMedia--image .FullSize{position:relative;top:auto;left:auto}@media (min-width:900px){.DisplayContainerHeight--flex.Display--md-block{display:-webkit-box!important;display:-ms-flexbox!important;display:flex!important}}[dir=rtl]{direction:rtl}.Theme-TextOverMediaSection .InlineMedia .Lazyload__loading,.Theme-TitleSection .InlineMedia .Lazyload__loading{opacity:0!important}body:not(.body-editor) .Theme-Layer-BodyText-QuoteCite:empty{display:none}.Theme-Section-Layout--Full .Theme-BackgroundImage .FullSize--fixedChild{clip-path:none;-webkit-clip-path:none}#td-outer-wrap,.shorthand_story-template-default .overflow-container{overflow:initial}@media (max-width:960px){.shorthand_story-template-default #main-sidebar{padding:1.5em}.shorthand_story-template-default #main{padding:0}}.shorthand-embed-article,.shorthand-embed-body,.shorthandLoader-Container{min-height:100vh!important}.shorthand-embed-article .FullSize,.shorthand-embed-article .FullSize--basic{height:100%}.shorthand-embed-article .Theme-Overlay.FullSize{min-height:100%}.shorthand-embed-article .Theme-Section{width:100%}.shorthand-embed-article .Theme-Section:not(.Theme-TitleSection) .DisplayContainerHeight:not(.DisplayContainerHeight--flex){height:100vh}.shorthand-embed-body article{overflow:initial!important;padding:0}.shorthand-embed-body .Theme-Navigation-ItemList:empty{display:none}@media print{body,html{height:auto}abbr[title]:after{content:" (" attr(title) ")"}blockquote,pre,tr{page-break-inside:avoid}thead{display:table-header-group}h2,h3,p{orphans:3;widows:3}.Theme-Layer-BodyText a[href^="#"]:after,.Theme-Layer-BodyText a[href^="javascript:"]:after{content:""}.Theme-Layer-BodyText a[href]:after{content:" (" attr(href) ")"}.Theme-Section.DisplayContainerHeight,.Theme-Section.DisplayContainerHeight--minHeight{height:0!important;min-height:0!important;padding-top:52.65%}.FullSize--fullHeight,.Theme-Item-MediaRenderer aside,.Theme-Item-MediaRenderer img{display:block;height:100%;position:absolute;top:0;left:0;right:0;bottom:0}.DisplayContainerHeight{height:100%}.DisplayContainerHeight--minHeight{min-height:100%}.FullSize--fixedChild .FullSize__fixedChild{position:absolute;-o-object-fit:cover;object-fit:cover;top:0;left:0;right:0;bottom:0}.Theme-Story .PositionSticky{position:relative!important}.CardCanvas--tworowContainer .CardCanvas__canvasColumn{display:none}.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:2em}.MediaRenderer__fixedCaption{position:absolute}.Theme-Item-MediaRenderer{height:100%!important;position:absolute;top:0;left:0;right:0;bottom:0}.Theme-Item-MediaRenderer aside,.Theme-Item-MediaRenderer img{width:100%}.Theme-Footer,.Theme-RevealSection{display:none}.Theme-BackgroundScrollmationSection.DisplayContainerHeight,.Theme-BackgroundScrollmationSection.DisplayContainerHeight--minHeight{height:auto!important;min-height:auto!important;padding-top:0}.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{margin-top:0!important;margin-bottom:0!important}.Lazyload__loading{display:none!important}.Theme-Item-Picture,[data-lazyload-item]{position:relative!important;height:auto!important;top:auto!important;left:auto!important}.BackgroundScrollmationItem img,[data-lazyload-item] img{opacity:1!important}.BackgroundScrollmation{height:auto!important}.BackgroundScrollmationItem{width:100%!important;display:block!important;opacity:1!important;bottom:auto!important;right:auto!important}.BackgroundScrollmationItem,.BackgroundScrollmationItem .FullSize{position:relative!important;height:auto!important;top:auto!important}.Theme-Layer-BodyText .InlineMedia img{max-width:50%}.Theme-FooterTopLink,.Theme-HeaderContainer{display:none!important}}.Theme-ForegroundColor-0{color:#19af90}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-0,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-0,.text-edit-dropdown-colour.Theme-BackgroundColor-0,.text-edit-dropdown-colour.Theme-ForegroundColor-0{background:#19af90}.Theme-BackgroundColor-0{background-color:#19af90}.Theme-ForegroundColor-1{color:#00a7cf}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-1,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-1,.text-edit-dropdown-colour.Theme-BackgroundColor-1,.text-edit-dropdown-colour.Theme-ForegroundColor-1{background:#00a7cf}.Theme-BackgroundColor-1{background-color:#00a7cf}.Theme-ForegroundColor-2{color:#f2744d}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-2,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-2,.text-edit-dropdown-colour.Theme-BackgroundColor-2,.text-edit-dropdown-colour.Theme-ForegroundColor-2{background:#f2744d}.Theme-BackgroundColor-2{background-color:#f2744d}.Theme-ForegroundColor-3{color:#ccb87e}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-3,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-3,.text-edit-dropdown-colour.Theme-BackgroundColor-3,.text-edit-dropdown-colour.Theme-ForegroundColor-3{background:#ccb87e}.Theme-BackgroundColor-3{background-color:#ccb87e}.Theme-ForegroundColor-4{color:#aaa}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-4,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-4,.text-edit-dropdown-colour.Theme-BackgroundColor-4,.text-edit-dropdown-colour.Theme-ForegroundColor-4{background:#aaa}.Theme-BackgroundColor-4{background-color:#aaa}.Theme-ForegroundColor-5{color:#777}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-5,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-5,.text-edit-dropdown-colour.Theme-BackgroundColor-5,.text-edit-dropdown-colour.Theme-ForegroundColor-5{background:#777}.Theme-BackgroundColor-5{background-color:#777}.Theme-ForegroundColor-6{color:#424242}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-6,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-6,.text-edit-dropdown-colour.Theme-BackgroundColor-6,.text-edit-dropdown-colour.Theme-ForegroundColor-6{background:#424242}.Theme-BackgroundColor-6{background-color:#424242}.Theme-ForegroundColor-7{color:#ec3f3f}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-7,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-7,.text-edit-dropdown-colour.Theme-BackgroundColor-7,.text-edit-dropdown-colour.Theme-ForegroundColor-7{background:#ec3f3f}.Theme-BackgroundColor-7{background-color:#ec3f3f}.Theme-ForegroundColor-8{color:#8ac064}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-8,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-8,.text-edit-dropdown-colour.Theme-BackgroundColor-8,.text-edit-dropdown-colour.Theme-ForegroundColor-8{background:#8ac064}.Theme-BackgroundColor-8{background-color:#8ac064}.Theme-ForegroundColor-9{color:#fff}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-9,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-9,.text-edit-dropdown-colour.Theme-BackgroundColor-9,.text-edit-dropdown-colour.Theme-ForegroundColor-9{background:#fff}.Theme-BackgroundColor-9{background-color:#fff}.Theme-ForegroundColor-10{color:#000}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-10,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-10,.text-edit-dropdown-colour.Theme-BackgroundColor-10,.text-edit-dropdown-colour.Theme-ForegroundColor-10{background:#000}.Theme-BackgroundColor-10{background-color:#000}.Theme-ForegroundColor-11{color:#93d6c7}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-11,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-11,.text-edit-dropdown-colour.Theme-BackgroundColor-11,.text-edit-dropdown-colour.Theme-ForegroundColor-11{background:#93d6c7}.Theme-BackgroundColor-11{background-color:#93d6c7}.Theme-ForegroundColor-12{color:#8cd3e6}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-12,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-12,.text-edit-dropdown-colour.Theme-BackgroundColor-12,.text-edit-dropdown-colour.Theme-ForegroundColor-12{background:#8cd3e6}.Theme-BackgroundColor-12{background-color:#8cd3e6}.Theme-ForegroundColor-13{color:#f7b9a9}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-13,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-13,.text-edit-dropdown-colour.Theme-BackgroundColor-13,.text-edit-dropdown-colour.Theme-ForegroundColor-13{background:#f7b9a9}.Theme-BackgroundColor-13{background-color:#f7b9a9}.Theme-ForegroundColor-14{color:#e5dbc0}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-14,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-14,.text-edit-dropdown-colour.Theme-BackgroundColor-14,.text-edit-dropdown-colour.Theme-ForegroundColor-14{background:#e5dbc0}.Theme-BackgroundColor-14{background-color:#e5dbc0}.Theme-ForegroundColor-15{color:#f4a0a1}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-15,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-15,.text-edit-dropdown-colour.Theme-BackgroundColor-15,.text-edit-dropdown-colour.Theme-ForegroundColor-15{background:#f4a0a1}.Theme-BackgroundColor-15{background-color:#f4a0a1}.Theme-ForegroundColor-16{color:#c5dfb4}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-16,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-16,.text-edit-dropdown-colour.Theme-BackgroundColor-16,.text-edit-dropdown-colour.Theme-ForegroundColor-16{background:#c5dfb4}.Theme-BackgroundColor-16{background-color:#c5dfb4}.Theme-BackgroundColor-17{background-color:transparent}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-17,.text-edit-dropdown-colour.Theme-BackgroundColor-17{background:0 0} /*-->*/ " + "ipt>"); } })(navigator, 'userAgent', 'appVersion', 'script', document); //--> Shorthand Story Body:  Inflatable, shape-changing spinal implants could help treat severe pain a{display:block;-webkit-transition:opacity .15s ease;transition:opacity .15s ease}.Theme-LinkedMediaRenderer{display:block}.InlineMedia a:active,.InlineMedia a:focus,.InlineMedia a:hover,.Theme-LinkedMediaRenderer:active,.Theme-LinkedMediaRenderer:focus,.Theme-LinkedMediaRenderer:hover,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:active,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:focus,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a:hover{cursor:pointer;opacity:.9}.Theme-HeaderContainer{font-size:18px}.Theme-HeaderContainer,.Theme-Story{font-family:"PT Serif",serif;color:#333;-webkit-font-smoothing:antialiased;-moz-osx-font-smoothing:grayscale}.Theme-HeaderContainer ::-moz-selection{color:inherit;background-color:rgba(160,160,160,.55)}.Theme-Story ::-moz-selection{background-color:rgba(160,160,160,.55)}.Theme-HeaderContainer ::selection{color:inherit}.Theme-HeaderContainer ::selection,.Theme-Story ::selection{background-color:rgba(160,160,160,.55)}@media (min-width:900px){.Theme-HeaderContainer,.Theme-Story{font-size:18px}}@media (min-width:1100px){.Theme-HeaderContainer,.Theme-Story{font-size:20px}}@media (max-width:1400px){.Layout{width:auto}}@media (max-width:620px){.Theme-Layer-BodyText{width:100%}}.Theme-Layer-BodyText p,.Theme-Story p{display:block;margin-top:1.5rem;margin-bottom:1.5rem;line-height:1.7;font-family:"PT Serif",serif;font-weight:400;font-size:inherit}.Theme-OverlayedCaption a,.Theme-Section-Dark .Theme-Caption a,.Theme-Section-Dark .Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a,.Theme-Section[class*=Theme-ForegroundColor] a:not(.Theme-Layer-BodyText-Button){text-decoration:none;border-bottom:1px dotted}.Theme-Caption a,.Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a{text-decoration:none;border-bottom:1px dotted;color:#00a7cf}.Theme-OverlayedCaption a:hover,.Theme-Section[class*=Theme-ForegroundColor] a:hover:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:hover,.Theme-Layer-BodyText a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:hover{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:active,.Theme-Section[class*=Theme-ForegroundColor] a:active:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:active,.Theme-Layer-BodyText a:active:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:active{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:focus,.Theme-Section[class*=Theme-ForegroundColor] a:focus:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:focus,.Theme-Layer-BodyText a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:focus{color:#007e9c;border-bottom-style:solid}.Theme-Caption a:visited,.Theme-Layer-BodyText a:visited:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited{color:#03ceff}.Theme-OverlayedCaption a:visited:hover,.Theme-Section[class*=Theme-ForegroundColor] a:visited:hover:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:hover,.Theme-Layer-BodyText a:visited:hover:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:hover{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:visited:active,.Theme-Section[class*=Theme-ForegroundColor] a:visited:active:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:active,.Theme-Layer-BodyText a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:active{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a:visited:focus,.Theme-Section[class*=Theme-ForegroundColor] a:visited:focus:not(.Theme-Layer-BodyText-Button){border-bottom-style:solid}.Theme-Caption a:visited:focus,.Theme-Layer-BodyText a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Layer-TextBlock-Inner a:visited:focus{color:#007e9c;border-bottom-style:solid}.Theme-OverlayedCaption a,.Theme-Section-Dark .Theme-Caption a,.Theme-Section-Dark .Theme-Layer-BodyText a:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a{color:#00a7cf}.Theme-OverlayedCaption a:active,.Theme-OverlayedCaption a:focus,.Theme-OverlayedCaption a:hover,.Theme-Section-Dark .Theme-Caption a:active,.Theme-Section-Dark .Theme-Caption a:focus,.Theme-Section-Dark .Theme-Caption a:hover,.Theme-Section-Dark .Theme-Layer-BodyText a:active:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:hover{color:#03ceff}.Theme-OverlayedCaption a:visited,.Theme-Section-Dark .Theme-Caption a:visited,.Theme-Section-Dark .Theme-Layer-BodyText a:visited:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited{color:#007e9c}.Theme-OverlayedCaption a:visited:active,.Theme-OverlayedCaption a:visited:focus,.Theme-OverlayedCaption a:visited:hover,.Theme-Section-Dark .Theme-Caption a:visited:active,.Theme-Section-Dark .Theme-Caption a:visited:focus,.Theme-Section-Dark .Theme-Caption a:visited:hover,.Theme-Section-Dark .Theme-Layer-BodyText a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-BodyText a:visited:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited:hover{color:#03ceff}.Theme-Section[class*=Theme-ForegroundColor] a:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit}.Theme-Section[class*=Theme-ForegroundColor] a:active:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:hover:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:active:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:focus:not(.Theme-Layer-BodyText-Button),.Theme-Section[class*=Theme-ForegroundColor] a:visited:hover:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit;opacity:.8}.Theme-Section[class*=Theme-ForegroundColor] a:visited:not(.Theme-Layer-BodyText-Button){color:inherit;border-bottom-color:inherit}.GalleryRenderer--initializing:after,.Theme-Lazyload-Spinner{position:absolute;top:50%;left:50%;width:26px;height:26px;margin-left:-13px;margin-top:-13px;border-radius:50%;border:4px solid #fff;border-bottom-color:transparent;-webkit-animation:loading-spinner forwards 1s linear infinite;animation:loading-spinner forwards 1s linear infinite;background:rgba(0,0,0,.5);-webkit-box-shadow:0 0 0 4px rgba(0,0,0,.5);box-shadow:0 0 0 4px rgba(0,0,0,.5)}.Theme-Lazyload-Spinner{opacity:.25}.Theme-Story{display:block;background-color:#fff;font-size:17px}@media (min-width:620px){.Theme-Story{font-size:18px}}@media (min-width:900px){.Theme-Story{font-size:18px}}@media (min-width:1100px){.Theme-Story{font-size:20px}}@media (min-width:1400px){.Theme-Story{font-size:20px}}@media (min-width:1750px){.Theme-Story{font-size:22px}}@media (min-width:2000px){.Theme-Story{font-size:22px}}.Theme-Story ::-moz-selection{background-color:#00a7cf;color:#fff}.Theme-Story ::selection{background-color:#00a7cf;color:#fff}.Theme-Story p{width:100%;color:inherit}.Theme-Story sub,.Theme-Story sup{font-size:70%;display:inline-block;line-height:1.7}.Theme-Story sub+a,.Theme-Story sup+a{margin-left:.25em}.Theme-Story sup{top:-.5em}.Theme-Story sub{bottom:-.25em}.Theme-Layer-BodyText-Heading-Large,.Theme-Layer-BodyText-Heading-Small,.Theme-Layer-BodyText-Heading-xs{display:block;width:100%}.Theme-Layer-BodyText-Heading-Large{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:150%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-Large{font-size:160%}}.Theme-Layer-BodyText-Heading-Small{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:130%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-Small{font-size:140%}}.Theme-Layer-BodyText-Heading-xs{color:#333;margin-top:1.5rem;margin-bottom:1.5rem;font-family:inherit;font-weight:400;font-size:120%;line-height:1.3}@media (min-width:620px){.Theme-Layer-BodyText-Heading-xs{font-size:130%}}.Theme-Layer-BodyText-List-Alpha,.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Roman,.Theme-Layer-BodyText-List-Unordered{padding-left:1.2rem;list-style-position:outside;font-size:inherit;font-weight:400;color:#333;margin-top:1.5rem;margin-bottom:1.5rem}.Theme-Layer-BodyText-List-Alpha{list-style-type:lower-alpha}.Theme-Layer-BodyText-List-Roman{list-style-type:lower-roman}.Theme-Layer-BodyText-List-Unordered{list-style-type:square}.Theme-Layer-BodyText-ListItem{line-height:1.7;margin-bottom:.5rem;font-family:"PT Serif",serif}.Theme-Layer-BodyText-Blockquote{display:block;padding-top:1.5rem;padding-bottom:1.5rem;padding-right:1.5rem;border-top:2px solid rgba(204,204,204,.3);border-bottom:2px solid rgba(204,204,204,.3);margin-top:1.5rem;margin-bottom:1.5rem;color:#777;font-family:"PT Serif",serif;font-weight:400;font-style:italic;font-size:120%;line-height:1.4}@media (min-width:620px){.Theme-Layer-BodyText-Blockquote{font-size:130%}}.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{display:block;margin:1rem 0 .5rem;font-family:"Lato",sans-serif;color:#777;line-height:1.2;font-style:normal;font-weight:400;font-size:13.6px}@media (min-width:620px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:14.4px}}@media (min-width:900px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:14.4px}}@media (min-width:1100px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:16px}}@media (min-width:1400px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:16px}}@media (min-width:1750px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:17.6px}}@media (min-width:2000px){.Theme-Caption cite,.Theme-Layer-BodyText-QuoteCite{font-size:17.6px}}div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{display:block;float:left;max-width:100%;font-family:inherit;font-size:5.7em;font-style:inherit;font-weight:inherit;line-height:.825;margin-right:.05em;margin-top:0;margin-bottom:0}@media (min-width:620px){div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{font-size:5.7em}}.Theme-Layer-BodyText-Breakout{border:1px solid #333;background:rgba(255,255,255,.2);padding:25px}@media (min-width:620px){.Theme-Layer-BodyText-Breakout{padding:30px}}@media (min-width:1100px){.Theme-Layer-BodyText-Breakout{padding:40px}}.Theme-Layer-BodyText-Indent{border-left:4px solid rgba(51,51,51,.1);padding-left:25px}@media (min-width:620px){.Theme-Layer-BodyText-Indent{padding-left:30px}}@media (min-width:1100px){.Theme-Layer-BodyText-Indent{padding-left:40px}}.Theme-Story .Theme-Layer-BodyText-Highlight{background-color:rgba(51,51,51,.2)}.Theme-Story .Theme-Layer-BodyText-Highlight:hover{background-color:rgba(51,51,51,.4)}.Theme-Story .Theme-Layer-BodyText-Highlight:focus{background-color:rgba(51,51,51,.4);outline:#333 auto 1px}.Theme-Story .Theme-Layer-BodyText-Highlight .Theme-Layer-BodyText-Highlight--Icon{background-color:#333}.Theme-Story .Theme-Footnote{font-family:"PT Serif",serif;font-size:80%;line-height:1.5;color:#222;background-color:rgba(255,255,255,.95);-webkit-box-shadow:0 3px 10px 6px rgba(0,0,0,.1),0 0 0 1px rgba(0,0,0,.1);box-shadow:0 3px 10px 6px rgba(0,0,0,.1),0 0 0 1px rgba(0,0,0,.1)}.Theme-Story .Theme-Footnote:after{border-color:rgba(255,255,255,.95) transparent transparent}.Theme-Story .Theme-Footnote:before{content:"";position:absolute;top:100%;height:20px;width:100%;z-index:-1;left:0}.Theme-Story .Theme-Footnote a{color:inherit}.Theme-Story .Theme-Footnote.Theme-Position-Top:after{border-color:transparent transparent rgba(255,255,255,.95)}.Theme-Overlay{z-index:1;opacity:0;-webkit-transform:translateZ(0);transform:translateZ(0)}.Theme-Overlay.FullSize{top:-2px;bottom:-2px;height:auto;left:-2px;right:-2px;width:auto}.Theme-Layer-TextBlock-Inner{pointer-events:auto;font-family:"Lato",sans-serif;padding-left:env(safe-area-inset-left);padding-right:env(safe-area-inset-right);font-size:100%;width:100%}@media (min-width:750px){.Theme-Layer-TextBlock-Inner{width:90%}}@media (orientation:landscape) and (max-width:900px){.Theme-Layer-TextBlock-Inner{width:60%}}@media (min-width:900px){.Theme-Layer-TextBlock-Inner{max-width:750px}}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner{max-width:850px}}@media (min-width:1400px){.Theme-Layer-TextBlock-Inner{max-width:1100px}}@media (min-width:1750px){.Theme-Layer-TextBlock-Inner{max-width:1250px}}@media (min-width:900px){.Theme-Section:not(.Theme-Section-Layout--Half) .Layout__flex--xleft .Theme-Layer-TextBlock-Inner,.Theme-Section:not(.Theme-Section-Layout--Half) .Layout__flex--xright .Theme-Layer-TextBlock-Inner{width:60%}}.Theme-Layer-TextBlock-Inner a{color:#333}.Theme-Layer-TextBlock-Inner a:active,.Theme-Layer-TextBlock-Inner a:focus,.Theme-Layer-TextBlock-Inner a:hover{color:#333}.Theme-Layer-TextBlock-Inner a:visited{color:#333}.Theme-Layer-TextBlock-Inner .Theme-Title{color:#333;font-weight:400}.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-Title{text-transform:none;display:block;margin:0;padding:0;line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{text-transform:none;display:block;color:#333;margin:0;padding:0;line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-Byline{text-transform:none;display:block;margin:0;padding:0}.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner .ProseMirror .Empty-Block .NodeContent>:after,.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Layer-TextBlock-Inner .Theme-Title{padding-left:40px;padding-right:40px}}.Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-StoryTitle{color:#333;font-family:"Lato",sans-serif;font-weight:400}.Theme-Layer-TextBlock-Inner .Theme-Byline{color:#777;line-height:1.1;font-size:.9em}.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{margin-top:.5rem}@media (min-width:1100px){.Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{margin-top:1rem}}.Theme-Layer-TextBlock-Inner .Theme-LeadIn:first-child,.Theme-Layer-TextBlock-Inner .Theme-SubTitle:first-child,.Theme-Layer-TextBlock-Inner .Theme-Text:first-child{margin-top:0}.Theme-Layer-TextBlock-Inner .Theme-Title{font-family:"Lato",sans-serif}.Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Layer-TextBlock-Inner .Theme-Text{font-family:inherit;font-weight:400}.InlineElement--Divider__container{display:-webkit-box;display:-ms-flexbox;display:flex;text-align:center;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center}.Theme-Layer-BodyText-Divider{display:inline-block;border:none;background-color:rgba(204,204,204,.75);height:2px;margin:2.1rem 0;overflow:hidden;width:50%}.Theme-Layer-BodyText-Button{display:inline-block;border:none;color:#fff;font-family:"Lato",sans-serif;font-weight:700;line-height:1.1;background:#00a7cf;font-size:90%;text-transform:initial;padding:.7em 1.4em;border-radius:.35em;cursor:pointer;margin-top:1.5rem;margin-bottom:1.5rem;text-decoration:none}.body-editor .Theme-Layer-BodyText-Button{color:#fff!important}.Theme-Layer-BodyText-Button:active,.Theme-Layer-BodyText-Button:focus,.Theme-Layer-BodyText-Button:hover{opacity:.9;text-decoration:none}.InlineMedia{text-align:center}.InlineMedia img{width:auto;height:auto;max-width:100%;margin:0 auto;display:inline-block}.InlineMedia.media-size-110 img{width:calc(100% + 50px)!important;max-width:calc(100% + 50px)!important;-webkit-transform:translate(-25px);transform:translate(-25px)}@media (min-width:620px){.InlineMedia.media-size-110 img{width:calc(100% + 60px)!important;max-width:calc(100% + 60px)!important;-webkit-transform:translate(-30px);transform:translate(-30px)}}@media (min-width:1100px){.InlineMedia.media-size-110 img{width:calc(100% + 80px)!important;max-width:calc(100% + 80px)!important;-webkit-transform:translate(-40px);transform:translate(-40px)}}.InlineMedia.media-size-100 img{width:100%!important;max-width:100%!important}.InlineMedia.media-size-90 img{width:90%!important;max-width:90%!important}.InlineMedia.media-size-80 img{width:80%!important;max-width:80%!important}.InlineMedia.media-size-70 img{width:70%!important;max-width:70%!important}.InlineMedia.media-size-60 img{width:60%!important;max-width:60%!important}.InlineMedia.media-size-50 img{width:50%!important;max-width:50%!important}.InlineMedia.media-size-40 img{width:40%!important;max-width:40%!important}.InlineMedia.media-size-30 img{width:30%!important;max-width:30%!important}.InlineMedia.media-size-20 img{width:20%!important;max-width:20%!important}.InlineMedia.media-size-10 img{width:10%!important;max-width:10%!important}.InlineMedia--image>a,.InlineMedia--image__inner>div a{border:none!important}.InlineMedia--image__inner{display:inline-block;font-size:0;max-width:100%}.InlineMedia--video video{width:100%}.Theme-Layer-BodyText{font-family:"PT Serif",serif;padding-top:calc(48px - 1.5rem);padding-bottom:48px;padding-left:25px;padding-right:25px}@media (max-width:619px){.Theme-Layer-BodyText{overflow:hidden}}@media (min-width:620px){.Theme-Layer-BodyText{padding-top:calc(60px - 1.5rem);padding-bottom:60px;padding-left:30px;padding-right:30px}}@media (min-width:900px){.Theme-Layer-BodyText{padding-top:calc(72px - 1.5rem)}}@media (min-width:1100px){.Theme-Layer-BodyText{padding-left:40px;padding-right:40px}}.Theme-Layer-BodyText .Theme-Overlay{position:absolute;top:0;left:0;right:0;bottom:0;z-index:-1}.Theme-Layer-BodyText p,.Theme-Layer-BodyText-Blockquote,.Theme-Layer-BodyText-Heading-Large,.Theme-Layer-BodyText-Heading-Small,.Theme-Layer-BodyText-Heading-xs,.Theme-Layer-BodyText-List-Alpha,.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Roman,.Theme-Layer-BodyText-List-Unordered,.Theme-Layer-BodyText-QuoteCite{margin-left:auto;margin-right:auto;text-transform:initial}.Theme-ButtonSize-xsmall .Theme-Layer-BodyText-Button{font-size:70%}.Theme-ButtonSize-small .Theme-Layer-BodyText-Button{font-size:80%}.Theme-ButtonSize-medium .Theme-Layer-BodyText-Button{font-size:90%}.Theme-ButtonSize-large .Theme-Layer-BodyText-Button{font-size:100%}.Theme-ButtonSize-xlarge .Theme-Layer-BodyText-Button{font-size:110%}.Theme-DividerSize-xlarge{width:100%}.Theme-DividerSize-xlarge+.InlineElement--UI__container .BlockBar-Align{display:none}.Theme-DividerSize-large{width:75%}.Theme-DividerSize-medium{width:50%}.Theme-DividerSize-small{width:25%}.Theme-DividerSize-xsmall{width:10%}.Theme-Layer-BodyText-Spacer,.Theme-SpacerSize-10{height:40px}.Theme-SpacerSize-20{height:80px;height:8vh}.Theme-SpacerSize-30{height:120px;height:16vh}.Theme-SpacerSize-40{height:180px;height:24vh}.Theme-SpacerSize-50{height:220px;height:32vh}.Theme-SpacerSize-60{height:280px;height:40vh}.Theme-SpacerSize-70{height:320px;height:50vh}.Theme-SpacerSize-80{height:360px;height:65vh}.Theme-SpacerSize-90{height:400px;height:85vh}.Theme-SpacerSize-100{height:440px;height:100vh}.Theme-Caption .caption-editor-empty{font-family:"Lato",sans-serif;font-size:.8em;font-weight:400;line-height:1.2;margin:0}.Theme-Caption cite,.Theme-Caption p:not(:empty){margin:0;max-width:100%}.Theme-Caption p:not(:empty){color:#777;font-weight:400;font-family:"Lato",sans-serif;font-style:normal;line-height:1.2;font-size:.8em;padding:.5em}.Theme-Caption [contenteditable=false],.Theme-Caption cite{padding:.5em}.Theme-Caption a{display:inline}.Theme-OverlayedCaption{background-color:rgba(34,34,34,.65);z-index:2}.Theme-CollectionSectionSection .Theme-OverlayedCaption,.Theme-TextOverMediaSection .Theme-OverlayedCaption,.Theme-TitleSection .Theme-OverlayedCaption{position:absolute;bottom:0;left:0;right:0}.Theme-OverlayedCaption p:not(:empty){color:rgba(255,255,255,.7);font-family:"Lato",sans-serif;font-size:.8em;line-height:1.2;margin:0;padding:.5em 25px}.Theme-OverlayedCaption [contenteditable=false]{padding:.5em 25px}.DisplayContainerHeight--heightThird .Theme-OverlayedCaption [contenteditable=false],.DisplayContainerHeight--heightThird .Theme-OverlayedCaption p:not(:empty){font-size:12px}@media (min-width:620px){.Theme-OverlayedCaption [contenteditable=false],.Theme-OverlayedCaption p:not(:empty){padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-OverlayedCaption [contenteditable=false],.Theme-OverlayedCaption p:not(:empty){padding-left:40px;padding-right:40px}}.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-MediaSection .Theme-Caption [contenteditable=false],.Theme-MediaSection .Theme-Caption p:not(:empty){padding-left:40px;padding-right:40px}}.Theme-ImageCaption,.Theme-InlineMediaCaption p{text-align:center}.h-align-right .Theme-InlineMediaCaption p{text-align:right;padding-right:0}.h-align-left .Theme-InlineMediaCaption p{text-align:left;padding-left:0}.Theme-ImageCaption p:not(:empty),.Theme-InlineMediaCaption p:not(:empty){color:#777}.Theme-HeaderContainer{height:40px;background:#fff;-webkit-box-shadow:0 2px 2px -2px rgba(0,0,0,.3);box-shadow:0 2px 2px -2px rgba(0,0,0,.3)}@media (min-width:900px){.Theme-HeaderContainer{height:50px}}@media (min-width:1100px){.Theme-HeaderContainer{height:60px}}.Theme-HeaderContainer.Theme-Section-Custom{-webkit-box-shadow:none;box-shadow:none}.Theme-HeaderContainer .Theme-Header{width:100%;max-width:100%;padding-left:env(safe-area-inset-left);padding-right:env(safe-area-inset-right)}.Theme-Logos{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex;height:32px;margin-left:15px}@media (min-width:900px){.Theme-Logos{height:38px}}@media (min-width:1100px){.Theme-Logos{height:44px}}.Theme-Logo{display:inline-block;vertical-align:top;width:100%;min-width:auto;height:100%;margin-right:calc(10px + .5vw)}.body-editor .Theme-Logo{display:-webkit-box;display:-ms-flexbox;display:flex}.Theme-Logo a{display:block;height:100%}.Theme-Logo img{max-height:100%;max-width:none;width:auto;-ms-flex-negative:0;flex-shrink:0}.Theme-Default-Logos,.Theme-SocialIcons{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex}.Theme-Default-Logos,.Theme-Logo img{vertical-align:top;height:100%}.DeviceDetect--isIE .Theme-Default-Logos .Theme-Logo{min-width:100%}.Theme-SocialIcons{position:absolute;min-width:80px;height:32px;top:50%;margin-top:-16px;-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end;text-align:right;right:0;margin-right:15px}@media (min-width:1100px){.Theme-SocialIcons{position:absolute}}@media (max-width:1099px){.Theme-Hamburger~.Theme-SocialIcons{right:45px;right:calc(45px + env(safe-area-inset-right))}}.Theme-SocialButton{display:inline-block;vertical-align:top;margin-left:4px}.Theme-SocialButton a{display:block;border-radius:4px;overflow:hidden;width:32px;height:32px}.Theme-SocialButton a:after{content:"";display:block;position:absolute;top:0;left:0;right:0;bottom:0}.Theme-NavigationBar.Theme-NavigationBar-Sticky:before,.Theme-NavigationBar.Theme-Section-Custom:before,.Theme-NavigationBar.Theme-Section-Dark:before,.Theme-SocialButton img{display:none}.Theme-TwitterButton{background:#00aced}.Theme-TwitterButton:after{background:url(data:image/png;base64,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) center no-repeat;background-size:18px auto;background-position-y:-20px}.Theme-FaceboookButton{background-color:#3b5998}.Theme-FaceboookButton:after{background:url(data:image/png;base64,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) center no-repeat;background-size:8px auto;background-position-y:-19px}.Theme-Hamburger{right:15px;right:calc(15px + env(safe-area-inset-right))}.Theme-Hamburger span{background:#333;height:3px}.Theme-NavigationBar{top:40px;background-color:rgba(34,34,34,.9);color:rgba(255,255,255,.6);width:100%;max-width:none;overflow-y:auto;-webkit-backdrop-filter:blur(5px);backdrop-filter:blur(5px)}@media (max-width:619px){.Theme-NavigationBar{min-width:100%}}@media (min-width:620px) and (max-width:1099px){.Theme-NavigationBar{max-width:400px}}@media (max-width:1099px){.Theme-NavigationBar{padding-bottom:40px}}@media (min-width:900px){.Theme-NavigationBar{top:50px}}@media (min-width:1100px){.Theme-NavigationBar{top:100%;position:absolute;left:0;right:0;padding:0 15px;display:block;-webkit-backdrop-filter:none;backdrop-filter:none;overflow:hidden}}@media (max-width:1099px){#Navigation__hamburgerToggle:checked~.Theme-NavigationBar{right:-15px}}@media (max-width:619px){#Navigation__hamburgerToggle:checked~.Theme-NavigationBar{left:-15px}}.Theme-NavigationBar.Theme-NavigationBar-Sticky,.Theme-NavigationBar.Theme-Section-Custom,.Theme-NavigationBar.Theme-Section-Dark{opacity:.95}.Theme-NavigationBar-Sticky{background:rgba(34,34,34,.9)}@media (min-width:1100px){.Theme-Navigation-ItemList{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;-ms-flex-wrap:wrap;flex-wrap:wrap}}.Theme-NavigationBarItem{padding:0;text-decoration:none;border-bottom:none;border-top:0 solid rgba(180,180,180,.4);color:inherit}.Theme-NavigationBarItem::after,.Theme-NavigationBarItem::before{display:none}@media (min-width:1100px){.Theme-NavigationBarItem{display:inline-block;border-top:none;margin:0}}.Theme-NavigationLink{font-family:"Lato",sans-serif;font-size:17px;font-weight:700;color:inherit;line-height:1;text-decoration:none;display:block;padding:15px;border:none}.Theme-NavigationLink:empty:before{content:"Untitled"}.Theme-ActiveNavigationBarItem .Theme-NavigationLink,.Theme-NavigationLink:active,.Theme-NavigationLink:hover{color:#fff;text-decoration:none}.Theme-NavigationLink:focus-within{color:#fff;text-decoration:none}@media (min-width:1100px){.Theme-NavigationLink{font-size:16px;padding:8px 10px;margin:0}}.Theme-Section-Custom .Theme-NavigationLink,.Theme-Section-Dark .Theme-NavigationLink{opacity:.6;color:inherit}.Theme-Section-Custom .Theme-NavigationLink:active,.Theme-Section-Custom .Theme-NavigationLink:hover,.Theme-Section-Dark .Theme-NavigationLink:active,.Theme-Section-Dark .Theme-NavigationLink:hover{color:inherit;opacity:1}.Theme-Section-Custom .Theme-NavigationLink:focus-within,.Theme-Section-Dark .Theme-NavigationLink:focus-within{color:inherit;opacity:1}.Theme-Section-Custom .Theme-ActiveNavigationBarItem .Theme-NavigationLink,.Theme-Section-Dark .Theme-ActiveNavigationBarItem .Theme-NavigationLink{color:inherit;opacity:1}@media (min-width:1100px){.Theme-SiteNavigationBar{overflow:visible}}.Theme-SiteNavigation-SubItemList{display:-webkit-box;display:-ms-flexbox;display:flex;padding:0;list-style:none}@media (max-width:1099px){.Theme-SiteNavigation-SubItemList{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column}}.Theme-MediaSection video,.Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink{width:100%}@media (min-width:1100px){.Theme-SiteNavigationBarSubItem:hover .Theme-SiteNavigation-ItemList--depth1 .Theme-SiteNavigation-SubItemList{height:auto;max-height:380px;min-width:200px;-webkit-transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;opacity:1;overflow-y:auto}.Theme-SiteNavigationBarSubItem:focus-within .Theme-SiteNavigation-ItemList--depth1 .Theme-SiteNavigation-SubItemList{height:auto;max-height:380px;min-width:200px;-webkit-transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;transition:max-height .15s ease-out .15s,opacity .15s ease-out .15s;opacity:1;overflow-y:auto}.Theme-SiteNavigationBarSubItem>ul{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start}.Theme-SiteNavigationBarSubItem>ul>li{width:100%;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigation-ItemList{-ms-flex-wrap:nowrap;flex-wrap:nowrap}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:after{content:"";display:inline-block;width:0;height:0;border-style:solid;border-width:6px 4px 0;border-color:rgba(255,255,255,.6) transparent transparent;margin-left:5px}.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:focus:after,.Theme-SiteNavigation-ItemList--depth1>li:first-child:not(:only-child) .Theme-SiteNavigationLink:hover:after{border-color:#fff transparent transparent}}@media (max-width:1099px){.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink{padding-left:35px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink:not(:hover){background:rgba(255,255,255,.1)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList .Theme-SiteNavigationLink:before{content:"";display:inline-block;width:10px;height:1px;background-color:rgba(255,255,255,.6);margin-left:-18px;margin-right:8px}}@media (min-width:1100px){.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList{opacity:0;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;position:absolute;width:0;top:100%;left:0;max-height:0;overflow:hidden;border-top:0 solid transparent;-webkit-transition:opacity .15s ease-out .15s;transition:opacity .15s ease-out .15s;scrollbar-width:thin;border-top-right-radius:3px;border-top-left-radius:3px;border-bottom-right-radius:3px;border-bottom-left-radius:3px;-webkit-box-shadow:0 8px 5px -5px rgba(0,0,0,.2);box-shadow:0 8px 5px -5px rgba(0,0,0,.2)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar{width:9px;height:9px;background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-track{background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-thumb{background:rgba(255,255,255,.6);width:5px;height:5px;border-radius:10px;border:2px solid rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList::-webkit-scrollbar-thumb:hover{background:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink{color:rgba(255,255,255,.6);font-weight:700;padding:10px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:active,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:hover,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:active,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:hover{color:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>.Theme-ActiveNavigationBarItem .Theme-SiteNavigationLink:focus-within,.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li .Theme-SiteNavigationLink:focus-within{color:#fff}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li{background:rgba(34,34,34,.9)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:not(:last-child){border-bottom:1px solid rgba(255,255,255,.1)}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:first-child{border-top:1px solid rgba(255,255,255,.1);border-top-right-radius:3px;border-top-left-radius:3px;padding-top:2px}.Theme-SiteNavigation-ItemList--depth1>li .Theme-SiteNavigation-SubItemList>li:last-child{border-bottom-right-radius:3px;border-bottom-left-radius:3px;padding-bottom:5px}}@media (max-width:1099px){.Theme-SiteNavigationBarItem:hover{background:0 0;text-decoration:none}}.Theme-SiteNavigationLink{text-align:left}@media (max-width:1099px){.Theme-SiteNavigationLink{text-align:left;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.Theme-SiteNavigationLink:hover{text-decoration:underline;background:rgba(255,255,255,.2)}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden{height:0}@media (max-width:1099px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden{background:0 0;height:auto;width:auto;display:-webkit-box;display:-ms-flexbox;display:flex;right:0;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end;-webkit-box-shadow:none;box-shadow:none}}.body-editor .Theme-HeaderContainer.Theme-HeaderContainer--hidden{top:0}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Logos{display:none}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-SocialIcons{display:none!important}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Header{width:100%;max-width:100%;height:0}@media (max-width:1099px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Header{max-width:50px;height:auto;max-height:50px;margin:0;background-color:#fff;-webkit-box-shadow:0 2px 2px -2px rgba(0,0,0,.3);box-shadow:0 2px 2px -2px rgba(0,0,0,.3)}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-Hamburger{margin:10px;position:relative;right:0;top:auto;-webkit-transform:none;transform:none}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar{top:0;border-top:50px solid #fff}}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar{position:absolute;top:100%;left:0;right:0;-webkit-transform:none;transform:none;margin:0}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationBar:not(.Theme-Section-Custom){background-color:rgba(34,34,34,.9)}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden .Theme-NavigationLink{padding:8px 10px}}.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:100vh}.body-editor .Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 60px)}@media (min-width:1100px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-Layer-CardCanvas[data-card-canvas]{margin-top:50px;top:50px}}@media (max-width:899px){.Theme-HeaderContainer.Theme-HeaderContainer--hidden+.Theme-Story .Theme-Layer-CardCanvas[data-card-canvas]{top:0}}@media (max-width:1099px){body:not(.body-editor) .Theme-HeaderContainer.Theme-HeaderContainer--hidden.Theme-HeaderContainer--navigable+.Theme-Story{margin-top:-50px}}.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{margin:0;padding-left:25px;padding-right:25px}@media (min-width:620px){.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-TextOverMediaSection .InlineMedia,.Theme-TitleSection .InlineMedia{padding-left:40px;padding-right:40px}}.Theme-TextOverMediaSection .InlineMedia img,.Theme-TitleSection .InlineMedia img{margin:5px auto;opacity:1}.Theme-TextOverMediaSection .InlineMedia--video,.Theme-TextOverMediaSection .InlineMedia--youTube,.Theme-TextOverMediaSection .InlineMedia-Soundcloud,.Theme-TextOverMediaSection .RichEmbed--soundcloud,.Theme-TextOverMediaSection .RichEmbed--youtube,.Theme-TitleSection .InlineMedia--video,.Theme-TitleSection .InlineMedia--youTube,.Theme-TitleSection .InlineMedia-Soundcloud,.Theme-TitleSection .RichEmbed--soundcloud,.Theme-TitleSection .RichEmbed--youtube{margin:.5rem 0}.DisplayContainerHeight--flex,.DisplayContainerHeight--flex .Layer--one{display:-webkit-box;display:-ms-flexbox;display:flex}.DisplayContainerHeight--flex .Layer--one{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-flex:1;-ms-flex:1;flex:1;width:100%;padding:calc(4vh + 40px) 0}.CardCanvas--tworowContainer .CardCanvasItem__image img,.DisplayContainerHeight--flex .DisplayContainerHeight{height:100%}.DisplayContainerHeight--minHeightHalf .Layer--one{padding:calc(2vh + 30px) 0}.DisplayContainerHeight--minHeightThird .Layer--one{padding:calc(2vh + 20px) 0}.DisplayContainerHeight--flex:not(.SplitLayout){-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column}.Theme-Layer-TextBlock-Container{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-flex:1;-ms-flex:1;flex:1;height:100%}.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 40px)}@media (min-width:900px){.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 50px)}}@media (min-width:1100px){.DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 60px)}}.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 100px)}@media (min-width:900px){.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 110px)}}@media (min-width:1100px){.body-editor .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight,.body-editor .Theme-TitleSection.DisplayContainerHeight--minHeight{min-height:calc(100vh - 120px)}}@media (orientation:portrait){.DeviceDetect--isiPhone .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .Theme-TitleSection.DisplayContainerHeight--minHeight .Layer--one{padding-bottom:80px}}@media (orientation:portrait) and (min-device-height:700px){.DeviceDetect--isiPhone .DeviceDetect--isEdge .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .DeviceDetect--isIE .Theme-TitleSection .DisplayContainerHeight--minHeight .Layer--one,.DeviceDetect--isiPhone .Theme-TitleSection.DisplayContainerHeight--minHeight .Layer--one{padding-bottom:120px}}.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container{-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start;-webkit-box-flex:0;-ms-flex:0 0 auto;flex:0 0 auto;height:auto}.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container .Theme-Layer-TextBlock-Inner>div:not(:empty){padding-top:20px}@media (orientation:landscape){.Theme-TitleSection.DisplayContainerHeight--flex .Theme-Layer-TextBlock-Container~.Theme-Layer-TextBlock-Container .Theme-Layer-TextBlock-Inner>div:not(:empty){min-height:80px}}@media (max-width:899px){.Theme-TextSection.Theme-Columns--2 .Theme-Column:first-child .Theme-Layer-BodyText{padding-bottom:0}.Theme-TextSection.Theme-Columns--2 .Theme-Column:last-child .Theme-Layer-BodyText{padding-top:0}.Theme-TextSection.Theme-Columns--2 .Theme-Column:last-child .Theme-Layer-BodyText--inner p:first-child{margin-top:0}}@media (max-width:619px){.Theme-TextSection.Theme-Columns--2 .Theme-Column{min-width:100%}}.Theme-BackgroundScrollmationSection{background-color:#222}@media (max-width:900px){.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{margin-top:70vh;margin-bottom:70vh}}@media (min-width:1100px){.Theme-TwoColumnScrollmationSection .Theme-Layer-BodyText{padding-top:calc(72px - 1.5rem)}}.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:40px 25px}@media (min-width:620px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:60px 25px}}@media (min-width:900px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding:72px 40px 60px}}@media (min-width:1100px){.Theme-Layer-CardCanvas,.Theme-TwoColumnScrollmationSection .media-editor-container{padding-top:110px}}.Theme-TwoColumnScrollmationCaption{padding-top:40px}@media (min-width:620px){.Theme-TwoColumnScrollmationCaption{padding-top:60px}}@media (min-width:900px){.Theme-TwoColumnScrollmationCaption{padding-top:72px}}@media (min-width:1100px){.Theme-TwoColumnScrollmationCaption{padding-top:110px}}.Theme-LinkedMediaRenderer{-webkit-transition:opacity .15s ease;transition:opacity .15s ease}.Theme-Layer-CardCanvas[data-card-canvas]{padding-top:0;padding-bottom:0;margin-top:78px;top:78px}@media (max-width:899px){.Theme-Layer-CardCanvas[data-card-canvas]{height:35vh!important;top:40px}}@media (min-width:1100px){.Theme-Layer-CardCanvas[data-card-canvas]{margin-top:76.8px;top:106.8px}}.DeviceDetect--isEdge .Theme-Layer-CardCanvas[class*=StickyPolyfillElement],.DeviceDetect--isIE .Theme-Layer-CardCanvas[class*=StickyPolyfillElement]{margin-top:0}@media (max-width:899px){.CardCanvas--tworowContainer .CardCanvas{padding:0;margin:0;-webkit-box-shadow:0 1px 1px rgba(0,0,0,.1);box-shadow:0 1px 1px rgba(0,0,0,.1);-webkit-backdrop-filter:blur(3px);backdrop-filter:blur(3px)}.Theme-Section-Light .CardCanvas--tworowContainer .CardCanvas{background-color:rgba(255,255,255,.9)}.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:calc(35vh + 10px)}}@media (max-width:899px) and (max-aspect-ratio:6/8){.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:calc(35vh + 10px)}}@media (max-width:899px){.CardCanvas--tworowContainer .CardCanvas__canvasColumn{pointer-events:none}.CardCanvas--tworowContainer .CardCanvas__canvasColumn .Theme-Caption{pointer-events:auto}.CardCanvas--tworowContainer .CardCanvasItem__caption{right:4px;bottom:4px;left:4px;max-width:initial}.CardCanvas--tworowContainer .CardCanvasItem{padding:4px;pointer-events:initial}}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:15px}@media (min-width:620px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:25px}}@media (min-width:900px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:30px}}@media (min-width:1100px){.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image{padding:40px}}.Theme-Layer-Gallery-List a,.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image .Theme-Item-Picture{display:block}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image img{max-width:100%;height:auto}.Theme-MediaSection .Theme-Layer-ResponsiveMedia-image>a{border:none}.Theme-Layer-ResponsiveMedia-embed .RichEmbed--facebook,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--instagram,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--linkedin,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--pinterest,.Theme-Layer-ResponsiveMedia-embed .RichEmbed--twitter,.Theme-Layer-responsive-media-embed .RichEmbed--facebook,.Theme-Layer-responsive-media-embed .RichEmbed--instagram,.Theme-Layer-responsive-media-embed .RichEmbed--linkedin,.Theme-Layer-responsive-media-embed .RichEmbed--pinterest,.Theme-Layer-responsive-media-embed .RichEmbed--twitter{padding:15px 0}.Theme-Layer-ResponsiveMedia-embed .twitter-tweet,.Theme-Layer-responsive-media-embed .twitter-tweet{margin:0 auto!important}.Theme-RevealSection .Theme-Layer-BodyText{width:95%;border-radius:.5em;padding-top:10px;padding-bottom:10px;margin:0 auto}@media (min-width:620px){.Theme-RevealSection .Theme-Layer-BodyText{padding-top:10px;padding-bottom:10px}}@media (min-width:1100px){.Theme-RevealSection .Theme-Layer-BodyText{padding-top:20px;padding-bottom:20px}}.Theme-RevealSection .Theme-Layer-BodyText .Theme-Overlay{border-radius:.5em}.MediaGallery{z-index:91}body:not(.body-editor) .MediaGallery{padding:15px}.body-editor .MediaGallery{margin:15px}@media (min-width:620px){body:not(.body-editor) .MediaGallery{padding:25px}.body-editor .MediaGallery{margin:25px}}@media (min-width:900px){body:not(.body-editor) .MediaGallery{padding:30px}.body-editor .MediaGallery{margin:30px}}@media (min-width:1100px){body:not(.body-editor) .MediaGallery{padding:40px}.body-editor .MediaGallery{margin:40px}.MediaGallery--Wide{margin-left:0;margin-right:0}.MediaGallery--Wide .Layout{padding-left:40px;padding-right:40px}}.MediaGallery__cell{margin:2px}@media (min-width:620px){.MediaGallery--Full .MediaGallery__cell,.MediaGallery--Narrow .MediaGallery__cell,.MediaGallery--Wide .MediaGallery__cell{margin:4px}}.MediaGallery__cell:first-child{margin-left:0}.MediaGallery__cell:last-child{margin-right:0}body:not(.body-editor) .MediaGallery__cell .Theme-BackgroundMedia{overflow:hidden}.MediaGallery__cell .Theme-Overlay{display:none}.MediaGallery--lightbox{background:rgba(34,34,34,.95)}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Lazyload{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;height:100%}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Lazyload{position:relative;overflow:hidden;margin:0 auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .FullSize{position:relative}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia img{width:auto;height:auto;max-width:100%;max-height:70vh}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia video{height:100%;margin:0 auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Videoplayer{overflow:hidden;width:auto;max-width:100%;height:100%;max-height:70vh}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Theme-Video-Wrapper,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .Theme-Video-Wrapper>div,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr__video-wrapper{height:100%}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr,.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia .plyr__video-wrapper{width:auto}.MediaGallery--lightbox .Theme-Layer-ResponsiveMedia>a{position:relative;border:1px solid #fff}.MediaGallery--lightbox .Theme-BackgroundVideo .Theme-Item-Picture{display:none}.MediaGallery--lightbox .Theme-Caption{margin-top:.25em;overflow:auto;max-width:100%;text-align:center;opacity:.6}.MediaGallery--lightbox .Theme-Caption p{color:#fff;font-size:.9em;line-height:1.3}.MediaGallery--lightbox__controls span{background-color:#fff}.Theme-MediaGallerySection.Theme-Section-Light+.Theme-MediaSection.Theme-Section-Light .Theme-Layer-ResponsiveMedia-image{padding-top:0}.Theme-MediaGallerySection.Theme-Section-Light+.Theme-MediaGallerySection.Theme-Section-Light .MediaGallery{margin-top:0}.Theme-MediaGallerySection.Theme-Section-Dark+.Theme-MediaSection.Theme-Section-Dark .Theme-Layer-ResponsiveMedia-image{padding-top:0}.Theme-MediaGallerySection.Theme-Section-Dark+.Theme-MediaGallerySection.Theme-Section-Dark .MediaGallery{margin-top:0}.GalleryRenderer--initializing{min-height:30vh}.GalleryRenderer--initializing:after{content:"";opacity:.15}.Theme-CollectionSectionSection,.Theme-SitePagesSection{overflow:hidden;min-height:auto}.body-editor:not(.body-focus-mode) .Theme-CollectionSectionSection,.body-editor:not(.body-focus-mode) .Theme-SitePagesSection{min-height:auto}.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:25px;padding-bottom:calc(25px + 45px)}@media (min-width:620px){.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:30px;padding-bottom:calc(30px + 45px)}}@media (min-width:900px){.Theme-CollectionSectionSection .Theme-Layer-Gallery:not(:empty),.Theme-SitePagesSection .Theme-Layer-Gallery:not(:empty){padding:40px;padding-bottom:calc(40px + 45px)}}.body-editor .Theme-CollectionSectionSection,.body-editor .Theme-SitePagesSection{min-height:300px}.Theme-Layer-Gallery-Heading{color:#333;margin-top:0;margin-bottom:1.5rem;font-family:"Lato",sans-serif;font-weight:700;font-size:150%;line-height:1.3;text-align:center}@media (min-width:620px){.Theme-Layer-Gallery-Heading{font-size:160%}}.Theme-Layer-Gallery-Heading:empty{display:none}.Theme-Layer-Gallery-List{margin:0 auto;padding:0;list-style:none;display:-webkit-box;display:-ms-flexbox;display:flex;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center;justify-items:center;-webkit-box-align:stretch;-ms-flex-align:stretch;align-items:stretch}.Theme-Layer-Gallery-List a:active,.Theme-Layer-Gallery-List a:focus,.Theme-Layer-Gallery-List a:hover{text-decoration:none}.Theme-Layer-Gallery-List img{display:block;width:100%;margin:0 auto}.Theme-Layer-Gallery-Item{background-color:rgba(255,255,255,.6);border:1px solid rgba(34,34,34,.2);-webkit-transition:border .15s ease;transition:border .15s ease;margin:10px;text-align:center;width:100%;max-width:400px;min-width:240px}@media (min-width:620px){.Theme-Layer-Gallery-Item{margin:15px}}.Theme-Layer-Gallery-Item:only-of-type{width:100%;max-width:800px}.Theme-Layer-Gallery-Item:active,.Theme-Layer-Gallery-Item:focus,.Theme-Layer-Gallery-Item:hover{border:1px solid rgba(34,34,34,.5);background-color:rgba(255,255,255,.8);outline:none}.Theme-Layer-Gallery-Item:focus-within{border:1px solid rgba(34,34,34,.5);background-color:rgba(255,255,255,.8);outline:2px solid}.Theme-Layer-Gallery-Item a{border:none!important;text-decoration:none;height:100%;padding:10px}@media (min-width:620px){.Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{overflow:hidden}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}@media (min-width:620px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{color:#333;margin:15px 0 10px;font-family:"Lato",sans-serif;font-weight:700;font-size:110%;line-height:1.2}@media (min-width:900px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{font-size:110%}}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description:empty,.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title:empty{margin:0}.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{color:#333;margin-top:0;margin-bottom:10px;font-family:inherit;font-weight:400;font-size:90%;line-height:1.2}@media (min-width:900px){.Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{font-size:90%}}.Theme-Collection--Default:not(:empty) .Layout{max-width:100%}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Layout{padding-left:30px;padding-right:30px}}@media (min-width:1100px){.Theme-Collection--List:not(:empty) .Layout{padding-left:40px;padding-right:40px}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Heading{margin-bottom:.5em}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-List{-webkit-box-orient:vertical;-webkit-box-direction:normal;-ms-flex-direction:column;flex-direction:column;-webkit-box-align:start;-ms-flex-align:start;align-items:flex-start}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item{text-align:left;max-width:100%;width:100%;border-top:1px solid rgba(34,34,34,.2);border-bottom:1px solid rgba(34,34,34,.2);border-left:none;border-right:none;margin:0}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:not(:first-child){border-top:none}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active,.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus,.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover{background-color:rgba(255,255,255,.8);border-top:1px solid rgba(34,34,34,.2);border-bottom:1px solid rgba(34,34,34,.2)}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active:not(:first-child),.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus:not(:first-child),.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus:not(:first-child),.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover:not(:first-child){border-top:none}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item a{display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;padding:10px}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{overflow:hidden;margin-right:10px;max-width:30%}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{margin-right:25px;max-width:25%}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{-webkit-box-flex:1;-ms-flex:1;flex:1;padding:0}@media (min-width:620px){.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{margin-top:0}.Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{margin-bottom:0}.Theme-Collection--Grid:not(:empty) .Layout{max-width:100%}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item{background-color:transparent;border:none;width:100%;text-align:center;margin:0}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item{margin:0}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:focus .Theme-Layer-Gallery-Item-Media,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:hover .Theme-Layer-Gallery-Item-Media{opacity:.3}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:focus img,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item:hover img{-webkit-transform:scale(1.05);transform:scale(1.05)}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item a{background-color:#222;display:-webkit-box;display:-ms-flexbox;display:flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;padding:10px}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item a{padding:15px}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{margin:6vh auto;padding:0}@media (min-width:620px){.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Text{padding:0}}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description,.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{color:#fff}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title{margin-top:0}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description{margin-bottom:0}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Media{position:absolute;top:0;left:0;right:0;bottom:0;opacity:.4;overflow:hidden;-webkit-transition:opacity .15s ease-in-out;transition:opacity .15s ease-in-out}.Theme-Collection--Grid:not(:empty) .Theme-Layer-Gallery-Item img{-o-object-fit:cover;object-fit:cover;height:100%;-webkit-transition:-webkit-transform .15s ease-in-out;transition:transform .15s ease-in-out;transition:transform .15s ease-in-out,-webkit-transform .15s ease-in-out}.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{width:50%}}@media (min-width:900px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item{width:25%;min-width:25%}}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Small .Theme-Layer-Gallery-Item-Text{margin:7.5vh auto}}.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item{border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item{width:50%;max-width:50%}.Theme-Collection--Grid:not(:empty).Theme-Collection--Medium .Theme-Layer-Gallery-Item-Text{margin:10vh auto}}.Theme-Collection--Grid:not(:empty).Theme-Collection--Large .Theme-Layer-Gallery-Item{max-width:100%;border:none}@media (min-width:620px){.Theme-Collection--Grid:not(:empty).Theme-Collection--Large .Theme-Layer-Gallery-Item-Text{margin:12vh auto}}.Theme-Layer-SiteGallery-Item.Theme-Layer-Gallery-Item--active,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left:before,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right:before{display:none}.Theme-Footer{z-index:100;height:60px;background:#fff;border-top:1px solid rgba(0,0,0,.1);padding:10px 15px}.Theme-Footer>.Layout{-webkit-box-align:center;-ms-flex-align:center;align-items:center;display:-webkit-box;display:-ms-flexbox;display:flex}.Theme-Footer a,.Theme-Footer a:active,.Theme-Footer a:focus,.Theme-Footer a:hover,.Theme-Footer a:visited,.Theme-Footer a:visited:active,.Theme-Footer a:visited:focus,.Theme-Footer a:visited:hover{border-bottom:none}.Theme-Footer .Layout__snap--xright{padding:0}@media (max-width:620px){.Theme-Footer .Layout__snap--xright{width:auto;right:auto;left:0}}.Theme-Footer .Theme-FooterTopLink{width:60px;height:40px;font-size:11px;text-transform:uppercase;color:#333;text-decoration:none;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Oxygen-Sans,Ubuntu,Cantarell,"Helvetica Neue",sans-serif}@media (max-width:620px){.Theme-Footer .Theme-FooterTopLink{left:auto;top:auto;display:block;-webkit-transform:initial;transform:initial;right:0}}.Theme-Footer .Theme-FooterTopLink:before{border-style:solid;border-width:1px 1px 0 0;content:"";display:block;height:16px;left:50%;position:relative;top:8px;margin-bottom:4px;-webkit-transform:rotate(-45deg);transform:rotate(-45deg);width:16px;margin-left:-8px}.Theme-Footer .Theme-FooterTopLink:hover{color:#333;opacity:.65;text-decoration:none}.Theme-Footer .Theme-CreatedWithShorthand{display:block;height:40px;margin-top:-1px;width:auto;max-width:none}@media (min-width:620px){.Theme-Footer .Theme-CreatedWithShorthand{float:right}}.Theme-Footer .Theme-FooterLogo--container{display:-webkit-inline-box;display:-ms-inline-flexbox;display:inline-flex;-webkit-box-align:center;-ms-flex-align:center;align-items:center;font-size:14px;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Oxygen-Sans,Ubuntu,Cantarell,"Helvetica Neue",sans-serif;text-decoration:none;color:#222;-webkit-transition:opacity .15s ease-in-out;transition:opacity .15s ease-in-out}.Theme-Footer .Theme-FooterLogo--container:active,.Theme-Footer .Theme-FooterLogo--container:hover{opacity:.9}.Theme-Footer .Theme-FooterLogo{width:35px;margin-right:7px;font-size:0}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxsmall{font-size:calc(1em + 1vmin);line-height:1.2}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxsmall{font-size:calc(1em + 2vmin);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xsmall{font-size:calc(1em + 3.5vmin);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-small{font-size:calc(1em + 5vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-normal{font-size:calc(1em + 6.5vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-large{font-size:calc(1em + 8vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xlarge{font-size:calc(1em + 10vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxlarge{font-size:calc(1em + 12vmin);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxlarge{font-size:calc(1em + 13vmin);line-height:1}@media (max-width:620px),(orientation:landscape) and (max-width:900px){.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxsmall{font-size:1em;line-height:1.4}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxsmall{font-size:calc(1em*1.25);line-height:1.3}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xsmall{font-size:calc(1em*1.5);line-height:1.2}.Theme-Layer-TextBlock-Inner .Theme-TextSize-small{font-size:calc(1em*1.75);line-height:1.1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-normal{font-size:calc(1em*2);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-large{font-size:calc(1em*2.5);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xlarge{font-size:calc(1em*3);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxlarge{font-size:calc(1em*3.6);line-height:1}.Theme-Layer-TextBlock-Inner .Theme-TextSize-xxxlarge{font-size:calc(1em*4.75);line-height:1}}@media (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{width:100%;margin:0}}@media (min-width:620px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:450px}}@media (min-width:900px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:525px}}@media (min-width:1100px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:620px}}@media (min-width:1400px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:680px}}@media (min-width:1750px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:780px}}@media (min-width:2000px) and (orientation:landscape){.Theme-Section-Layout--Half .Theme-Layer-TextBlock-Inner{max-width:880px}}.Theme-Section-Light,.Theme-Section-Light.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText,.Theme-Section-Light.Theme-BackgroundScrollmationSection .Theme-Overlay,.Theme-Section-Light.Theme-RevealSection .Theme-Overlay,.Theme-Section-Light.Theme-TextOverMediaSection .Theme-Overlay,.Theme-Section-Light.Theme-TitleSection .Theme-Overlay{background-color:#fff}.Theme-Section-Dark{background-color:#222;color:#fff}.Theme-Section-Dark.Theme-TextOverMediaSection .Theme-Overlay,.Theme-Section-Dark.Theme-TitleSection .Theme-Overlay{background-color:#000}.Theme-Section-Dark .Theme-Layer-BodyText p,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-Large,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-Small,.Theme-Section-Dark .Theme-Layer-BodyText-Heading-xs,.Theme-Section-Dark .Theme-Layer-BodyText-List-Alpha,.Theme-Section-Dark .Theme-Layer-BodyText-List-Ordered,.Theme-Section-Dark .Theme-Layer-BodyText-List-Roman,.Theme-Section-Dark .Theme-Layer-BodyText-List-Unordered{color:#fff}.Theme-Section-Dark .Theme-Caption p,.Theme-Section-Dark .Theme-Layer-BodyText-Blockquote,.Theme-Section-Dark .Theme-Layer-BodyText-QuoteCite{color:rgba(255,255,255,.7)}.Theme-Section-Dark div:not(.Block-Active)>.Theme-Layer-BodyText-Dropcap:first-letter{color:inherit}.Theme-Section-Dark .Theme-Layer-BodyText-Breakout{background:rgba(34,34,34,.2);border-color:#fff}.Theme-Section-Dark .Theme-Layer-BodyText-Indent{border-left-color:rgba(255,255,255,.1)}.Theme-Section-Dark .Theme-Layer-BodyText-Button{color:#fff}.Theme-Section-Dark .Theme-Layer-BodyText-Button:not([class*=Theme-BackgroundColor]){background:#00a7cf}.body-editor .Theme-Section-Dark .Theme-Layer-BodyText-Button{color:#fff!important}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight{background-color:rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight:hover{background-color:rgba(255,255,255,.4)}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight:focus{background-color:rgba(255,255,255,.4);outline:#fff auto 1px}.Theme-Section-Dark .Theme-Layer-BodyText-Highlight .Theme-Layer-BodyText-Highlight--Icon{background-color:#fff}.Theme-Section-Dark .Theme-Layer-TextBlock-Inner,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a{color:#fff}.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:active,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:focus,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:hover{color:#fff}.Theme-Section-Dark .Theme-Layer-Gallery-Heading,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner .Theme-Title,.Theme-Section-Dark .Theme-Layer-TextBlock-Inner a:visited{color:#fff}.Theme-Section-Dark .Theme-Layer-Gallery-Item{background-color:rgba(34,34,34,.6);border:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Layer-Gallery-Item:active,.Theme-Section-Dark .Theme-Layer-Gallery-Item:focus,.Theme-Section-Dark .Theme-Layer-Gallery-Item:hover{border:1px solid rgba(255,255,255,.5);background-color:rgba(34,34,34,.8)}.Theme-Section-Dark .Theme-Layer-Gallery-Item-Description,.Theme-Section-Dark .Theme-Layer-Gallery-Item-Title{color:#fff}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item{background-color:rgba(34,34,34,.6);border-top:1px solid rgba(255,255,255,.2);border-bottom:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:not(:first-child){border-top:none}.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:active,.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:focus,.Theme-Section-Dark .Theme-Collection--List:not(:empty) .Theme-Layer-Gallery-Item:hover{background-color:rgba(34,34,34,.8);border-top:1px solid rgba(255,255,255,.2);border-bottom:1px solid rgba(255,255,255,.2)}.Theme-Section-Dark.Theme-RevealSection .Theme-Overlay{background-color:#222}@media (max-width:899px){.Theme-Section-Dark .CardCanvas--tworowContainer .CardCanvas{background-color:rgba(34,34,34,.9)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{background:rgba(0,0,0,.7)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Overlay{background-color:#000}}@media (min-width:900px){.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Center .Theme-Layer-BodyText{background:rgba(0,0,0,.7)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Center .Theme-Overlay{background-color:#000}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Layer-BodyText{height:100%}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left:before{content:"";display:block;width:70%;max-width:1500px;z-index:91;position:absolute;top:0;left:0;bottom:0;background:-webkit-gradient(linear,right top,left top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.65)),color-stop(60%,rgba(0,0,0,.8)));background:linear-gradient(270deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.65) 30%,rgba(0,0,0,.8) 60%)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Overlay{height:auto;right:auto;width:140%;left:0;background:-webkit-gradient(linear,right top,left top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.8)),color-stop(60%,#000));background:linear-gradient(270deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.8) 30%,#000 60%);-webkit-box-shadow:-700px 0 0 #000;box-shadow:-700px 0 0 #000}.body-editor .Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Left .Theme-Overlay{top:-2px;bottom:-2px;-webkit-box-shadow:-440px 0 0 #000;box-shadow:-440px 0 0 #000}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Layer-BodyText{height:100%}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right:before{content:"";display:block;width:70%;max-width:1500px;z-index:91;position:absolute;top:0;right:0;left:auto;bottom:0;background:-webkit-gradient(linear,left top,right top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.65)),color-stop(60%,rgba(0,0,0,.8)));background:linear-gradient(90deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.65) 30%,rgba(0,0,0,.8) 60%)}.Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Overlay{height:auto;left:auto;width:140%;right:0;background:-webkit-gradient(linear,left top,right top,color-stop(0,rgba(0,0,0,0)),color-stop(1%,rgba(0,0,0,0)),color-stop(30%,rgba(0,0,0,.8)),color-stop(60%,#000));background:linear-gradient(90deg,rgba(0,0,0,0) 0,rgba(0,0,0,0) 1%,rgba(0,0,0,.8) 30%,#000 60%);-webkit-box-shadow:700px 0 0 #000;box-shadow:700px 0 0 #000}.body-editor .Theme-Section-Dark.Theme-BackgroundScrollmationSection.Theme-BodyTextColumn-Right .Theme-Overlay{top:-2px;bottom:-2px;-webkit-box-shadow:440px 0 0 #000;box-shadow:440px 0 0 #000}}.Theme-Section-Custom:not([class*=Theme-BackgroundColor]):not(.Theme-NavigationBar){background-color:#fff}.Theme-Section-HasOverlay .Theme-Layer-BodyText{background-color:transparent!important}.Theme-CustomHtmlSection,.Theme-Section-HasOverlay.Theme-Section-Dark.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{background-color:transparent}.Theme-Section[class*=Theme-ForegroundColor] .Theme-Caption p,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Blockquote,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Dropcap,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-Large,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-Small,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-Heading-xs,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Alpha,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Ordered,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Roman,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-List-Unordered,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-BodyText-QuoteCite,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Heading,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Description,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item .Theme-Layer-Gallery-Item-Title,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-Gallery-Item a,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Byline,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-LeadIn,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-StoryTitle,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-SubTitle,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Text,.Theme-Section[class*=Theme-ForegroundColor] .Theme-Layer-TextBlock-Inner .Theme-Title{color:inherit}.Theme-Section a span[class*=Theme-ForegroundColor],.Theme-Section a:visited span[class*=Theme-ForegroundColor]{border-bottom:1px dotted}.Theme-Section a:active span[class*=Theme-ForegroundColor],.Theme-Section a:focus span[class*=Theme-ForegroundColor],.Theme-Section a:hover span[class*=Theme-ForegroundColor],.Theme-Section a:visited:active span[class*=Theme-ForegroundColor],.Theme-Section a:visited:focus span[class*=Theme-ForegroundColor],.Theme-Section a:visited:hover span[class*=Theme-ForegroundColor]{border-bottom:1px solid}.h-align-left{text-align:left!important}.h-align-left.InlineElement{-webkit-box-pack:start;-ms-flex-pack:start;justify-content:flex-start}.h-align-center{text-align:center!important}.h-align-center.InlineElement{-webkit-box-pack:center;-ms-flex-pack:center;justify-content:center}.h-align-right{text-align:right!important}.h-align-right.InlineElement{-webkit-box-pack:end;-ms-flex-pack:end;justify-content:flex-end}@media (min-width:900px){.Theme-BodyTextColumn-Left .Theme-Layer-BackgroundCanvas .Theme-Lazyload-Spinner{left:75%}.Theme-BodyTextColumn-Right .Theme-Layer-BackgroundCanvas .Theme-Lazyload-Spinner{left:25%}}@-webkit-keyframes loading-spinner{0%{-webkit-transform:rotate(0deg);transform:rotate(0deg)}to{-webkit-transform:rotate(360deg);transform:rotate(360deg)}}@keyframes loading-spinner{0%{-webkit-transform:rotate(0deg);transform:rotate(0deg)}to{-webkit-transform:rotate(360deg);transform:rotate(360deg)}}.custom-ad{text-align:center;padding:15px 0;background-color:rgba(0,0,0,.035)}.custom-ad div{margin:0 auto}.custom-ad .custom-ad-label{font-size:11px;text-transform:uppercase;color:rgba(80,80,80,.5);margin-bottom:5px;margin-top:-8px}hr{border:none;border-bottom:2px solid rgba(204,204,204,.3)}.Core--rootElement .oo-player-container *{position:initial}.sh-text-xs{font-size:12px}.sh-text-sm{font-size:14px}.sh-text-md{font-size:80%}.sh-text-lg{font-size:120%}.sh-text-xl{font-size:150%}[dir=rtl] .Theme-SocialIcons{right:auto;margin-right:0;left:0;margin-left:15px}@media (max-width:1099px){[dir=rtl] .Theme-Hamburger~.Theme-SocialIcons{left:45px;left:calc(45px + env(safe-area-inset-left))}}[dir=rtl] .Theme-Hamburger{right:auto;left:15px;left:calc(15px + env(safe-area-inset-left))}@media (max-width:1099px){[dir=rtl] .Theme-NavigationBar{right:auto!important;left:-110%!important;-webkit-transition:left .15s ease-in-out;transition:left .15s ease-in-out}[dir=rtl] .Navigation--isActive{right:auto!important;left:0!important}}.body-editor .MediaRenderer__textBlocksInner:first-child>div{padding-top:0;top:-20vh}.body-editor .Theme-Layer-BodyText--inner h2,.body-editor .Theme-Layer-BodyText--inner h3,.body-editor .Theme-Layer-BodyText--inner h4,.body-editor .Theme-Layer-BodyText--inner p{min-height:1.7em}.body-editor .RichEmbed--typeform{pointer-events:none}.body-editor .Theme-Layer-responsive-media-embed .Theme-Caption p{text-align:left}.InstantImage__img{-webkit-filter:blur(15px);filter:blur(15px)}.Theme-Layer-BodyText-Dropcap:after{content:"";clear:both;display:table}body{overflow:initial}.Theme-HeaderContainer b,.Theme-HeaderContainer strong,.Theme-Story b,.Theme-Story strong{font-weight:700}.Theme-HeaderContainer p:empty,.Theme-Story p:empty{padding:0;margin:0}.Theme-Layer-BodyText{word-wrap:break-word}.Layout,.Theme-Caption,.Theme-Column{padding-left:0;padding-right:0}@media (min-width:1100px) and (max-width:1399px){.Layout:not(.Theme-Header){max-width:1240px}}.Layout__row{margin:0}.Theme-Layer-TextBlock{pointer-events:none}.BlockHTML iframe,.InlineHTML iframe{border:none;max-width:100%}.BlockHTML .instagram-media,.InlineHTML .instagram-media{margin:0 auto!important}.InlineHTML img{max-width:100%;max-height:100%}.body-editor .Theme-HeaderContainer,.body-editor .Theme-Story{opacity:1}.DeviceDetect--isIE .FullSize--fixedChild{z-index:auto}.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:40px}@media (min-width:620px){.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:50px}}@media (min-width:900px){.StickyPolyfillElement--stick:not(.Theme-HeaderContainer--hidden)+.Theme-Story,.StickyPolyfillElement--top:not(.Theme-HeaderContainer--hidden)+.Theme-Story{top:60px}}.Theme-360Video-Link,.video_360_ios_link{overflow:hidden;display:block}.Theme-360Video-Button,.video-btn{position:absolute;display:inline-block;width:225px;top:50%;z-index:1;left:50%;background:rgba(0,0,0,.6) url(data:image/png;base64,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) 12px 12px no-repeat;background-size:20px auto;padding:12px 0 12px 38px;letter-spacing:0;border-radius:4px;text-transform:uppercase;font-weight:700;color:#fff;-webkit-transform:translate(-50%,-50%);transform:translate(-50%,-50%);text-align:left;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Helvetica,Arial,sans-serif,"Apple Color Emoji","Segoe UI Emoji","Segoe UI Symbol";font-size:14px;line-height:1;-webkit-box-shadow:0 0 0 1000px rgba(0,0,0,.1);box-shadow:0 0 0 1000px rgba(0,0,0,.1)}.twitter-tweet{margin:0 auto}@media (min-width:900px){.Theme-Layer-BodyText-List-Ordered+.Core--md-srOnly+.Theme-Layer-BodyText-List-Ordered,.Theme-Layer-BodyText-List-Unordered+.Core--md-srOnly+.Theme-Layer-BodyText-List-Unordered{margin-top:-.75rem}html:not(.DeviceDetect--isEdge):not(.DeviceDetect--isIE) .CardCanvasItem__image img{max-width:750px;max-height:75vh!important}}.DeviceDetect--isIE .Theme-Layer-BodyText .InlineMedia--image .Lazyload__loading,.DeviceDetect--isIE .Theme-TextOverMediaSection .InlineMedia--image .Lazyload__loading,.DeviceDetect--isIE .Theme-TitleSection .InlineMedia--image .Lazyload__loading,.nav-item-promo~.nav-item-promo,.shorthand_story-template-default:before,figure[class*=h-align-] .Theme-Lazyload-Spinner,figure[class*=media-size-] .Theme-Lazyload-Spinner{display:none}.Videoplayer--responsive{background-color:#000}.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 40px);top:50%;-webkit-transform:translateY(-50%);transform:translateY(-50%)}@media (min-width:620px){.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 50px)}}@media (min-width:1100px){.Videoplayer--responsive embed,.Videoplayer--responsive iframe,.Videoplayer--responsive object{max-height:calc(100vh - 94px)}}.CardCanvasItem>a:after,.Theme-Layer-BodyText .InlineMedia--image>a:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:after,.Theme-Layer-ResponsiveMedia-image>a:after{content:"";position:absolute;background:rgba(0,0,0,.35) url(data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAADYAAAA2CAMAAAC7m5rvAAAADFBMVEX////////////////1pQ5zAAAABHRSTlMB/I1CoQ5N8QAAAM5JREFUeNrN1kEKwzAQQ9Fauv+duzCJalwy83EX1c7gZ0LGEXn9IpaNzZgRUhp33FfjM2Iqjqk4pCTglq1tp2wEztlG3L6pMz9Hbe6BKWpzqpi/Pzliceghw9x4JTnHF+sPYC5cMsfNVaLW5doZu8oZN3FRwDmL9FnvQ90P0aNbo7rPRhkduKJggfM6B9Bnts/7jDuPxKTPEqE+C8N9lvNZn+lScfrDPktYnyWozxLYZzPmfbaOGzif9ZnZj0cUcFGtMJUwlYgpMuWiz07zBirwBIVbSDEiAAAAAElFTkSuQmCC) 6px center no-repeat;background-size:18px auto;color:transparent;border-radius:5px;top:5px;right:5px;z-index:1;width:30px;height:30px;line-height:30px;overflow:hidden;font-size:11px;text-align:left;text-transform:uppercase;font-weight:700;font-family:-apple-system,BlinkMacSystemFont,"Segoe UI",Roboto,Helvetica,Arial,sans-serif,"Apple Color Emoji","Segoe UI Emoji","Segoe UI Symbol";-webkit-transition:width .15s ease,color .15s ease .15s;transition:width .15s ease,color .15s ease .15s}@media (hover:none) and (pointer:coarse){.CardCanvasItem>a:after,.Theme-Layer-BodyText .InlineMedia--image>a:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:after,.Theme-Layer-ResponsiveMedia-image>a:after{content:"Visit link";color:#fff;width:96px;padding-left:29px;background-color:rgba(0,0,0,.75)}}.CardCanvasItem>a:hover:after,.Theme-Layer-BodyText .InlineMedia--image>a:hover:after,.Theme-Layer-BodyText .InlineMedia--image__inner a:hover:after,.Theme-Layer-ResponsiveMedia-image>a:hover:after{content:"Visit link";color:#fff;width:96px;padding-left:29px;background-color:rgba(0,0,0,.75)}.DeviceDetect--isIE .Theme-Layer-BodyText .InlineMedia--image .FullSize,.DeviceDetect--isIE .Theme-TextOverMediaSection .InlineMedia--image .FullSize,.DeviceDetect--isIE .Theme-TitleSection .InlineMedia--image .FullSize{position:relative;top:auto;left:auto}@media (min-width:900px){.DisplayContainerHeight--flex.Display--md-block{display:-webkit-box!important;display:-ms-flexbox!important;display:flex!important}}[dir=rtl]{direction:rtl}.Theme-TextOverMediaSection .InlineMedia .Lazyload__loading,.Theme-TitleSection .InlineMedia .Lazyload__loading{opacity:0!important}body:not(.body-editor) .Theme-Layer-BodyText-QuoteCite:empty{display:none}.Theme-Section-Layout--Full .Theme-BackgroundImage .FullSize--fixedChild{clip-path:none;-webkit-clip-path:none}#td-outer-wrap,.shorthand_story-template-default .overflow-container{overflow:initial}@media (max-width:960px){.shorthand_story-template-default #main-sidebar{padding:1.5em}.shorthand_story-template-default #main{padding:0}}.shorthand-embed-article,.shorthand-embed-body,.shorthandLoader-Container{min-height:100vh!important}.shorthand-embed-article .FullSize,.shorthand-embed-article .FullSize--basic{height:100%}.shorthand-embed-article .Theme-Overlay.FullSize{min-height:100%}.shorthand-embed-article .Theme-Section{width:100%}.shorthand-embed-article .Theme-Section:not(.Theme-TitleSection) .DisplayContainerHeight:not(.DisplayContainerHeight--flex){height:100vh}.shorthand-embed-body article{overflow:initial!important;padding:0}.shorthand-embed-body .Theme-Navigation-ItemList:empty{display:none}@media print{body,html{height:auto}abbr[title]:after{content:" (" attr(title) ")"}blockquote,pre,tr{page-break-inside:avoid}thead{display:table-header-group}h2,h3,p{orphans:3;widows:3}.Theme-Layer-BodyText a[href^="#"]:after,.Theme-Layer-BodyText a[href^="javascript:"]:after{content:""}.Theme-Layer-BodyText a[href]:after{content:" (" attr(href) ")"}.Theme-Section.DisplayContainerHeight,.Theme-Section.DisplayContainerHeight--minHeight{height:0!important;min-height:0!important;padding-top:52.65%}.FullSize--fullHeight,.Theme-Item-MediaRenderer aside,.Theme-Item-MediaRenderer img{display:block;height:100%;position:absolute;top:0;left:0;right:0;bottom:0}.DisplayContainerHeight{height:100%}.DisplayContainerHeight--minHeight{min-height:100%}.FullSize--fixedChild .FullSize__fixedChild{position:absolute;-o-object-fit:cover;object-fit:cover;top:0;left:0;right:0;bottom:0}.Theme-Story .PositionSticky{position:relative!important}.CardCanvas--tworowContainer .CardCanvas__canvasColumn{display:none}.CardCanvas--tworowContainer .CardCanvas__textColumn{padding-top:2em}.MediaRenderer__fixedCaption{position:absolute}.Theme-Item-MediaRenderer{height:100%!important;position:absolute;top:0;left:0;right:0;bottom:0}.Theme-Item-MediaRenderer aside,.Theme-Item-MediaRenderer img{width:100%}.Theme-Footer,.Theme-RevealSection{display:none}.Theme-BackgroundScrollmationSection.DisplayContainerHeight,.Theme-BackgroundScrollmationSection.DisplayContainerHeight--minHeight{height:auto!important;min-height:auto!important;padding-top:0}.Theme-BackgroundScrollmationSection .Theme-Layer-BodyText{margin-top:0!important;margin-bottom:0!important}.Lazyload__loading{display:none!important}.Theme-Item-Picture,[data-lazyload-item]{position:relative!important;height:auto!important;top:auto!important;left:auto!important}.BackgroundScrollmationItem img,[data-lazyload-item] img{opacity:1!important}.BackgroundScrollmation{height:auto!important}.BackgroundScrollmationItem{width:100%!important;display:block!important;opacity:1!important;bottom:auto!important;right:auto!important}.BackgroundScrollmationItem,.BackgroundScrollmationItem .FullSize{position:relative!important;height:auto!important;top:auto!important}.Theme-Layer-BodyText .InlineMedia img{max-width:50%}.Theme-FooterTopLink,.Theme-HeaderContainer{display:none!important}}.Theme-ForegroundColor-0{color:#19af90}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-0,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-0,.text-edit-dropdown-colour.Theme-BackgroundColor-0,.text-edit-dropdown-colour.Theme-ForegroundColor-0{background:#19af90}.Theme-BackgroundColor-0{background-color:#19af90}.Theme-ForegroundColor-1{color:#00a7cf}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-1,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-1,.text-edit-dropdown-colour.Theme-BackgroundColor-1,.text-edit-dropdown-colour.Theme-ForegroundColor-1{background:#00a7cf}.Theme-BackgroundColor-1{background-color:#00a7cf}.Theme-ForegroundColor-2{color:#f2744d}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-2,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-2,.text-edit-dropdown-colour.Theme-BackgroundColor-2,.text-edit-dropdown-colour.Theme-ForegroundColor-2{background:#f2744d}.Theme-BackgroundColor-2{background-color:#f2744d}.Theme-ForegroundColor-3{color:#ccb87e}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-3,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-3,.text-edit-dropdown-colour.Theme-BackgroundColor-3,.text-edit-dropdown-colour.Theme-ForegroundColor-3{background:#ccb87e}.Theme-BackgroundColor-3{background-color:#ccb87e}.Theme-ForegroundColor-4{color:#aaa}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-4,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-4,.text-edit-dropdown-colour.Theme-BackgroundColor-4,.text-edit-dropdown-colour.Theme-ForegroundColor-4{background:#aaa}.Theme-BackgroundColor-4{background-color:#aaa}.Theme-ForegroundColor-5{color:#777}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-5,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-5,.text-edit-dropdown-colour.Theme-BackgroundColor-5,.text-edit-dropdown-colour.Theme-ForegroundColor-5{background:#777}.Theme-BackgroundColor-5{background-color:#777}.Theme-ForegroundColor-6{color:#424242}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-6,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-6,.text-edit-dropdown-colour.Theme-BackgroundColor-6,.text-edit-dropdown-colour.Theme-ForegroundColor-6{background:#424242}.Theme-BackgroundColor-6{background-color:#424242}.Theme-ForegroundColor-7{color:#ec3f3f}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-7,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-7,.text-edit-dropdown-colour.Theme-BackgroundColor-7,.text-edit-dropdown-colour.Theme-ForegroundColor-7{background:#ec3f3f}.Theme-BackgroundColor-7{background-color:#ec3f3f}.Theme-ForegroundColor-8{color:#8ac064}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-8,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-8,.text-edit-dropdown-colour.Theme-BackgroundColor-8,.text-edit-dropdown-colour.Theme-ForegroundColor-8{background:#8ac064}.Theme-BackgroundColor-8{background-color:#8ac064}.Theme-ForegroundColor-9{color:#fff}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-9,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-9,.text-edit-dropdown-colour.Theme-BackgroundColor-9,.text-edit-dropdown-colour.Theme-ForegroundColor-9{background:#fff}.Theme-BackgroundColor-9{background-color:#fff}.Theme-ForegroundColor-10{color:#000}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-10,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-10,.text-edit-dropdown-colour.Theme-BackgroundColor-10,.text-edit-dropdown-colour.Theme-ForegroundColor-10{background:#000}.Theme-BackgroundColor-10{background-color:#000}.Theme-ForegroundColor-11{color:#93d6c7}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-11,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-11,.text-edit-dropdown-colour.Theme-BackgroundColor-11,.text-edit-dropdown-colour.Theme-ForegroundColor-11{background:#93d6c7}.Theme-BackgroundColor-11{background-color:#93d6c7}.Theme-ForegroundColor-12{color:#8cd3e6}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-12,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-12,.text-edit-dropdown-colour.Theme-BackgroundColor-12,.text-edit-dropdown-colour.Theme-ForegroundColor-12{background:#8cd3e6}.Theme-BackgroundColor-12{background-color:#8cd3e6}.Theme-ForegroundColor-13{color:#f7b9a9}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-13,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-13,.text-edit-dropdown-colour.Theme-BackgroundColor-13,.text-edit-dropdown-colour.Theme-ForegroundColor-13{background:#f7b9a9}.Theme-BackgroundColor-13{background-color:#f7b9a9}.Theme-ForegroundColor-14{color:#e5dbc0}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-14,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-14,.text-edit-dropdown-colour.Theme-BackgroundColor-14,.text-edit-dropdown-colour.Theme-ForegroundColor-14{background:#e5dbc0}.Theme-BackgroundColor-14{background-color:#e5dbc0}.Theme-ForegroundColor-15{color:#f4a0a1}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-15,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-15,.text-edit-dropdown-colour.Theme-BackgroundColor-15,.text-edit-dropdown-colour.Theme-ForegroundColor-15{background:#f4a0a1}.Theme-BackgroundColor-15{background-color:#f4a0a1}.Theme-ForegroundColor-16{color:#c5dfb4}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-16,.text-edit-colour-value .text-edit-colour-swatch.Theme-ForegroundColor-16,.text-edit-dropdown-colour.Theme-BackgroundColor-16,.text-edit-dropdown-colour.Theme-ForegroundColor-16{background:#c5dfb4}.Theme-BackgroundColor-16{background-color:#c5dfb4}.Theme-BackgroundColor-17{background-color:transparent}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-17,.text-edit-dropdown-colour.Theme-BackgroundColor-17{background:0 0} /*-->*/ " + "ipt>"); } })(navigator, 'userAgent', 'appVersion', 'script', document); //--> TwitterFacebook Inflatable, shape-changing spinal implants could help treat severe pain

Lower Back Pain. Credit: David Cross (CC BY-NC-SA 2.0)

Lower Back Pain. Credit: David Cross (CC BY-NC-SA 2.0)

A team of engineers and clinicians has developed an ultra-thin, inflatable device that can be used to treat the most severe forms of pain without the need for invasive surgery.

 The device, developed by researchers at the University of Cambridge, uses a combination of soft robotic fabrication techniques, ultra-thin electronics and microfluidics.

 The device is so thin – about the width of a human hair – that it can be rolled up into a tiny cylinder, inserted into a needle, and implanted into the epidural space of the spinal column, the same area where injections are administered to control pain during childbirth.

Once correctly positioned, the device is inflated with water or air so that it unrolls like a tiny air mattress, covering a large section of the spinal cord. When connected to a pulse generator, the ultra-thin electrodes start sending small electrical currents to the spinal cord, which disrupt pain signals.

 Early tests of the device suggest that it could be an effective treatment for many forms of severe pain – including leg and back pain – which are not remedied by painkillers. It could also be adapted into a potential treatment for paralysis or Parkinson’s disease. However, extensive tests and clinical trials will be required before the device can be used on patients.

 Although other types of spinal cord stimulation devices are currently used to treat severe pain, the most effective of these devices are bulky and require invasive surgery, while current keyhole devices are far less effective at treating pain. By combining the clinical effectiveness of the surgical devices and the ease of implantation of the keyhole devices, the Cambridge-developed device could be an effective, long-term solution to intractable pain, which affects millions worldwide. The results are reported in the journal Science Advances.

Pain is something that everyone experiences, and for the vast majority of people, it is temporary and treatable. However, for some, pain becomes debilitating. In the UK, back pain is the leading cause of disability, costing the economy around £12 billion per year. In the US, the Centers for Disease Control and Prevention estimates that as many as one in 12 Americans suffer from intractable back pain, which does not respond to conventional treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) or opioids.

Spinal cord stimulation (SCS) is an option for those who suffer from intractable back pain or other types of neuropathic pain, but despite its effectiveness, its use is limited, with just 50,000 procedures carried out worldwide each year.

“Spinal cord stimulation is a treatment of last resort, for those whose pain has become so severe that it prevents them from carrying out everyday activities,” said Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences, one of the paper’s senior authors. “However, the two main types of SCS devices both have flaws, which may be one reason their use is limited, even though millions struggle with chronic pain every day.”

The most effective SCS device in clinical use is a paddle-type device, which covers a wide area of the spinal cord but is bulky and requires invasive surgery under general anaesthetic. The other type of device can be implanted with a needle and only requires local anaesthetic, but it covers a smaller area and is less clinically effective than a paddle-type device.

“Our goal was to make something that’s the best of both worlds – a device that’s clinically effective but that doesn’t require complex and risky surgery,” said Dr Christopher Proctor from Cambridge’s Department of Engineering, the paper’s other senior author. “This could help bring this life-changing treatment option to many more people.”

“In order to end up with something that can be implanted with a needle, we needed to make the device as thin as possible,” said co-first author Ben Woodington, also from the Department of Engineering.

The researchers used a combination of manufacturing techniques to build their device: flexible electronics used in the semiconductor industry; tiny microfluidic channels used in drug delivery; and shape-changing materials used in soft robotics.

Their finished device is just 60 microns thick – thin enough that it can be rolled up and placed in a needle for implantation. However, after implantation, the device expands out to cover a wide area of the spinal cord, thanks to the microfluidic channels.

“Thin-film electronics aren’t new, but incorporating fluid chambers is what makes our device unique – this allows it to be inflated into a paddle-type shape once it is inside the patient,” said Proctor.  

“Our earlier versions were actually so thin that they were invisible to x-rays, which the surgeon would need to use to confirm they’re in the right place before inflating the device,” said Woodington. “We added some bismuth particles to make it visible without increasing the thickness too much. Designing a device is one thing, but putting it into surgical use is quite another.”

Your browser does not support this video

The researchers validated their device in vitro and on a human cadaver model. They are currently working with a manufacturing partner to further develop and scale up their device and are hoping to begin tests in patients within two to three years.

“The way we make the device means that we can also incorporate additional components – we could add more electrodes or make it bigger in order to cover larger areas of the spine with increased accuracy,” said Barone. “This adaptability could make our SCS device a potential treatment for paralysis following spinal cord injury or stroke or movement disorders such as Parkinson’s disease. An effective device that doesn’t require invasive surgery could bring relief to so many people.”

“This technology has the potential to transform clinical treatment, significantly improve pain management for so many people, and reach patients who cannot be treated with existing devices,” said Dr Rachel Atfield, Commercialisation Manager at Cambridge Enterprise, the University’s commercialisation company, which has patented the device.

The research was supported in part by the Engineering and Physical Sciences Research Council, the Borysiewicz Biomedical Science Fellowship, the Medical Research Council, Health Education England and the National Institute for Health Research.

Reference:
Ben J. Woodington et al. ‘Electronics with Shape Actuation for Minimally Invasive Spinal Cord Stimulation.’ Science Advances (2021). DOI: 10.1126/sciadv.abg7833

TopBuilt with Shorthand Summary: 

A team of engineers and clinicians has developed an ultra-thin, inflatable device that can be used to treat the most severe forms of pain without the need for invasive surgery.

Image: Affiliation (schools and institutions): Department of EngineeringDepartment of Clinical NeurosciencesSchool of TechnologySchool of Clinical MedicineCambridge EnterprisePeople (our academics and staff): Damiano BaroneChristopher ProctorBen WoodingtonSubject (including Spotlight on ... where applicable): Neurosciencebrainpaintechnology transfercommercialisationmedical deviceback painroboticsStoriesSection: Research

Trinity Challenge announces inaugural winners

Fri, 25/06/2021 - 15:43

The eight winners have been selected by an international panel of expert judges, out of a total of 340 applications from 61 countries. The competition has seen unprecedented collaborations between the private, public, charitable and academic sectors, and will drive a step-change in using data and analytics for pandemic preparedness.

The University of Cambridge joined a coalition of some of the world’s leading businesses and academic and tech institutions to launch The Trinity Challenge in September 2020. The global challenge, convened by Dame Sally Davies, Master of Trinity College, provides a £10m prize fund for breakthrough solutions to make sure one billion more people are better protected against health emergencies.

Participatory One Health Disease Detection (PODD), which empowers farmers to identify and report zoonotic diseases that could potentially pass from animals to humans, has been named the grand prize winner at the inaugural awards ceremony. The organisation is being awarded £1.3 million (US$1.8 million) in pledged funding.

Led by Susumpat Patipow, General Director at OpenDream, PODD has developed a platform for livestock owners to report suspected animal illness, and in return receive veterinary care to improve animal health. If it appears a disease outbreak is likely, local health officials will quarantine the sick animals, saving the remaining livestock and possibly preventing the next COVID-19-type outbreak.

Having already achieved significant success in Thailand, with a network of 20,000 farmers helping to detect and control disease outbreaks, PODD is looking to expand its operations to Cambodia, India, Indonesia, Laos, Uganda and Vietnam over the next three years.

BloodCounts! - an international consortium of scientists, led by Professor Carola-Bibiane Schönlieb from Cambridge’s Department of Applied Mathematics and Theoretical Physics (DAMTP) that has developed an innovative infectious disease outbreak detection system, was one of two second-prize winners, each awarded £1 million in pledged funding.

Developed by Dr Michael Roberts and Dr Nicholas Gleadall, the BloodCounts! Solution uses data from routine blood tests and powerful AI-based techniques to provide a ‘tsunami-like’ early warning system for new disease outbreaks.

“Since the beginning of the pandemic I have been developing AI-based methods to aid in medical decision making for COVID-19 patients, starting with analysis of Chest X-ray data,” said Roberts, who is affiliated with DAMTP and the Cambridge Mathematics of Information in Healthcare (CMIH) Hub. “Echoing the observations made by the clinical teams, we saw profound and unique differences in the medical measurements of infected individuals, particularly in their full blood count data. It is these changes that we can train models to detect at scale.”

Unlike many current test methods, their approach doesn't require any prior knowledge of a specific pathogen to work, instead, they use full blood count data to exploit the pathogen detecting abilities of the human immune system by observing changes in the blood measurements associated with infection.

As the full blood count is the world’s most common medical laboratory test, with over 3.6 billion being performed worldwide each year, the BloodCounts! team can rapidly apply their methods to scan for abnormal changes in the blood cells of large populations - alerting public health agencies to potential outbreaks of pathogen infection.

This solution is a demonstration of how the application of AI-based methods can lead to healthcare benefits. It also highlights the importance of strong collaboration between leading organisations, as the development of these algorithms was only possible due the EpiCov data sharing initiative pioneered by Cambridge University Hospitals. 

“Hundreds of millions of full blood count tests are being performed every day worldwide, and this meant that we could apply our AI methods at population scale,” said Gleadall, from the University of Cambridge and NHS Blood and Transplant. “Usually the rich measurement data are discarded after summary results have been reported, but by working with Cambridge University, Barts Health London, and University College London NHS Hospitals we have rescued throughout the pandemic the rich data from 2.8 million full blood count tests.”

The Sentinel Forecasting System is the other second-prize winner, and will explore the emergence of new infectious diseases in West Africa, beginning with Lassa fever. The system will combine data from ecology, social science, genomics and epidemiology to provide real-time disease risk for haemorrhagic fevers, such as Lassa and Ebola.

Lassa is a virus usually passed to humans through exposure to food or household items contaminated by infected rats. It is endemic in West African countries including Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, Togo and Nigeria.

Around 80% of people who become infected with Lassa virus have no symptoms, and the overall case-fatality rate is 1%. 1 in 5 infections can result in severe disease affecting the liver, spleen and kidneys.

The UCL team will partner with the African Centre of Excellence for Genomics of Infectious Diseases in Nigeria, Nigeria Centre for Disease Control, Zoological Society of London, London School of Hygiene and Tropical Medicine, Microsoft, and Cambridge’s Laboratory of Viral Zoonotics (LVZ) to produce the system.

“This Trinity Challenge project brings new multidisciplinary technologies together to anticipate climatic, human, animal population, agricultural impacts on the likelihood of spill overs of infections from animals to humans,” said Professor Jonathan Heeney, who leads LVZ at Cambridge’s Department of Veterinary Medicine.

Additionally, five 3rd prize winners are each being awarded £480,000 (US$ 660,000) in pledged funding.

Dame Sally Davies said: “It was crystal clear at the beginning of this pandemic that the world had a lack of data, a lack of access to data, and a lack of interoperability of data, presenting a challenge. While others talked, we took action. The solutions we have discovered in the course of the Challenge will be a link between systems and countries.”

In addition to financial support, The Trinity Challenge will provide connections to the right organisations to maximise the impact of these solutions. Since its inception nine months ago, TTC has united early applicants with partners from the private, academic and social sectors to receive access to digital platforms, data, and technical advice, to scale-up the use of data and analytics to protect the world from future health emergencies. The Trinity Challenge has helped form over 200 connections between applicants and its members.

The Trinity Challenge has announced the winners of its inaugural competition, and is investing a £5.7 million (US$8 million) charitable pledged prize fund into one grand prize winner, two 2nd prize winners, and five 3rd prize winners.

medicinehealthPublic healthCarola-Bibiane SchönliebMichael RobertsNicholas GleadallJonathan HeeneySally DaviesDepartment of Applied Mathematics and Theoretical PhysicsCambridge Mathematics of Information in HealthcareDepartment of Veterinary MedicineSchool of the Physical SciencesSchool of Clinical MedicineSchool of the Biological SciencesTrinity CollegeJesus CollegeWhile others talked, we took action. The solutions we have discovered in the course of the Challenge will be a link between systems and countriesDame Sally DaviesThe Trinity ChallengeCollage of Trinity Challenge finalists


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Marmoset study identifies brain region linking actions to their outcomes

Thu, 24/06/2021 - 16:00

The study, published today in the journal Neuron, found that marmoset monkeys could no longer make an association between their behaviour and a particular outcome when a region of their brain called the anterior cingulate cortex was temporarily switched off.

This finding is important because the compulsive behaviours in OCD and addiction are thought to result from impairments in the 'goal-directed system' in the brain. In these conditions worrying, obsessions or compulsive behaviour such as drug seeking may reflect an alternative, habit-based system at work in the brain in which behaviours are not correctly linked with their outcomes.

It also sheds more light on how healthy people behave in a goal-directed way, which is needed to respond to changing environments and goals.

“We have identified the very specific region of the brain involved in goal-directed behaviour. When we temporarily turned this off, behaviour became more habitual - like when we go onto autopilot,” said Lisa Duan in the University of Cambridge’s Department of Psychology, first author of the report.

Marmosets were used because their brains share important similarities with human brains, and it is possible to manipulate specific regions of their brains to understand causal effects.

In the experiment, marmosets were first taught a goal-directed behaviour: by tapping a coloured cross when it appeared on a touchscreen, they were rewarded with their favourite juice to drink. But this connection between action and reward was randomly uncoupled so that they sometimes received the juice without having to respond to the image. They quickly detected this change and stopped responding to the image, because they saw they could get juice without doing anything.

Using drugs, the researchers temporarily switched off the anterior cingulate cortex including its connections with another brain region called the caudate nucleus. Repeating the experiment, they found when the connection between tapping the cross and receiving juice was randomly uncoupled, the marmosets did not change their behaviour but kept tapping the cross when it appeared.

Such habitual responding to the coloured cross was not observed when several other neighbouring regions of the brain’s prefrontal cortex - known to be important for other aspects of decision-making - were switched off. This shows the specificity of the anterior cingulate region for goal-directed behaviour.

A similar effect has been observed in computer-based tests on patients with Obsessive Compulsive Disorder (OCD) or addiction - when the relationship between an action and an outcome is uncoupled the patients continue to respond as though the connection is still there.

Previous evidence from patients suffering brain damage, and from brain imaging in healthy volunteers, shows that part of the brain called the prefrontal cortex is involved in goal-directed behaviour. However, the prefrontal cortex is a complex structure with many regions, and it has not previously been possible to identify the specific part responsible for goal-directed behaviour from human studies alone.

“We think this is the first study to have established the specific brain circuitry that controls goal-directed behaviour in primates, whose brains are very similar to human brains,” said Professor Angela Roberts in the University of Cambridge’s Department of Physiology, Development and Neuroscience, joint senior author of the report.

“This is a first step towards identifying suitable molecular targets for future drug treatments, or other forms of therapy, for devastating mental health disorders such as OCD and addiction,” added Professor Trevor Robbins in the University of Cambridge’s Department of Psychology, joint senior author of the report.

This research was conducted in the University of Cambridge’s Behavioural and Clinical Neuroscience Institute, and was funded by Wellcome.

Reference

Duan, L.Y. et al. ‘Controlling one’s world: identification of sub-regions of primate PFC underlying goal-directed behaviour.’ Neuron, June 2021. DOI: 10.1016/j.neuron.2021.06.003

Researchers have discovered a specific brain region underlying ‘goal-directed behaviour’ – that is, when we consciously do something with a particular goal in mind, for example going to the shops to buy food.

animal researchNeuroscienceLisa DuanAngela RobertsTrevor RobbinsDepartment of PsychologyDepartment of Physiology, Development and Neuroscience (PDN)Cambridge NeuroscienceDowning CollegeSchool of the Biological SciencesThis is a first step towards identifying suitable molecular targets for future drug treatments, or other forms of therapy, for devastating mental health disorders such as OCD and addiction.Trevor RobbinsMarmoset


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Study shows brain differences in interpreting physical signals in mental health disorders

Tue, 22/06/2021 - 02:16

The researchers, from the University of Cambridge, found that the part of the brain which interprets physical signals from the body behaves differently in people with a range of mental health disorders, suggesting that it could be a target for future treatments.

The researchers studied ‘interoception’ – the ability to sense internal conditions in the body – and whether there were any common brain differences during this process in people with mental health disorders. They found that a region of the brain called the dorsal mid-insula showed different activity during interoception across a range of disorders, including depression, schizophrenia, eating disorders and anxiety disorders.

Many people with mental health disorders experience physical symptoms differently, whether that’s feeling uncomfortably full in anorexia, or feeling like you don’t have enough air in panic disorder.

The results, reported in The American Journal of Psychiatry, show that activity in the dorsal mid-insula could drive these different interpretations of bodily sensations in mental health. Increased awareness of the differences in how people experience physical symptoms could also be useful to those treating mental health disorders.

We all use exteroception – sight, smell, hearing, taste and touch – to navigate daily life. But interoception – the ability to interpret signals from our body – is equally important for survival, even though it often happens subconsciously.

“Interoception is something we are all doing constantly, although we might not be aware of it,” said lead author Dr Camilla Nord from the MRC Cognition and Brain Sciences Unit. “For example, most of us are able to interpret the signals of low blood sugar, such as tiredness or irritability, and know to eat something. However, there are differences in how our brains interpret these signals.”

Differences in interoceptive processes have previously been identified in people with eating disorders, anxiety and depression, panic disorder, addiction and other mental health disorders. Theoretical models have suggested that disrupted cortical processing drives these changes in interoceptive processing, conferring vulnerability to a range of mental health symptoms.

Nord and her colleagues combined brain imaging data from previous studies and compared differences in brain activity during interoception between 626 patients with mental health disorders and 610 healthy controls. “We wanted to find out whether there is something similar happening in the brain in people with different mental disorders, irrespective of their diagnosis,” she said.

Their analysis showed that for patients with bipolar, anxiety, major depression, anorexia and schizophrenia, part of the cerebral cortex called the dorsal mid-insula showed different brain activation when processing pain, hunger and other interoceptive signals when compared to the control group.

The researchers then ran a follow-up analysis and found that the dorsal mid-insula does not overlap with regions of the brain altered by antidepressant drugs or regions altered by psychological therapy, suggesting that it could be studied as a new target for future therapeutics to treat differences in interoception.

“It’s surprising that in spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders,” said Nord. “It shows how intertwined physical and mental health are, but also the limitations of our diagnostic system – some important factors in mental health might be ‘transdiagnostic’, that is, found across many diagnoses.”

In future, Dr Nord is planning studies to test whether this disrupted activation could be altered by new treatments for mental health disorders, such as brain stimulation.

The research was supported by NIHR Cambridge Biomedical Research Centre.

Reference:
Camilla L. Nord, Rebecca P. Lawson and Tim Dalgleish. ‘Disrupted dorsal mid-insula activation during interoception across psychiatric disorders.’ The American Journal of Psychiatry (2021). DOI: 10.1176/appi.ajp.2020.20091340

 

Researchers have shown why people with mental health disorders, including anorexia and panic disorders, experience physical signals differently.

Neurosciencebrainmental healthsensesCamilla NordCambridge University Health PartnersMRC Cognition and Brain Sciences UnitSchool of Clinical MedicineIn spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders: it shows how intertwined physical and mental health areCamilla NordGeralt from PixabayBinary code


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Targeting cellular response to SARS-CoV-2 holds promise as new way to fight infection

Thu, 17/06/2021 - 19:00

When a person is infected with SARS-CoV-2, the virus that causes COVID-19, it invades their cells and uses them to replicate - which puts the cells under stress. Current approaches to dealing with infection target the virus itself with antiviral drugs. But Cambridge scientists have switched focus to target the body’s cellular response to the virus instead. 

In a new study, published today in the journal PLOS Pathogens, they found that all three branches of a three-pronged signalling pathway called the ‘unfolded protein response’ (UPR) are activated in lab-grown cells infected with SARS-CoV-2. Inhibiting the UPR to restore normal cell function using drugs was also found to significantly reduce virus replication.

“The virus that causes COVID-19 activates a response in our cells - called the UPR - that enables it to replicate,” said Dr Nerea Irigoyen in the University of Cambridge’s Department of Pathology, senior author of the report.

She added: “Using drugs we were able to reverse the activation of this specific cellular pathway, and remarkably this reduced virus production inside the cells almost completely, which means the infection could not spread to other cells. This has exciting potential as an anti-viral strategy against SARS-CoV-2.” 

Treatment with a drug that targets one prong of the UPR pathway had some effect in reducing virus replication. But treatment with two drugs together - called Ceapin-A7 and KIRA8 - to simultaneously target two prongs of the pathway reduced virus production in the cells by 99.5%. This is the first study to show that the combination of two drugs has a much greater effect on virus replication in cells than a single drug. 

The approach would not stop a person getting infected with the coronavirus, but the scientists say symptoms would be much milder, and recovery time would be quicker.

Anti-viral drugs currently in use to treat COVID-19, such as remdesivir, target replication of the virus itself. But if the virus develops resistance to these drugs they will no longer work. In contrast, the new treatment targets the response of the infected cells; this will not change even if new variants emerge, because the virus needs this cellular response in order to replicate.

The next step is to test the treatment in mouse models. The scientists also want to see whether it works against other viruses, and illnesses such as pulmonary fibrosis and neurological disorders that also activate the UPR response in cells. 

“We hope this discovery will enable the development a broad-spectrum anti-viral drug, effective in treating infections with other viruses as well as SARS-CoV-2. We’ve already found it has an effect on Zika virus too. It has the potential to have a huge impact,” said Irigoyen.

SARS-CoV-2 is the novel coronavirus responsible for the COVID-19 pandemic. Since the end of 2019 there have been over 150 million cases of the disease worldwide, and over 3 million people have died. 

This research was funded by an Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grant.

Reference
Echavarria-Consuegra, L. et al: ‘Manipulation of the unfolded protein response: a pharmacological strategy against coronavirus infection.’ PLOS Pathogens. May 2021. DOI:10.1371/journal.ppat.1009644

 

A new treatment approach focused on fixing cell damage, rather than fighting the virus directly, is effective against SARS-CoV-2 in lab models. If found safe for human use, this anti-viral treatment would make COVID-19 symptoms milder and speed up recovery times.

CoronavirusCOVID-19Infectious diseasesNerea IrigoyenDepartment of PathologyCambridge Infectious DiseasesSchool of the Biological SciencesCredit: NIAIDScanning electron microscope image of SARS-CoV-2 (orange) emerging from the surface of cells (green) cultured in the lab.


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: AttributionNews type: News

Study identifies trigger for ‘head-to-tail’ axis development in human embryo

Thu, 17/06/2021 - 10:06

The second week of gestation represents a critical stage of embryo development, or embryogenesis. Failure of development during this time is one of the major causes of early pregnancy loss. Understanding more about it will help scientists to understand how it can go wrong, and take steps towards being able to fix problems.

The pre-implantation period, before the developing embryo implants into the mother’s womb, has been studied extensively in human embryos in the lab. On the seventh day the embryo must implant into the womb to survive and develop. Very little is known about the development of the human embryo once it implants, because it becomes inaccessible for study.

Pioneering work by Professor Magdalena Zernicka-Goetz and her team developed a technique, reported in 2016, to culture human embryos outside the body of the mother beyond implantation. This enabled human embryos to be studied up to day 14 of development for the first time. 

In a new study, the team collaborated with colleagues at the Wellcome Sanger Institute to reveal what happens at the molecular level during this early stage of embryogenesis. Their findings provide the first evidence that a group of cells outside the embryo, known as the hypoblast, send a message to the embryo that initiates the development of the head-to-tail body axis. 

When the body axis begins to form, the symmetrical structure of the embryo starts to change. One end becomes committed to developing into the head end, and the other the ‘tail’. 

The new results, published today in the journal Nature Communications, reveal that the molecular signals involved in the formation of the body axis show similarities to those in animals, despite significant differences in the positioning and organisation of the cells.

“We have revealed the patterns of gene expression in the developing embryo just after it implants in the womb, which reflect the multiple conversations going on between different cell types as the embryo develops through these early stages,” said Professor Magdalena Zernicka-Goetz in the University of Cambridge’s Department of Physiology, Development and Neuroscience, and senior author of the report.

She added: “We were looking for the gene conversation that will allow the head to start developing in the embryo, and found that it was initiated by cells in the hypoblast – a disc of cells outside the embryo. They send the message to adjoining embryo cells, which respond by saying ‘OK, now we’ll set ourselves aside to develop into the head end.’”

The study identified the gene conversations in the developing embryo by sequencing the code in the thousands of messenger RNA molecules made by individual cells. They captured the evolving molecular profile of the developing embryo after implantation in the womb, revealing the progressive loss of pluripotency (the ability of the embryonic cells to give rise to any cell type of the future organism) as the fates of different cells are determined.

“Our goal has always been to enable insights to very early human embryo development in a dish, to understand how our lives start. By combining our new technology with advanced sequencing methods we have delved deeper into the key changes that take place at this incredible stage of human development, when so many pregnancies unfortunately fail,” said Zernicka-Goetz.

This research was funded by Wellcome. It was carried out with the oversight of the UK Human Fertilisation and Embryology Authority, and with permission from a local research ethics committee.

Reference: Mole, M.A. et al: ‘A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.’ Nature Communications, June 2021. DOI: 10.1038/s41467-021-23758-w 

 

Scientists have identified key molecular events in the developing human embryo between days 7 and 14 - one of the most mysterious, yet critical, stages of our development. 

ReproductionMagdalena Zernicka-GoetzWellcome Sanger InstituteDepartment of Physiology, Development and Neuroscience (PDN)Cambridge Reproduction Strategic Research InitiativeSchool of the Biological SciencesWe have revealed the patterns of gene expression in the developing embryo just after it implants in the wombMagdalena Zernicka-GoetzHuman embryo in the lab 9 days after fertilisation.


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesNews type: News

Teenagers at greatest risk of self-harming could be identified almost a decade earlier

Tue, 15/06/2021 - 07:00

The team, based at the MRC Cognition and Brain Sciences Unit, University of Cambridge, found that while sleep problems and low self-esteem were common risk factors, there were two distinct profiles of young people who self-harm – one with emotional and behavioural difficulties and a second group without those difficulties, but with different risk factors.

Between one in five and one in seven adolescents in England self-harms, for example by deliberately cutting themselves. While self-harm is a significant risk factor for subsequent suicide attempts, many do not intend suicide but face other harmful outcomes, including repeatedly self-harming, poor mental health, and risky behaviours like substance abuse. Despite its prevalence and lifelong consequences, there has been little progress in the accurate prediction of self-harm.

The Cambridge team identified adolescents who reported self-harm at age 14, from a nationally representative UK birth cohort of approximately 11,000 individuals. They then used a machine learning analysis to identify whether there were distinct profiles of young people who self-harm, with different emotional and behavioural characteristics. They used this information to identify risk factors from early and middle childhood. The results are published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Because the data tracked the participants over time, the researchers were able to distinguish factors that appear alongside reported self-harm behaviour, such as low self-esteem, from those that precede it, such as bullying.

The team identified two distinct subgroups among young people who self-harm, with significant risk factors present as early as age five, nearly a decade before they reported self-harming. While both groups were likely to experience sleep difficulties and low self-esteem reported at age 14, other risk factors differed between the two groups.

The first group showed a long history of poor mental health, as well as bullying before they self-harmed. Their caregivers were more likely to have mental health issues of their own.

For the second group, however, their self-harming behaviour was harder to predict early in childhood. One of the key signs was a greater willingness to take part in risk-taking behaviour, which is linked to impulsivity. Other research suggests these tendencies may predispose the individual towards spending less time to consider alternate coping methods and the consequences of self-harm. Factors related to their relationships with their peers were also important for this subgroup, including feeling less secure with friends and family at age 14 and a greater concern about the feelings of others as a risk factor at age 11.

Stepheni Uh, a Gates Cambridge Scholar and first author of the study, said: “Self-harm is a significant problem among adolescents, so it’s vital that we understand the nuanced nature of self-harm, especially in terms of the different profiles of young people who self-harm and their potentially different risk factors.

“We found two distinct subgroups of young people who self-harm. The first was much as expected – young people who experience symptoms of depression and low self-esteem, face problems with their families and friends, and are bullied. The second, much larger group was much more surprising as they don’t show the usual traits that are associated with those who self-harm.”

The researchers say that their findings suggest that it may be possible to predict which individuals are most at risk of self-harm up to a decade ahead of time, providing a window to intervene.

Dr Duncan Astle said: “The current approach to supporting mental health in young people is to wait until problems escalate. Instead, we need a much better evidence base so we can identify who is at most risk of mental health difficulties in the future, and why. This offers us the opportunity to be proactive, and minimise difficulties before they start.

“Our results suggest that boosting younger children’s self-esteem, making sure that schools implement anti-bullying measures, and providing advice on sleep training, could all help reduce self-harm levels years later.

“Our research gives us potential ways of helping this newly-identified second subgroup. Given that they experience difficulties with their peers and are more willing to engage in risky behaviours, then providing access to self-help and problem-solving or conflict regulation programmes may be effective.”

Professor Tamsin Ford from the Department of Psychiatry added: “We might also help at-risk adolescents by targeting interventions at mental health leaders and school-based mental health teams. Teachers are often the first people to hear about self-harm but some lack confidence in how to respond. Providing them with training could make a big difference.”

The research was supported by the Gates Cambridge Trust, Templeton World Charity Foundation, and the UK Medical Research Council.

Reference
Uh, S et al. Two pathways to self-harm in adolescence. Journal of the American Academy of Child and Adolescent Psychiatry; 14 June 2021; DOI: 10.1016/j.jaac.2021.03.010

Researchers have identified two subgroups of adolescents who self-harm and have shown that it is possible to predict those individuals at greatest risk almost a decade before they begin self-harming.

mental healthChildrenrisk factorSpotlight on neuroscienceNeuroscienceDuncan AstleStepheni UhTamsin FordMedical Research CouncilGates Cambridge TrustTempleton World Charity FoundationMRC Cognition and Brain Sciences UnitDepartment of PsychiatrySchool of Clinical MedicineThe current approach to supporting mental health in young people is to wait until problems escalate. Instead, we need a much better evidence base so we can identify who is at most risk of mental health difficulties in the future, and whyDuncan AstleAdrien OlichonA man sitting in front of a screen


The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

YesLicense type: Public DomainNews type: News