̽��ֱ�� of Cambridge - ̽��ֱ��Conversation

Q&A with Sharon Peacock, coronavirus variant hunter

cjb250 — Mon, 22 Feb 2021 13:35:28 +0000

̽��ֱ��Conversation spoke to Professor Peacock about that day and what happened after.

Q: When did you first get the idea to set up Cog-UK? And how was it formed?

In late February 2020, it dawned on me that we were going to need genome sequencing capabilities across the UK for the novel coronavirus. It was predictable that the virus was going to develop mutations that could become problematic.

On March 4, I emailed five colleagues, asking if they’d be interested in helping me set up a UK sequencing consortium. A week later we met at the Wellcome building on Euston Road in London with the aim of thrashing out a plan. We looked to draw in people who might be able to help us put together a blueprint and a network for sequencing in the UK.

There were about 20 people in the meeting. They were clinical virologists, experts in human genomes and pathogen genomes, epidemiologists and immunologists. During that day, we worked through what we thought an end-to-end sequencing pipeline would be, and we debated whether the sequencing would be centralised or distributed or both, and who would do what. By the end of the day, we had the blueprint.

̽��ֱ��notes from the meeting were written up into a formal proposal for Sir Patrick Vallance, the UK government’s chief scientific adviser.

It’s unusual because if you have four public health agencies and lots of researchers from different institutions and the NHS, it would take a year or more to do something like that normally. But we just sat down and did it, and that’s how Cog-UK was born.

Q: How did you get funding?

̽��ֱ��application was on Sir Patrick Vallance’s desk by March 15. He and Professor Chris Whitty, the chief medical officer for England, had what they called a “COVID-19 fighting fund”. They reviewed our proposal and strongly supported it.

I also contacted Sir Mike Stratton, director of the Wellcome Sanger Institute in Cambridge. I asked Mike if they could support us as they have the technology to do large-scale sequencing. He said yes, and since then, Sanger has contributed a great deal.

So at the outset, we got about £14.5 million from the government, plus in-kind funding from Sanger, which together came to a total of around £20 million.

We started on April 1, but we’d already done quite a lot of sequencing by then. About 260 coronavirus sequences were already in the bag.

Q: So the sequencing began even before Cog-UK was launched?

Because a lot of people had sequencing instruments and expertise, they had already started work. There are sequencing instruments in labs across the country. We hadn’t catalogued where or what at that stage. And, in fact, we weren’t particularly prescriptive about what types of sequencing instruments we asked the labs to use. People used what they thought worked well for them.

Q: How did other scientists react?

They were hugely supportive. Some people were worried that the virus would not accumulate enough mutations to make it worth our while. It would mean that we would end up sequencing the same virus over and over again because it only mutates once or twice a month. It could all have been a waste of time.

What we hadn’t bargained for was the 100 million cases – but perhaps even as high as a billion, if you include undiagnosed cases. And each time the virus infects a person it has an opportunity to make a mistake in its genome.

We considered the risk of lack of genetic variation, but went ahead. What we did was rather bold at the time.

Q: How does it work in practice, from the time someone is swabbed to the time the sequence is uploaded onto the shared Gisaid database that holds all of the world’s sequences of SARS-CoV-2?

Laboratory testing for COVID-19 using the so-called PCR test in the UK is roughly divided into two testing pathways. If you are hospitalised with COVID-19, your sample will get tested in a local laboratory. We call that pillar one.

Cog-UK collects samples from about 90 different laboratories at the moment, which is quite a logistical challenge. These are sent to regional sequencing hubs that focus mostly on sequencing from their region. These are really important samples because they are from the sickest people with COVID-19.

Pillar two testing is done in the Lighthouse labs, which were set up to analyse community testing samples. These are sequenced at the Wellcome Sanger Institute.

We also provide sequencing to major government projects, like the Office for National Statistics study. We also support the React study, [a major programme of home testing for COVID-19 to track the progress of the infection across England] and vaccine trials.

We can’t sequence all of the positive samples at the moment. When we first started, we were aiming for a minimum of 10%. At the moment it’s under 10%, but we hope to get to around 20%, and we’ll build from there.

Q: And as a total of the viruses sequenced in the world, what proportion is Cog-UK sequencing, and how does it compare with other countries?

We have sequenced about 45% to 48% of all SARS-CoV-2 genomes in the Gisaid database.

Q: Given the importance of tracking mutations, are other countries starting to increase their sequencing efforts?

Yes. ̽��ֱ��country where I think we will see a big shift is the US because of all the changes they’re making in their response to the pandemic. I would anticipate quite a few other countries beginning to come up, too. I know that Germany is looking to increase its sequencing capacity. But there are some really big gaps in the map.

Q: Worrying coronavirus variants have been widely reported on in the last few months. ̽��ֱ��so-called “UK variant”, B117, was raised as a concern in November, but the sample was from September. Is that right?

Yes, September 20. There were very few cases of B117 initially, and it’s one of hundreds of different variants. So there was no reason to be concerned about it initially. We are learning all the time about which mutations might be important, particularly when they crop up all around the world. So the first time the UK variant was in the database, you probably wouldn’t give it a second thought. It’s only once you start to learn about what the mutations really mean, or when an event occurs, that you start to zoom in on specific variants. And with B117, Public Health England noticed that there was a surge in cases in Kent, which was odd because there was a lockdown and there weren’t any surges elsewhere. That was a striking observation.

So that could be due to human behaviour, such as a super-spreader event. It was at that point, towards the beginning of December, that it became clear that there was not only a surge in cases, but those cases were caused by B117. It had a really striking genome in that it had 23 mutations, which were far more than we were used to seeing. That’s when researchers began to find evidence that it was more transmissible. And it took a bit longer to do the essential science so that we could be certain that this variant was indeed associated with increased transmission.

Q: Why are we suddenly seeing all of these mutations that give the coronavirus an advantage now?

It’s not the first time that we have observed mutations that have given the virus an advantage. At the end of March 2020, we noticed something for the first time in the UK: a mutation in the spike protein called D614G. This wasn’t in the original virus that was first detected in China. But the virus with this mutation rapidly expanded and replaced the other viral lineages circulating at the time.

We talked about this at Sage, the government’s scientific advisory group for emergencies, quite early on. And we calculated that it caused an increase in the R0, which represents the average number of people infected by one infectious individual. So we knew then that this type of event could happen – it was a practice run for more serious variants to come.

̽��ֱ��D614G mutation gave the virus a modest increase in transmissibility. But it swept across the world. It’s now present in almost all SARS-CoV-2 viruses.

̽��ֱ��next variant to worry people emerged in Denmark and was related to SARS-CoV-2 being transmitted between mink and people – referred to as the “cluster 5 variant”. People were concerned that evolution had been accelerated by passage through mink and had been transmitted back to humans. But only 12 people in Denmark were ever found to have that variant. So that fizzled.

A third worrying variant emerged in Spain in the summer. It seemed to be spreading very quickly around Europe. One possible reason for this was a particular mutation in the spike protein. But over time it became clear that it was being transmitted because people were moving around on their summer holidays. There was no evidence that it was more transmissible.

We also reported to Sage another mutation in the spike protein last October, called N439K. And that change in the spike protein appears to affect the body’s immune response, at least based on laboratory experiments.

So the idea that variants have only just arisen is not the case. We’ve been talking about variants since the early days of the pandemic, which might surprise some people.

Q: Is the original virus from Wuhan still around?

Lineages can expand and then go extinct, so we don’t expect the same lineage to necessarily be around forever. This was shown by work in Wales and in Scotland, where they looked at the lineages in the first wave and then in the second wave.

In the first wave, these were largely imported from Europe. In the summer as cases fell, most of those original lineages disappeared. Then, in the second wave, numerous new lineages were introduced from overseas, which kicked off the second wave. So it’s quite a dynamic process. As particular lineages have a fitness advantage, then that is probably what is circulating at any particular time.

Q: Is there a base type that you compare changes against? And is it the original virus or the current dominant variant?

We compare changes against the original virus sequenced in Wuhan in January 2020 – it’s the reference genome. But it’s quite confusing because different groups use different names and different naming conventions. I hope that the World Health Organization will help us to reach a common international nomenclature.

It worries me that people name variants after where they were first identified. Evolution is not a function of geography, it’s a function of nature. I very much hope that we move away from calling coronaviruses, the UK variant or the South African variant or the Brazilian variant. I tend to try and say the variant first detected in South Africa, or whatever. Because it could be quite stigmatising in the longer term.

Q: Is a certain amount of evolutionary selective pressure created when we start to vaccinate lots of people? Or is the greater number of people in which the virus has the opportunity to mutate the greater problem of the two?

At the moment, I think it’s the number of cases that is important because the variant detected in the UK emerged when vaccines weren’t yet being rolled out, but when cases were high. And the same is true in South Africa and Brazil.

Some people have contacted me to say: “Do you think it was the vaccine trials that led variants to emerge?” But if you compare the relatively small number of people who’ve been in vaccine trials versus the very large number of people who are infected – 100 million people infected. I think the biggest driver of mutation emerging is the number of opportunities the virus has had to mutate.

And people say, “Well, isn’t the vaccine going to drive the emergence of new variants?” It may be one of the pressures, but if you’re in a population where, say, 50% have been infected and have so-called “natural immunity”, then it doesn’t matter how you get the immunity to the virus, the virus will try to find a crack in that armour. But in that instance, it’s a naturally acquired infection rather than immunisation. So this problem has been around long before vaccination.

Q: And of the variants of concern that we know of, which one is the most worrying?

Right now, it’s the variant first detected in South Africa. It has already been reported in 31 countries and identified in 750 sequences so far. Although this is probably a gross underestimate because quite a few countries that surround South Africa do not have sequencing capacity at the moment. This variant appears to be more transmissible in South Africa and reduces the effectiveness of our immune response, be that from natural infection or vaccination.

P1 is also on the watch list. This variant first identified in Brazil has mutations associated with being more transmissible and with a reduced immune response. If you look at the global spread of P1 though, unlike some of the other variants, I don’t really see it taking hold at the moment. It’s been linked to just nine countries so far.

I’m also looking at what else might be emerging in the coming weeks and months. What I’m particularly concerned about is that now that B117 causes almost all COVID-19 cases in the UK – what new mutations will arise in this? This new variant is likely to start to develop constellations of different mutations in its descendants. And what I’m watching for is something like E484K, the “escape mutation”, being increasingly found in B117. So far, this has arisen independently several times and includes a cluster of cases in Bristol and south-west England, but the number of cases is low.

Q: How important is what Cog-UK does to the vaccine effort?

Sequencing is absolutely integral to vaccine development. We are going to need to have sequence data.

We’re going to need to keep sequencing for the foreseeable future so that we can adapt our vaccines to keep them effective. It’s going to be a long-term job to run the two in parallel. Vaccine manufacturers are already working to tweak their vaccines for the South Africa variant, for example, to make sure it’s going to be effective against that variant.

There are going to be new variants arising in the future and we’re going to have to adapt our response to these as we go along. Sequencing and vaccine development are key partners. I suspect that this is going to be ongoing throughout my life and beyond. Of concern is that we don’t have global coverage, so we are not sighted globally in terms of new variants.

Q: So it’s going to be like the flu vaccine every year, depending on how long immunity lasts?

Yes, quite similar, but it might be a bit less predictable than a single vaccine booster each year. SARS-CoV-2 could ratchet up its characteristics over time, and the diversity of mutation combinations in different variants could change over time. So it could be more complex than flu.

We’ve also known that immunity wanes over time. So we’re going to have to be thinking about long-term strategies with this virus.

Sharon Peacock, Director, COVID-19 genomics UK Consortium (COG-UK) and Professor of Public Health & Microbiology, ̽��ֱ�� of Cambridge

This article is republished from ̽��ֱ��Conversation under a Creative Commons license. Read the original article.

̽��ֱ��UK is a world leader in sequencing SARS-CoV-2, the virus that causes COVID-19. Of all the coronavirus genomes that have been sequenced in the world, nearly half have been sequenced by COVID-19 Genomics UK Consortium (Cog-UK). ̽��ֱ��consortium began life on 4 March 2020 when Sharon Peacock, a professor of public health and microbiology at the ̽��ֱ�� of Cambridge, emailed a handful of scientists and asked for their help.

Professor Sharon Peacock

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� 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.

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Opinion: Depression - men far more at risk than women in deprived areas

Anonymous — Wed, 27 Nov 2019 10:10:38 +0000

Depression is a major cause of disability around the world, and if left untreated, can lead to substance abuse, anxiety and suicide.

Major depressive disorder is a particular form of the condition which affects many people, potentially causing loss of pleasure in activities that once used to bring joy. It can also lead to feelings of worthlessness, imbalances such as oversleeping or insomnia, and trigger thoughts of suicide. This is the condition we examined during our new study, which showed that living in a deprived area can lead to major depressive disorder in men, but not in women.

Before explaining these findings, it is important to provide some further background on this condition. There are certain factors which can place you at increased risk for major depression. Being diagnosed with a serious chronic ailment, such as diabetes or cancer, now or in the past, can increase your risk for it. As can experiences of trauma, such as physical or sexual abuse, or being raised in a dysfunctional family in which there was a high degree of marital discord.

These, however, are all individual factors – or personal circumstances – which can negatively affect your mental health. And most of the research on depression has indeed focused on such personal factors. But there are characteristics beyond the level of the individual – such as attributes of the communities in which we live – that can also have a profound effect on our mental well-being.

Previous studies have shown that living in communities characterised as deprived can lead residents of those areas to rate their health as suboptimal and experience early death. Through our study, we wanted to know if living in a deprived area can also influence the mental health of men and women – even after accounting for personal circumstances. That is, even after you take people’s socioeconomic status into account (in our study’s case, education and social class), does a person’s residential environment still affect their mental health?

̽��ֱ��findings

To answer this question, we used data from one of Britain’s longest-running studies on health, chronic diseases, and the way people live their lives: EPIC-Norfolk. This study was based on over 20,000 people who filled out detailed questionnaires on their mental health and medical history.

Respondents’ postal codes were linked to the census to determine whether they lived in deprived communities. Five years after deprivation levels were measured, participants filled out a psychosocial questionnaire to determine whether they suffered from major depressive disorder. Using statistical techniques, the association between area deprivation and depression was examined while accounting for medical history, education, social class, and other important factors.

Our study showed that living in a deprived area does affect mental health – at least in men. In fact, we found that men living in the most deprived areas were 51% more likely to experience depression than those living in areas that were not deprived. Interestingly, the results did not reach statistical significance in women.

Loss of purpose. Shutterstock

Our study did not set out to determine why this might be the case – and further research is now needed to do this. Nevertheless, it is possible that many men in the UK and other parts of the world still feel a primary responsibility to provide for and support their families.

A recent study investigating depression risks for men and women indicated that men are more affected by “failures at key instrumental tasks, such as expected work achievements and failures to provide adequately for the family”.

Research shows that men seem to be more sensitive to certain stressors in their environment compared to women, such as those related to work and finances. Women’s depression levels, on the other hand, are more influenced by stressors stemming from relationships and the social networks they are embedded in. Factors such as low parental warmth and low marital satisfaction, for example, can really affect women’s mental health.

A great many factors may be behind this, but in the UK, men are three times more likely to die by suicide than women and so root causes as to why men are struggling should be investigated.

While women are at a lower risk of depression than men in deprived areas, other research shows that they are more likely to experience anxiety. Again, further work is needed on the effect of the residential environment on mental health from a gender perspective.

High numbers of people are living in deprivation around the world and depression is a leading cause of disability on a global scale. Knowing how men and women are affected by the hardship of living in deprivation can help focus mental health treatment, and this is a valuable step forward.

This article is republished from ̽��ֱ��Conversation under a Creative Commons license. Read the original article.

Deprivation affects men and women differently, writes Olivia Remes, PhD candidate at the Cambridge Institute of Public Health, with men more likely to experience depression.

Andrik Langfield

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Loneliness is contagious – and here's how to beat it

cjb250 — Mon, 16 Jul 2018 10:07:10 +0000

Loneliness is a common condition affecting around one in three adults. It damages your brain, immune system, and can lead to depression and suicide. Loneliness can also increase your risk of dying prematurely as much as smoking can – and even more so than obesity. If you feel lonely, you tend to feel more stressed in situations that others cope better in, and even though you might get sufficient sleep, you don’t feel rested during the day.

Loneliness has also increased over the past few decades. Compared to the 1980s, the number of people living alone in the US has increased by about one-third. When Americans were asked about the number of people that they can confide in, the number dropped from three in 1985 to two in 2004.

In the UK, 21% to 31% of people report that they feel lonely some of the time, and surveys in other parts of the world report similarly high estimates. And it’s not just adults who feel lonely. Over a tenth of kindergarteners and first graders report feeling lonely in the school environment.

Loneliness is common among children, too. Shutterstock

So many people feel lonely these days. But loneliness is a tricky condition, because it doesn’t necessarily refer to the number of people you talk to or the number of acquaintances you have. You can have many people around you and still feel lonely. As the comedian Robin Williams put it in the film World’s Greatest Dad:

I used to think the worst thing in life was to end up all alone. It’s not. ̽��ֱ��worst thing in life is to end up with people who make you feel all alone.

What is loneliness?

Loneliness refers to the discrepancy between the number and quality of the relationships that you desire and those you actually have. You can have only two friends, but if you get along really well with them and feel that they meet your needs, you’re not lonely. Or you can be in a crowd and feel all alone.

But loneliness is not just about how you feel. Being in this state can make you behave differently, too, because you have less control over yourself – for example, you’re more likely to eat that chocolate cake for lunch instead of a meal or order take-out for dinner and you will also feel less motivated to exercise, which is important for mental and physical health. You’re also more likely to act aggressively towards others.

Sometimes people think that the only way out of loneliness is to simply talk to a few more people. But while that can help, loneliness is less about the number of contacts that you make and more about how you see the world. When you become lonely, you start to act and see the world differently. You begin noticing the threats in your environment more readily, you expect to be rejected more often, and become more judgemental of the people you interact with. People that you talk to can feel this, and as a result, start moving away from you, which perpetuates your loneliness cycle.

Studies have shown that (non-lonely) people who hang out with lonely people are more likely to become lonely themselves. So loneliness is contagious, just as happiness is – when you hang out with happy people, you are more likely to become happy.

There is also a loneliness gene that can be passed down and, while inheriting this gene doesn’t mean you will end up alone, it does affect how distressed you feel from social disconnection. If you have this gene, you are more likely to feel the pain of not having the kinds of relationships that you want.

It’s particularly bad news for men. Loneliness more often results in death for men than for women. Lonely men are also less resilient and tend to be more depressed than lonely women. This is because men are typically discouraged from expressing their emotions in society and if they do they are judged harshly for it. As such, they might not even admit it to themselves that they’re feeling lonely and tend to wait a long time before seeking help. This can have serious consequences for their mental health.

How to escape it

Look at being alone in a new light. Shutterstock

To overcome loneliness and improve our mental health, there are certain things we can do. Research has looked at the different ways of combating this condition, such as increasing the number of people you talk to, improving your social skills, and learning how to compliment others. But it seems the number one thing is to change your perceptions of the world around you.

It’s realising that sometimes people aren’t able to meet up with you, not because there is something inherently wrong with you, but because of other things going on in their lives. Maybe the person that you wanted to have dinner with wasn’t able to accept your invitation because it was too short notice for them and they had already promised someone else they would have drinks. People who aren’t lonely realise this and, as a consequence, don’t get down or start beating themselves up when someone says no to their invitations. When you don’t attribute “failures” to yourself, but rather to circumstances, you become much more resilient in life and can keep going.

Getting rid of loneliness is also about letting go of cynicism and mistrust of others. So next time you meet someone new, try to lose that protective shield and really allow them in, even though you don’t know what the outcome will be.

Olivia Remes, PhD Candidate, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

One in three adults is affected by loneliness. It's time for us to take a risk and let others into our lives, says Olivia Remes, PhD candidate at the Cambridge Institute of Public Health, writing for ̽��ֱ��Conversation.

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Ditching the car may reduce your risk of dying from heart disease and stroke by almost a third

cjb250 — Tue, 22 May 2018 08:35:21 +0000

Swapping your car for more physically active forms of travel may reduce your risk of heart disease, stroke and premature death, our latest research shows. Walking, cycling and even using public transport are all more physically active than using the car, so switching to one of these modes of transport can help you be more active and healthy.

Most physical activity studies focus on sport and recreational activity – intense activities often lasting many minutes. We are interested in understanding the impact of everyday activity on health. People lead busy lives. ̽��ֱ��challenge is to find ways for people to be active and stay active throughout life. For many, everyday activity, like walking or cycling for travel, may be more acceptable, attractive and practical than going to the gym.

For our analysis, we used a large cohort of over 350,000 adults, aged 37 to 73, from the UK Biobank study. At the start of the study people told us about their travel habits, as well as other important health behaviours, such as smoking. We compared people who only used the car for travel with those who undertook some walking, either alone or in combination with the car or public transport. People who cycled were also included in the active group, although few people in our study cycled.

We carried out separate analyses for those who regularly commuted and those who did not.

Some people prefer stairs to a Stairmaster. JuneChalida/Shutterstock.com

Clear pattern

This was an observational study, so we can’t say definitively that car use causes harm. However, we took many steps to rule out other factors, such as what people eat or underlying illness that might explain the findings. For example, people with poor health might have to use the car because their poor health limits their ability to get around. Their poor health might explain their higher risk of disease. We used statistical methods to adjust for this, and, in some cases, we removed these people from the analysis. While we have tried to eliminate these other factors, we can never be sure we have done this entirely.

Among people who commuted, more active patterns of commuting compared with exclusive car use were associated with an 11% lower relative risk of developing heart disease or stroke and a 30% lower relative risk of death from heart disease or stroke. ̽��ֱ��association was even stronger when we looked across all forms of travel, both commuting and everyday travel.

Nearly half our sample did not commute. These people were retired, not in employment or they worked from home. Few studies have looked at these people. Among these people, more active patterns of travel compared with exclusive car use were associated with an 8% lower relative risk of death.

Although not all of our findings reached statistical significance, there was an overall pattern. More active patterns of travel, compared with exclusive car use, were associated with reduced risk of heart disease, stroke and death.

Areas still to explore

It would have been interesting to dig deeper and understand the relative importance of different patterns of travel. How beneficial is public transport compared with car use? Is there an additional benefit of cycling over walking? But, unfortunately, we couldn’t do that with the data we had.

Different data might also have allowed us to better understand why. Other people have suggested that snacking in cars might be a contributory factor, although we think the most likely explanation is differences in physical activity.

Our research builds on what is already widely known about the health benefits of physical activity. Some people may choose to use cars less when they understand the impacts on health. But many people may not have a choice. Others may just do what is convenient, comfortable and normal.

̽��ֱ��large differences in travel patterns between cities in developed countries seem most likely to be explained by differences in infrastructure. There have been large increases in public transport use and consequently walking in London, after investment in these travel modes. ̽��ֱ��Netherlands made a conscious choice to invest in cycling infrastructure in the 1960s and now has high rates of cycling.

While decisions about transport infrastructure may be made for a variety of non-health reasons, our study provides further evidence that health needs to be integrated into decisions that are made about transport.

Oliver Mytton, Clinical Lecturer in Public Health, ̽��ֱ�� of Cambridge and Jenna Panter, Senior Research Associate, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

Is it time to ditch the car and find a more active way of getting to work? It could save your life, say Oliver Mytton and Jenna Panter from the MRC Epidemiology Unit, writing for ̽��ֱ��Conversation.

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Opinion: Surprising ways to beat anxiety and become mentally strong – according to science

cjb250 — Mon, 26 Jun 2017 10:44:20 +0000

Do you have anxiety? Have you tried just about everything to get over it, but it just keeps coming back? Perhaps you thought you had got over it, only for the symptoms to return with a vengeance? Whatever your circumstances, science can help you to beat anxiety for good.

Anxiety can present as fear, restlessness, an inability to focus at work or school, finding it hard to fall or stay asleep at night, or getting easily irritated. In social situations, it can make it hard to talk to others; you might feel like you’re constantly being judged, or have symptoms such as stuttering, sweating, blushing or an upset stomach.

It can appear out of the blue as a panic attack, when sudden spikes of anxiety make you feel like you’re about to have a heart attack, go mad or lose control. Or it can be present all the time, as in generalised anxiety disorder, when diffuse and pervasive worry consumes you and you look to the future with dread.

Most people experience it at some point, but if anxiety starts interfering with your life, sleep, ability to form relationships, or productivity at work or school, you might have an anxiety disorder. Research shows that if it’s left untreated, anxiety can lead to depression, early death and suicide. And while it can indeed lead to such serious health consequences, the medication that is prescribed to treat anxiety doesn’t often work in the long-term. Symptoms often return and you’re back where you started.

How science can help

̽��ֱ��way you cope or handle things in life has a direct impact on how much anxiety you experience – tweak the way you’re coping, therefore, and you can lower your anxiety levels. Here are some of the top coping skills that have emerged from our study at the ̽��ֱ�� of Cambridge, which will be presented at the 30th European Congress of Neuropsychopharmacology in Paris, and other scientific research.

Do you feel like your life is out of control? Do you find it hard to make decisions – or get things started? Well, one way to overcome indecision or get going on that new project is to “do it badly”.

This may sound strange, but the writer and poet GK Chesterton said that: “Anything worth doing is worth doing badly.” And he had a point. ̽��ֱ��reason this works so well is that it speeds up your decision-making process and catapults you straight into action. Otherwise, you could spend hours deciding how you should do something or what you should do, which can be very time-consuming and stressful.

People often want to do something “perfectly” or to wait for the “perfect time” before starting. But this can lead to procrastination, long delays or even prevent us from doing it at all. And that causes stress – and anxiety.

Instead, why not just start by “doing it badly” and without worrying about how it’s going to turn out. This will not only make it much easier to begin, but you’ll also find that you’re completing tasks much more quickly than before. More often than not, you’ll also discover that you’re not doing it that badly after all – even if you are, you can always fine tune it later.

Using “do it badly” as a motto gives you the courage to try new things, adds a little fun to everything, and stops you worrying too much about the outcome. It’s about doing it badly today and improving as you go. Ultimately, it’s about liberation.

Just jump right in … ̽��ֱ��National Guard via flickr, CC BY

Forgive yourself and ‘wait to worry’

Are you particularly critical of yourself and the blunders you make? Well, imagine if you had a friend who constantly pointed out everything that was wrong with you and your life. You’d probably want to get rid of them right away.

But people with anxiety often do this to themselves so frequently that they don’t even realise it anymore. They’re just not kind to themselves.

So perhaps it’s time to change and start forgiving ourselves for the mistakes we make. If you feel like you’ve embarrassed yourself in a situation, don’t criticise yourself – simply realise that you have this impulse to blame yourself, then drop the negative thought and redirect your attention back to the task at hand or whatever you were doing.

Another effective strategy is to “wait to worry”. If something went wrong and you feel compelled to worry (because you think you screwed up), don’t do this immediately. Instead, postpone your worry – set aside 10 minutes each day during which you can worry about anything.

If you do this, you’ll find that you won’t perceive the situation which triggered the initial anxiety to be as bothersome or worrisome when you come back to it later. And our thoughts actually decay very quickly if we don’t feed them with energy.

Find purpose in life by helping others

It’s also worth considering how much of your day is spent with someone else in mind? If it’s very little or none at all, then you’re at a high risk of poor mental health. Regardless of how much we work or the amount of money we make, we can’t be truly happy until we know that someone else needs us and depends on our productivity or love.

This doesn’t mean that we need people’s praise, but doing something with someone else in mind takes the spotlight off of us (and our anxieties and worries) and places it onto others – and how we can make a difference to them.

Being connected to people has regularly been shown to be one of the most potent buffers against poor mental health. ̽��ֱ��neurologist Viktor Frankl wrote: "For people who think there’s nothing to live for, nothing more to expect from life … the question is getting these people to realise that life is still expecting something from them."

Knowing that someone else needs you makes it easier to endure the toughest times. You’ll know the “why” for your existence and will be able to bear almost any “how”.

So how can you make yourself important in someone else’s life? It could be as simple as taking care of a child or elderly parent, volunteering, or finishing work that might benefit future generations. Even if these people never realise what you’ve done for them, it doesn’t matter because you will know. And this will make you realise the uniqueness and importance of your life.

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Most people experience anxiety at some point in their lives, but for some it can be a crippling condition. Writing for ̽��ֱ��Conversation, Olivia Remes, a PhD candidate at the Cambridge Institute of Public Health, looks at what science tells us about beating the disorder.

Micheal Saisi

Anxiety centred

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Opinion: Dairy got the all-clear this week - but was it justified?

cjb250 — Wed, 17 May 2017 08:55:43 +0000

A new study, published recently in the European Journal of Epidemiology, appeared to give dairy products a clean bill of health. ̽��ֱ��researchers found no evidence for an increased risk of cardiovascular disease or death from consuming dairy products – even full-fat dairy products.

These findings were widely covered in the media – headlines mostly singled out cheese, saying it does not increase the risk of heart attack or stroke. Some of the reports claimed that saturated fats do not increase the risk of cardiovascular disease, but the study didn’t examine saturated fat consumption itself.

It’s worth taking a closer look at the science behind the headlines.

Key findings

This new study is a type of study known as a meta-analysis because it pools data from earlier studies and analyses the combined data. In this instance, there were 29 studies that the researchers felt were of sufficiently high quality to include in their analysis. There were 783,989 participants in all, with an average age of 57 years. Each of the studies had asked healthy people about their usual diet and then followed them up over five to 25 years. Over the course of the follow up, 93,158 participants died (from any cause), 28,419 developed coronary heart disease and 25,416 developed cardiovascular disease (heart attack and stroke).

̽��ֱ��international team of researchers who conducted the meta-analysis found no statistically significant link between any of total dairy consumption (high- and low-fat combined), high-fat dairy consumption, low-fat dairy consumption, and risk of death, risk of coronary heart disease or risk of cardiovascular disease.

Among individual dairy products, milk consumption was not associated with cardiovascular disease or death, and neither was yoghurt consumption. For cheese and fermented dairy products (including sour milk products, cheese or yoghurt), there was a minor reduction in the risk of cardiovascular disease, but it seemed to be because of one large study. When this study – which showed an extreme result – was removed from the analysis, the link disappeared.

Strengths and weaknesses

Although not new, this research included the largest sample of participants to date on this topic and investigated both total and individual types of dairy products. ̽��ֱ��researchers applied sound meta-analysis methods and were careful to use extra analyses (called sensitivity analyses) to check their initial findings. However, there are some limitations of the individual studies, and meta-analysis, which are worth mentioning.

Although up to 29 studies were identified for the meta-analysis, the actual number available for each analysis was considerably less than 29. For example, for high-fat there were five studies for looking at death, nine for heart disease and seven for cardiovascular disease. And for yoghurt consumption, there were only three studies. This can compromise the confidence we can place in some of the results. For example, we can’t be certain that the association of yoghurt intake with cardiovascular disease is indeed null, as fermented dairy products – especially yoghurt – have been associated with reductions in cardiovascular risk, weight gain and type 2 diabetes in other research.

Another weakness is that the meta-analysis combined data from observational studies. Observational studies are not as robust as clinical trials. But this is a common limitation of studies of diet as it’s often not possible to keep people under close scrutiny – as required in clinical trials – for many years while comparing one type of diet with another.

With observational studies, there is always a risk that some other factor – one not being investigated – is the actual reason for the observed associations. To get around this, researchers take “confounding factors” into account when analysing the data. In this instance, the studies took into account such factors to very different degrees – some only including a very limited number of factors such as age, sex, smoking, or social status (such as education), while there are also other important factors such as obesity, physical activity, alcohol intake, ethnicity and other foods consumed that were missed in some studies. It is possible such health and lifestyle factors not taken into account by the researchers may have influenced the results.

Inconsistency in the definitions of groups of dairy products might also obscure interpretation. For example, some studies might include full-fat yoghurt in high-fat dairy products, whereas other studies might include both types of yoghurt in low-fat dairy products. Some dairy products such as cream and butter were not individually assessed in the meta-analysis.

Wider context

There is emerging evidence from other research, that not all foods that are rich in saturated fats have the same impact on health. This is probably because foods rich in saturated fat also contain many other ingredients. For instance processed red meat is associated with an increased risk of type 2 diabetes, whereas
dairy products, particularly yoghurt, are associated with a decrease in risk of type 2 diabetes, as we have also shown in two studies (EPIC InterAct and EPIC-Norfolk).

Most dietary research relies on people reporting their dietary habits, and this can be prone to error and inaccuracies, which can mask the detection of links between diet and health. Our own research has shown that measuring biomarkers of food intake in blood or urine can open up new possibilities for understanding links with disease and bypass errors due to self-reporting in questionnaires.

New evidence suggests that saturated fat in dairy may not be as bad for us as we once thought, but there isn’t enough evidence, just yet, to change dietary guidelines which, in the UK, recommend that saturated fats should make up fewer than 11% of all calories consumed from food.

Eirini Trichia, PhD student, MRC Epidemiology Unit, ̽��ֱ�� of Cambridge and Nita Forouhi, Programme Leader, MRC Epidemiology Unit, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

When it comes to health claims around the food we eat, it’s worth taking a closer look at the science behind the headlines, say Eirini Trichia and Professor Nita Forouhi from the MRC Epidemiology Unit, writing for ̽��ֱ��Conversation.

Jules Morgan

Cheese

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Opinion: How epigenetics may help us slow down the ageing clock

cjb250 — Fri, 12 May 2017 09:03:57 +0000

Humankind has a longstanding obsession with eternal youth. Stories about elixirs of life and fountains that quench one’s thirst for immortality have stirred our imagination since time immemorial. Different versions of these myths appear on every continent – even Alexander the Great’s conquests are sometimes attributed to his search for a restorative river that could heal the devastation of time.

Yet despite our obsession with ageing, we still know very little about how it works. Why and how do we age? Why does everyone seem to age differently? Can we slow it down? Should we? Luckily, we now have more precise tools than mythology to investigate these questions and we have invented an instrument that can predict ageing in mice based on the activity within their genome over time – and it may even be used to slow it down.

Ageing in humans and animals is inevitable but it happens differently across species and even between different organs in the body. But we do not yet know whether the way we age is predetermined, part of an inherent biological programme, or whether is it just down to wear and tear.

Biologists distinguish between two types of age: biological age, a measure of how well your body functions, and chronological age, which expresses how old you are. For example, a young person who drinks vast amounts of alcohol might have a very old liver. Worryingly, a young person with a very healthy lifestyle might also have a very old liver. It is still unclear what factors affect biological age and how.

But epigenetics, the study of how environmental factors and lifestyle choices influence our genes, is helping to shed some extra light on the issue. In particular, “DNA methylation”, a mechanism used by cells to control gene expression – whether (and when) a gene is turned on or off. DNA methylation entails fixing a gene in the “off” position via the addition of methyl groups to a DNA molecule. Essentially, as we age, DNA methylation modifies the function of genes without changing their underlying DNA sequence.

Epigenetic clocks

̽��ֱ��“epigenetic clock” is a tool for predicting both biological and chronological ageing and understanding the ageing process. ̽��ֱ��clock maps activity within a genome over time, based on DNA methylation levels at different sites.

Measuring the level of DNA methylation at certain sites on the genome can be used to estimate the biological age of a cell, tissue or organ. By comparing this age with chronological age and probing the differences, scientists can begin to understand how ageing works. They can also identify factors that influence the speed of the process, and find links with cancer, obesity, Alzheimer’s disease and many other conditions.

Steve Horvath published the most well-known example of an epigenetic clock in a 2013 paper. He analysed previously collected data by researchers who had studied methylation in both healthy and diseased human tissue, including in cancer. He then used it to chart how age affects DNA methylation levels throughout life. In doing that Horvath managed to identify 353 markers that are present throughout the body and change with age. ̽��ֱ��clock has wide applicability: it uses the same markers, irrespective of the DNA source within the organism, so you can use samples from any tissue or fluid in the body to predict biological age, with a respectable median error of 3.6 years.

One of the burning questions about Horvath’s epigenetic clock is whether it would be possible to make subtle changes to its molecular components (the methyl groups) and observe how these changes slow down or speed up ageing. Of course, such an experiment would be impossible in humans, for both ethical and practical reasons.

Experiment in mice

To address this challenge, our team of researchers from the Babraham Institute and the European Bioinformatics Institute in Cambridge, UK, proposed a new epigenetic clock, published in Genome Biology – the first ever such tool for studying ageing in mice.

Slowing down ageing in mice would be a giant leap in our quest for immortality. Rama/wikipeid, CC BY-SA

Computational methods and software for understanding biological data (bioinformatics) are critical for addressing this question and allowed us to create an accurate model of biological age. We can compare the predictions from the mouse clock to other epigenetic clocks, and draw conclusions about how mammals age. Our paper shows that changes in DNA methylation at 329 sites in the mouse genome can predict its age with an accuracy of just over three weeks.

We have validated our method by demonstrating that lifestyle changes known to shorten lifespan, for example removing the ovaries, did in fact speed up the mouse epigenetic clock. A high-fat diet, which we know is detrimental to human health, also accelerated the clock.

̽��ֱ��next step is to delve into the inner workings of the mouse epigenetic clock and change its ticking rate. For example we could identify molecules or drugs that alter the methylation clock and then change these by genome editing or drug treatment. This should reveal whether ageing is directly influenced by DNA methylation patterns, or if ageing is a read-out of a story already written in our genomes.

We will also be exploring new approaches to rewinding the ageing clock in order to rejuvenate cells, tissues or even whole organisms. So the old quest continues, but in the quieter realms of data analysis rather than expeditions to new shores. We hope one day to look back on epigenetics as the field that changed the game, and shed light on the ageless mystery of ageing.

Wolf Reik, Professor of Epigenetics at the Department of Physiology, Development and Neuroscience, ̽��ֱ�� of Cambridge and Oliver Stegle, Research Group Leader of Statistical Genomics, European Bioinformatics Institute

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Why do we age when we get older? Epigenetics may hold the answer – but could it one day help us turn back the clock? Professor Wolf Reik from the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge and Dr Oliver Stegle from the European Bioinformatics Institute look at the ‘epigenetic clock’ in ̽��ֱ��Conversation.

Pedro Ribeiro Simões

Older woman profile

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Opinion: How ‘frugal innovation’ can fight off inequality

cjb250 — Wed, 19 Apr 2017 13:59:25 +0000

Inequality is the defining social, political and economic phenomenon of our time. Just 1% of the world’s population now holds over 35% of all private wealth, more than the bottom 95% combined. Bad as this may seem, trends suggest that the situation will only get worse. Addressing it will involve multiple strategies working together, but one which is less well understood is how simple, affordable solutions to people’s problems can make a genuine difference from the bottom up.

One way of measuring inequality is known as the Gini coefficient. It gives us a useful and straightforward number between zero and one, where zero represents perfect equality where everyone has the same income, and one expresses the maximum of inequality. In the countries which make up the Organisation for Economic Cooperation and Development (OECD) the Gini was at 0.28 in the mid-1980s, but increased by 10% to 0.31 by the late 2000s.

Inequality is a global problem. In the form of absolute poverty, it exists across countries. About 4 billion people – more than half the world’s population – live on less than US$9 a day. But inequality is also a problem within countries. By the late 2000s, income inequality measured by Gini had risen in 17 out of the 22 OECD countries – in Finland, Germany, Israel, New Zealand, Sweden and the US, it increased by more than 4%.

̽��ֱ��cold, hard truth of inequality. ̽��ֱ��Hamster Factor/Flickr, CC BY-NC-ND

Making demands

Inequality is also a problem that exists on both the demand and supply sides of the economy. On the demand side: large numbers of people are excluded from the fruits of the economic process as they lack access to basic healthcare, education, nutritious food, and clean energy. This is largely an emerging world problem, but it is also increasingly a problem in the developed world.

On the supply side, large numbers of people are excluded from the economic process because they are shut out of employment in high-value-adding industries which rely heavily on skills and technology. This is largely a problem in the developed world where globalisation and tech have hollowed out manufacturing, but it is a problem in some developing countries too.

My work over the last decade leads me to believe that an important part of the battle against inequality lies in what could be termed frugal innovation. Simply put, it is about applying human ingenuity to create faster, better and cheaper solutions for more people in core areas such as financial services, health, education and energy. We can call it “frugal” because this is not about massive state-level or corporate investment, but it is about developing and delivering affordable technologies and ideas to meet basic needs at scale. This has the potential to address both supply and demand side aspects of inequality.

On the demand side, developing these frugal solutions across sectors promises to include large numbers of people currently without access to affordable financial services, education, and healthcare. Indeed, such a frugal revolution is already taking place in emerging markets in South Asia, Africa and Latin America. In India, such solutions in healthcare are bringing free or highly affordable services to large numbers of people in areas as diverse as cataract and heart surgery and prosthetics. Across the country, Devi Shetty has applied medical and management principles to reduce the cost of heart surgery to US$1,200 while maintaining global quality standards. He wants to get the price down to US$800.

Mobile payments in Kenya. WorldRemit Comms/Flickr, CC BY-NC-SA

In Africa, an earlier telecoms revolution is now driving a second generation of frugal solutions in key sectors such as financial services. M-Pesa, an SMS-enabled service that enables unbanked people to send and receive money though their mobile phones, has empowered over 25m Kenyans (many of whom have small businesses) to improve productivity and gain access to revenue-generating opportunities. Such mobile based payments are in turn driving affordable market solutions in areas such as solar lighting for those living beyond the reach of the electricity grid.

Similar frugal solutions in clean cookstoves, medical devices, transport, pharmaceuticals, sanitation, and consumer electronics are positioned to drive growth in Asia and Africa over the next few decades, helping to raise millions out of absolute poverty in the process.

Job makers

On the supply side, frugal innovation offers the possibility of generating more high value adding employment for more people, particularly in Western economies. Big corporations are increasingly lean and no longer hire the large numbers of people they did in the past. And so entrepreneurship is more than ever a key driver of growth, both in terms of output as well as in generating employment. Young people entering the workforce can no longer expect to be job takers; increasingly, they are expected to be job makers.

Luckily, they are now more empowered to do so: small teams of people can set up new companies and achieve scale in ways that weren’t possible before.

New tech for old problems. Keith Kissel/Flickr, CC BY

Technologies such as cheap computers, sensors, smartphones, and 3D printers are enabling such teams to invent and prototype in ways that were only available to large corporations or government labs in the past. This in turn has given rise to the maker movement where budding inventors can tinker in Make Spaces and Fab Labs with other like-minded people and develop solutions to problems they face in their communities. Ideas that have come out of Tech Shops and Make Spaces include the Embrace Baby Warmer and Simprints, a biometric device to manage medical records in the field in developing countries.

If these “makers” wish to commercialise their solutions, they can crowdfund the capital needed, outsource the manufacturing, list their products on amazon.com to help with distribution and use social media to spread the word. Indeed, such “maker spaces” could well morph into the high tech, local, sustainable factories of the future, delivering high value adding, creative manufacturing opportunities to cities where 20th-century polluting manufacturing has been systematically weakened over the last few decades, and where lost jobs in those sectors have sharpened inequality.

While most politicians and policy makers fulminate and flounder in their attempt to deal with rising inequality worldwide, a quiet frugal revolution is already addressing the problem right before their eyes. ̽��ֱ��state need not be a bystander. Now is the time for governments to sit up, take notice and spur this revolution on. Doing so could help save their societies and economies before it is too late.

This article has been co-published with the World Economic Forum.

Jaideep Prabhu, Director, Centre for India & Global Business, Cambridge Judge Business School

This article was originally published on ̽��ֱ��Conversation. Read the original article.

With inequalities set to get worse, it’s time to take radical action, says Jaideep Prabhu, Director of Centre for India & Global Business, Cambridge Judge Business School, writing for ̽��ֱ��Conversation. Could the answer lie in the ‘frugal revolution’ that is already under way?

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