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Archive Emma Kampouraki

4 steps towards powerful research outputs

By Emma Kampouraki

Research has been constantly criticised in recent years. It seems rather odd that while increasing efforts have been made to upgrade the regulatory framework as well as the level of research, we are facing more than ever research outputs and publications of low quality or even results of trials that still remain unpublished. However, there are some simple steps that could improve the published research outputs.

1. Reducing publication bias
First and foremost, research results, positive or negative, should be published without reservation. I often hear early-career scientists complaining about being constantly rejected by journals for their negative results that lack significance. Rarely will I find a well-known researcher publishing studies that failed to prove the hypothesis. Whole books have indeed been written about the publication bias.
Equally, protocols that failed because of not easily predictable parameters should also be reported so that similar attempts are avoided. One reason for this is failure to critically assess the prior literature and another is the unspecified statistical assumptions in the analysis of studies. A statistician should be consulted to calculate sample sizes that are required for the target power of study and to set the relevant assumptions from the beginning.
Negative results and unsuccessful protocols should be seen as equally important and we should always allow them to influence our decisions to conduct further research based on previous failed attempts, the same way as positive results urge further study.

2. Maintaining transparency in research publishing
Peer-review is powerful precisely because it is made by peers; scientists that know how to recognise high-quality research and well documented research results. Most journals today publish work that has been peer-reviewed by at least two reviewers. Selecting a journal in which low quality studies with obvious pitfalls have been published is all but good practice.
Moreover, transparency is well maintained when study protocols and data analysis plans are published well in advance. These should be in accordance with the published results when the study is completed and any reasons for deviation from the initial plan should be well justified. Most researchers should be happy to make the complete set of data publicly available, for the purposes of not only transparency but also meta-analyses. Study funders should grant access to detailed clinical data in response to legitimate requests from both researchers and regulators. These data-sharing initiatives are increasing more and more lately and should be supported.

3. Clinical trial results
Randomised clinical trials are a special category, as they are considered the gold standard in biomedical research. In reality, not all questions are answered with a clinical trial that includes an intervention. Observational studies are very powerful especially when they are well designed and bias is reduced. It is required by law that all trial protocols are pre-published at clinicaltrials.gov. Other details such as recruitment goals, data analysis plan and sources of funding are recorded as well. Funders and researchers should stick to their commitment to publish the (positive or negative) results within a timeframe after completion to inform next steps that might already be in progress (e.g. research funding applications for similar study).

4. Systematic reviews
Last but not least, systematic reviews are an incredibly powerful tool to assess the quality of existing evidence and identify gaps in current knowledge. Every large trial should be supported by a systematic review that justify its planning and of course its cost. Otherwise, there is a great risk that the particular study may not add much to the problem and therefore it won’t be cost-effective. Systematic reviews should be reproducible, peer-reviewed and according to the Cochrane standards.

Each and every new generation of researchers should feel the responsibility to maintain the quality of research that the scientific community demands. It is now more essential than ever that we provide powerful and undoubtable evidence simply because we rely a lot on it to make informed decisions in clinical practice and patient management. We are all involved so we should care!

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Institute of Physics Lectures

This week the Institute of Physics North East Branch is putting on two free public events!

A Fortunate Universe – Life in a finely tuned cosmos Thursday, 19 October 2017, 19:00 – 20:00, James Duff Lecture Theatre (PH8), Physics Building, Durham University

Application of Computational Bioacoustics in Ecology and Agriculture Friday, 20 October 2017, 19:00 – 20:00, Hancock Museum, Barras Bridge, Newcastle upon Tyne NE2 4PT

Full details can be found here.

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Archive Justin Byrne

What use is a generalisation if the real world holds only individuals?

By Justin Byrne

In my PhD, I compare ancient British woodlands with younger ones in an effort to describe how microbial biodiversity, and the associated ecological processes, change over time. Scientific endeavours like this focus on building generalisations, but what is the use of a generalisation if, in the real world, things are always atypical?

Biodiversity, the breadth of variation in the living components of an environment, tends to increase over time. Below is a picture of some tanks of standing water in our office, initially these tanks were used to age water for our aquarium. When spring began, the water would quickly fill with algae so we stopped using it. Instead of throwing it away, we left it, occasionally topping it up with wastewater from aquarium water changes. When we put a few plants in there things really kicked off and now the tanks teem with life. Water boatmen, snails, water fleas and no doubt plenty of other microscopic inhabitants have colonised the tank. Nature is the same but slower.

In natural systems we generally expect environments to go through a series of successional stages. First, colonisers arrive, generally fast growing, with high dispersal and plenty of offspring. At a time it was popular to refer to these species as r-selected species (r for high growth rate). These reshape their environments with their activity, waste, and their death, providing altered environments for other species to colonise. As more species arrive, they continue to change their environment until long living species generally crowd out and dominate, forming a climax community. These, were once popularly referred to as k-selected species (k for Kapazitätsgrenze, the German word for carrying capacity – the stable population limit of the environment). This is succession, a conceptual model of how ecosystems behave. British woodlands are the basis of my work and have an extensive history of management, not unlike my water tanks. The Ancient British woodlands used in my research have not yet reached a climax community, the theorised final state of succession. They do not conform to the model. Perhaps the post-glacial wildwood reached climax over the thousands of years of succession it experienced before humans reshaped the British Isles.  Perhaps chaotic processes within it prevented it reaching that point. Despite having good generalisations about how the environment should shape itself, in reality things are more messy.

We base our models of how ecosystems work on imperfect individuals. I attempt to look past the individuality of woods with a carefully designed study with lots of replicates. Generally, I might find that the diversity of microbes in woodlands increases over time. Alternatively, “middle aged” woodlands might be most diverse. Statistics gives me an idea of how trustworthy this generalisation is. However, it remains impossible to say what a certain wood will be like in a few decades or centuries. Whatever relationships I find, individual woods may entirely buck the trend. The strength of scientific theories is in their ability to predict general trends. Their weakness will always be in predicting individual events.

Any understanding of the mechanisms behind observed results is going to be a generalisation, and for that we sacrifice certainty. I think that is why many have come to doubt the advice of experts; those who can tell you what should happen, but never what will happen. Developing scientists have to become comfortable with uncertainty, while striving to increase the confidence of their assertions. Offering assurance is not a natural part of this skill set, which can be troublesome when a scientist is called upon to explain an item of news or a development (see the ongoing climate debate). There are two clear responses to this; either science, being uncertain, is a poor arbiter of truth, or certainty is a western virtue that should be valued less highly. To see the downsides of each worldview, one need not look far.

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Newcastle University State of the Art Lectures

By Jess Leighton

The Newcastle University State of the Art Lectures kick off this week with Professor Louise Robinson, director of the Institute for Ageing. Starting this showcase of Newcastle’s real-life research impact with a medical field constantly expanding with new challenges seems only fitting.

“Live Better for Longer” is the Institute for Ageing’s ethos, and this is no small challenge. Mental and physical health are two obvious emphases for the team, but they are also working on the broader well-being of older people, including community independence and use of technology. As medicine advances and we live longer, there are many challenges which the Newcastle University Institute for Ageing aims to address; allowing these extra years to be spent independently and in the best health possible.

Ageing research is nothing new for Newcastle – the biggest and most developed ageing cohort study in the world was started here in 2006. The Newcastle 85+ study  followed up 1,000 older people and was ground-breaking in the field of ageing, exploring issues from sleep to genetics and diet to eyesight.

Professor Louise Robinson – who has led the unit to attract over £35million in research funding – comes from a Primary Care background, and champions community-based dementia care in particular. While the team explore issues from diagnosis to treatment, there is also a focus on high quality care for those who already have dementia. This research is very sensitive in involving a vulnerable group of patients – but absolutely key to high quality care as well as treatment.

Professor Robinson is speaking on Thursday 12th October from 3-4pm in the David Shaw Lecture Theatre, Newcastle Medical School, and all are welcome to hear more about the current research. More details about the Institute of Ageing’s work is available here.

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Archive Leonie Schittenhelm

From cats in boxes to pigeons who like art

By Leonie Schittenhelm

Hello and welcome back to another instalment of ‘Wacky scientific papers with Leonie’! With the winners of the Ig Nobel Prize for Improbable Research 2017 announced just over two weeks ago, it is not surprising that the internet is abuzz with the surprising, mind-blowing and just plain old weird contestants honoured this year. Each year these prestigious prizes are given to research that – in their own words – first makes people laugh and then makes them think. Here we collect some of this year’s winners and mix in some old favourites for good measure. Let us know your favourite funny paper in the comments!

1. ‘On the rheology of cats’ or can a cat be both a solid and a liquid?

 Rheology is a field that is primarily concerned with the flow of matter, both in liquid and solid state. The author of this paper, M.A. Fardin, charmingly argues that cats can behave in different ways depending on the surface they are lying on and the space they are trying to manoeuvre themselves into. His methodology? ‘1. Bring an empty box. 2. Wait.’

2. ‘Equations of the End: Teaching Mathematical Modeling Using the Zombie Apocalypse’

Modelling how quickly and widely infectious diseases can be transmitted is a complex mathematical undertaking but immensely valuable for disease management. But how can you teach these complex mathematical skills to students without scaring them off? Simple answer: Zombies!

3. ‘Pigeons can discriminate “good” and “bad” paintings by children’

A classic in the world of scientific questions no one has even thought of asking before. This study first asked adults to label children’s paintings as either ‘bad/ugly’ or ‘good/beautiful’ and then tried to teach the distinction to pigeons – with surprising successes! Pigeons can apparently learn what is considered beautiful to human eyes and use both colour and pattern of the paintings to come to their assessment.

4. ‘Shit happens (to be useful)! Use of Elephant Dung as Habitat by Amphibians’

While clearly important research, the title of this paper is more than cheeky! Even more admirable however is the type of experiments undertaken to yield this data: Ahimsa Campos-Arceiz examined no less than 290 (!) elephant dung piles to see if any amphibians had made their home in them. That’s research dedication right there.

5. ‘What happens if we don’t defend academic freedom’

More serious in tone, this paper was published to protest the increased legal pressures on international universities in general, and the Central European University in particular, that are pushed by an increasingly volatile Hungarian government. The paper itself is short, because what happens if we don’t defend academic freedom? ‘No abstract 1. No introduction 2. No argument and contribution 3. No analysis 4. No conclusion and avenues for future research 5. No more questions asked’.

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Archive Cassie Bakshani

The (Novice) Yogi’s Guide to Mental Wellbeing

By Cassie Bakshani

It’s easy to get bogged down and overwhelmed by life’s responsibilities and forget to take time to look after yourself; my previously fractious mental state and perpetual anxiety were a testament to this. I prioritised work intensely and neglected my interests, at the expense of my health and mental wellbeing. I took me a long time to realise that this lifestyle was entirely unsustainable and even then I wasn’t sure how to rectify it.

My first tentative step was scheduling time for myself, with the aim of reinvigorating old interests and acquiring new ones. That’s how I stumbled upon yoga. It looked like a fun class to do at the gym I’d just joined and two of my friends were keen to try it too. What I hadn’t anticipated was that beginning practising yoga would be a metaphorical (and actually, incidentally rather literal) sigh of relief for both my body and mind. A few sessions in and I was generally a bit less tense, ten sessions in and I was looking upon the week ahead with greater clarity and perspective. Nearly one year, one inversions class, 6427 handstand attempts and innumerable falling-on-face incidents later, I’m a different person mentally. I now do two taught sessions and three-four hours of independent practise weekly and I think it has opened me up to many of the restorative benefits yoga has to offer; it allows me to reflect, refocus, be consistently more productive and less irritable. I know some of you reading this may be a little concerned by the lack of solid evidence to back up those last statements, so let me provide some for you now.

It is well-known that meditative practices such as yoga facilitate the transition in the body from the sympathetic nervous system to the parasympathetic nervous system, i.e. from fight or flight mode to rest and digest mode. This is because focusing on and controlling breathing allows practitioners to achieve a state of deep relaxation and mental calm. Subsequently, the body reduces cortisol and catecholamine levels, including epinephrine/adrenaline and norepinephrine/noradrenaline, which trigger anxiety responses, such as increased heart rate and blood pressure. Moreover, a study published this year found that, when sustained for a period of 3 months or more, yoga stimulated production of brain-derived neurotrophic factor (BDNF). This protein supports growth, survival and plasticity of hippocampal and cortical neurons and is concurrently involved in mood regulation and promotion of stress resilience, therefore could play a significant role in cognitive restructuring in response to stress.

Convinced yet? Maybe not, but I definitely encourage you to at least give yoga a try. It may not necessarily change your life, but it could make your day, and your head, that little bit lighter.

Namaste.

Here are some great yoga events and classes/workshops taking place in the North East in the coming months:
https://www.eventbrite.co.uk/e/yogamatters-north-east-yoga-mala-tickets-36821561281?aff=es2

http://happyyoganewcastle.com/beginners-yoga/
http://www.yogalilies.co.uk/workshops/?options%5Bids%5D=489&options%5Bsite_id%5D=44972
http://www.yogalilies.co.uk/workshops/?options%5Bids%5D=496&options%5Bsite_id%5D=44972

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Archive Leonie Schittenhelm

Why should we care about rare diseases?

By Leonie Schittenhelm

The amount of common diseases we have yet to cure can seem overwhelming sometimes: no week without a looming ‘Alzheimer’s epidemic’ headline or an advert on the bus warning about the 1 in 3 chances of having a stroke. Surely all energy and research funds should be channeled into treating and healing these wide-spread diseases? Yes and no. While learning more about these diseases is incredibly important to help the people affected by them, researching less common diseases should not be forgotten.

A disease is considered rare if less than 5 people in 10,000 are affected by it. While relatively few other people will share the same disease, the amount of rare diseases ranges between 6,000 and 8,000. This means that over 30 million people in the European Union alone are estimated to suffer from these rare conditions, often without relevant therapeutic options and frequently misdiagnosed for years. To make matters worse, significant research results are difficult to obtain due to inherently small sample sizes and experts in a specific rare disease being equally scarce.

However, with the advances of genetic diagnostics, diagnosing rare diseases correctly and research to find better treatments is finally in reach. And while the problem of small local sample sizes persists, the European Union has pledged to fund collaborative projects tackling this problem as part of the Horizon 2020 programme. One such example is the RD-Connect network that is being built by Professor Hanns Lochmüller and his team at Newcastle University. The online platform collects a range of clinical and genomic data on rare diseases, while encouraging the researchers to use their resources to upload their own, building a huge database on rare diseases.

Understanding these diseases better does not only help the people affected by them, it can also increase our understanding of biochemical pathways in the general population. Because the majority of rare diseases are caused by a single gene mutation, symptoms can be usually traced back to the malfunction of a specific gene. This means that elucidating why a set of symptoms occurs can not only provide therapeutic options for patients, but also reveal the function of a specific gene in the healthy population.

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Archive Leonie Schittenhelm

Bright Club: how to see the humour in academia

By Leonie Schittenhelm

Sweaty hands. Knees buckling. An acute desire to run to the toilet, lock myself in a stall and not come out for the rest of the night. And those weren’t even all the signs of acute nervousness I felt minutes before going onto the stage to perform my first Bright Club set. Let’s pretend you are me, roughly a year ago, which is incidentally the amount of time it took me to take up all my courage and convince myself to actually do this. You might ask yourself questions such as: ‘What is a Bright Club?’ and ‘Why does it freak this poor person out so much?’. Easy enough to answer: Bright Club, often also dubbed the ‘thinking person’s variety night’, is a comedy night about science and everything academia. The clue is in the name, and that’s where my nervousness comes back in: the people on the stage, telling the jokes? That’s academics, who for one night only exchange their pipette for a microphone or their lecture theatre for a comedy club to tell some jokes about their work. And that night, it was my turn.

Let’s rewind a bit. Don’t get me wrong, I enjoy a good laugh just as much as the next person. But to actually get up on a stage and talk about things you thought were funny when you wrote them up at home? That seemed just completely inconceivable to me. I mean, how do you even find things that are funny about your work? Being a PhD student in my first year, the only way I could keep my impostor syndrome in check was by appearing as serious about my area of interest as possible. To make matters worse, in the weeks preceding Bright Club, my science just flat-out refused to work, full-stop. Suffice to say, I was not in a very good place to see the humour in my daily work. So when Elin Roberts and Marilena Pace at the Centre for Life sent us home to ‘just write down some ideas for your set’, I was stumped. Where should I even begin to look? But as I got on with experiments and meetings, my work started to transform in front of my eyes. Surely not everyone has conversations about blood in the lunch room? And am I the only one that kind of treats their cell cultures like pets to be nurtured and loved?

I think there are a lot of good reasons to do Bright Club. The relief you feel when the audience laughs at your first joke. The growing exhilaration after the second laugh, and every laugh thereafter. The boost in confidence after doing something that you never thought yourself capable of. The amazing support from the Centre for Life, which will take you by the hand to write your first comedy set and practice it with you until you are ready to shine. But for me personally, the ability to see the humour in my work has been the best and most long-lasting effect of doing Bright Club. Everyone knows PhDs are hard, but everything gets that much easier if you can have a good laugh about it.

Interested in taking part in the next Bright Club event on the 3rd of October at the Stand Comedy Club in Newcastle? Contact marilena.pace@life.org.uk fore more information and all the important dates for your diary.

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Archive Emma Kampouraki

In the era of pharmacogenetics

By Emma Kampouraki

Differences in the genetic material we carry make us who we are. Individual variability is important when prescribing drugs, as we can now genotype a person in less than a few hours. We can then use this information to inform drug prescription. Genotype-informed prescription is more than virtual reality nowadays. Both FDA (US Food and Drug Administration) and EMA (European Medicines Agency) recommend the use of genetic information to drive the decision of treatment and prevent patients from serious mistakes in the prescription of “useless” drugs. Although ethical concerns don’t facilitate the establishment of genotyping in clinical practice, it is common sense that it is also unethical not to use all the existing data for a more informed and safe process of drug therapy. Trial and error is still in place in most drug schemes, however moving on to a more individualised approach has the advantages of costing less and resulting in more effective treatments, increasing patient satisfaction and compliance at the same time.

The first FDA-approved genetically-guided therapy was for the treatment of HER2 (human epidermal growth factor) positive metastatic breast cancers in 1998. The case of trastuzumab (Herceptin®) paved the way for the co-development of gene-based therapies with tests to detect the drug targets, in order to identify the right therapies for the right patients. Simultaneously with the approval of trastuzumab, a laboratory technique for detection of HER2 protein overexpression in breast cancer cells (Dako North America, Inc. for HercepTest).

Later, the cases of olaparib (Lynparza®) and rucaparib (Rubraca®) prove the increasing need for more targeted therapies and the outstanding interest of medicines regulatory agencies to cover this need as soon as possible. Recent findings show that tumours rely on poly (ADP-ribose) polymerase (PARP)-mediated DNA repair for their survival. Both olaparib and rucaparib are inhibitors of the PARP enzymes responsible for DNA damage repair. In 2014, olaparib was the first drug in its category to be approved for ovarian cancer with mutations in BRCA gene, with only mild to moderate adverse effects to date. In fact, the clinical trial data that convinced the EMA in 2014 for the efficacy of olaparib were not as convincing for the FDA for various reasons. A few months later, olaparib was granted approval in the US. Further testing on humans confirmed the increased progression-free survival for patients with BRCA mutations on olaparib. Two years later, in 2016, rucaparib became the second drug with accelerated approval for treatment of patients with BRCA mutations. In addition, the need for a reliable genetic test to identify patients eligible to receive the treatment was also covered by the FDA. The FoundationFocus CDxBRCA test is the first FDA-approved next-generation sequencing (NGS)-based companion diagnostic, which detects alterations in BRCA genes in the tumour tissue of ovarian cancer patients.

Between the two decades of cancer treatment genotype-based approvals, the first oral anticoagulant warfarin, used for the prevention and treatment of strokes, thrombosis and atrial fibrillation among others, was shown to be influenced by genetic variation, as well. Genetic testing prior to prescription along with genotype-guided dosing of warfarin was recommended, changing the way we perceive drug dosing. Warfarin is one of the most commonly prescribed drugs, with more than 2 million people are treated with warfarin every year in the US, hence the importance of such advancement is great, as it affects the clinical management of millions of people worldwide.

The list of drugs that receive approval and are specifically designed for variant genotypic characteristics is fast growing. It is our responsibility to educate health professionals and most of all patients. Now, more than ever, we need to find the best way to use and protect genetic information, while at the same time proving its power to change clinical practice forever.

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Archive Leonie Schittenhelm

Text before you drink? – how mobile phones could help reduce binge drinking

By Leonie Schittenhelm

Everyone’s had those good intentions – that fitness app just after new years, this meditation app that the colleague that always seems like she has it all together recommended. The first few days go well, but then – well, let’s say the reminders keep popping up, without causing much more action than the thumb swipe that dismisses them. So how could text message-based intervention help people who have problems with binge-drinking? That is just what a collaborative study between Dundee, Glasgow, Edinburgh and Newcastle wants to find out.

Over 12 weeks they sent over 100 text messages to each study participant – the clue: instead of merely reminding them to drink less, they were designed to foster interaction and response. Questions such as ‘Can you think of any reasons why it might be a good idea to cut down a bit on your drinking?’ were interspersed with real quotes from pilot study participants (Mark from Edinburgh says: “Sometimes I’ve not had enough money to pay the bills.”) and challenges to identify achievable goals to reduce alcohol intake, if even just a little bit.

Responses ranged from humourous (On the question who would be pleased to see them drink less: “My wife, she’d get more money for shoes!!”) over heart-breaking (on the question, if they or their friends had experienced problems due to drinking: “I’ve had a friend that’s died because of drink. Fell off a balcony in a block of flats.”) to aspirational (“Stop earlier in the evening or at the very least slow down compared to others.”). While the researchers including Dr. Falko F. Sniehotta from Newcastle University, still note some caveats of the study, the success of actively engaging individuals in a text-based intervention programme instead of passively informing them speaks for itself. Answering one of the last messages one participant writes: “Had my ups and downs but I’m getting there now. Enjoyed the experience, thank you.”

If you want to have a look at the study yourself: Irvine, Linda, et al. (2017) “Real time monitoring of engagement with a text message intervention to reduce binge drinking among men living in socially disadvantaged areas of Scotland.”