Informatics for health – an interdisciplinary extravaganza.

A few weeks ago I attended the European Federation for Medical Informatics and the Farr Institute of Health Informatics Research’s Manchester-based conference – Informatics for Health 2017. The conference was a vibrant mix of academic thought topped off with a generous helping of public collaboration, showing that the field of health and medical informatics takes collaboration and public involvement very seriously.

Since health informatics covers all aspects of health-data collection, storage and processing it would be impossible to do justice to the sheer breadth of research presented at this conference in a single article. Therefore, here I will focus on a couple of my personal highlights.

On Tuesday the 25th, Susan Michie from University College London gave a keynote talk about the Human Behavioural Change Project:

With environmental, social and health concerns appearing endemic in our society, Suzan noted that one of the best ways to address these issues would be through targeted behavioural change interventions. These take a huge array of forms from subtle nudges implemented by many governments and large organisations (encouraging everything from litter reduction to targeted urinal use – see here for examples), to less than subtle public health campaigns. These interventions are widely documented across academic literature and show a range of outcomes and successes. Susan outlined a vision where this literature could be used to answer the big question:

‘What behaviour change interventions work, how well, for whom, in what setting, for what behaviours and why’

This is undoubtedly a pretty ambitious question to answer and it is made harder by the fact that the literature on this subject, although vast, is often fragmented, inconsistent and sometimes incomplete. So how do Susan’s team propose to tackle this big data problem?

The Human Behaviour-Change Project, funded by the Wellcome Trust, draws together some of the best minds in behavioural, computer and information science. Their output will depend on the close working relationships and interplay between all disciplines involved.

Behaviour scientists have been tasked with developing an ‘ontology’, basically a standardised method of categorising different behavioural change interventions. It is then hoped that this standardised ontology can be used to both sort existing literature and as a template on which new studies can be based. It is hoped that this will add some much needed order to the current fragmented literature and pave the way for further analysis. Specifically, computer scientists on this team will use Natural Language Processing (a branch of computer science which employs artificial intelligence and computational linguistics to sort and process large bodies of text) to extract and organise information from these studies, whilst also learning as they process this information.

Finally information scientists, the big data miners, will develop effective user interfaces which allow researchers to delve into this data and to untangle it in a way that reveals answers to many important research questions.

This is undoubtedly a huge task but with the combined input of so many specialists it certainly seems tractable.

On Wednesday the 26th the conference was drawn to a close with a compelling talk from Sally Okun, Vice President for Advocacy, Policy and Patient Safety at PatientsLikeMe, an online patient powered research network. The PatientsLikeMe network partners with 500,000+ patients living with 2700+ conditions and offers a platform for patients to share experiences and where researchers can learn more about treatments directly from those undergoing them. Indeed, more than 90 peer reviewed papers have already stemmed from data collected through the PatientsLikeMe network.

The theory behind this work is compelling and almost begs the question as to why such networks are not yet commonplace. Indeed, it’s no secret that online marketers spend billions analysing our search histories and purchase data in an attempt to feed us highly personalised targeted marketing, so why shouldn’t patient experiences be used to tailor personalised medicine? Although there are undoubtedly greater complications linked to the use of patient data, not to mention the perils of misinformation, this is no excuse not to try and work towards a digital ideal.

Sally also discussed the launch of their new platform, the Digital Me. This platform will combine a plethora of personal health data including genetic data, medical histories, activity tracking – basically if you can collect it you can include it. Their hope is that this data can be used to personalise medical treatments, tailoring them to your own individual requirements. Indeed, advances in statistical methods could take us beyond blanket prescribing and into a world where your digital profile can be compared to those similar to you (similarity being based on a large number of patient characteristics) and recommendations made based on successes and failure of treatments for you nearest digital neighbours (those sharing most of your traits).

As my first experience of an informatics-based conference, I was struck by both the breadth and depth of knowledge in the field and the ethos of working together to optimise our outputs – a skill which is often found lacking in other fields. It was also plain that researchers in this area value patient input and many elements of this conference were tailored to be accessible and engaging for a lay audience. Indeed, representatives from HeRC’s own patient public forum who attended the event enjoyed the opportunity to engage further with researchers and learn about engagement and involvement work being conducted across the field.

Post by: Sarah Fox

Save

Save

Vets, pets, data sets and beyond.

From the 10th to the 14th of April 2017 researchers from the UK’s flagship project on companion animal surveillance, the Small Animal Veterinary Surveillance Network (SAVSNET), set up shop at Edinburgh’s international science festival.

SAVSNET* uses big data to survey animal disease across the UK and ultimately aims to improve animal care through identification of trends in diseases observed by veterinary practitioners.

This work offers huge benefits for companion animals, meaning that interventions can be targeted towards those most at risk and risk factors for disease can be identified across the population.

There is also significant crossover between this work and that of human health data science. Indeed, lessons learned from the processing and analysis of big data from vets may be used to inform aspects of human data analysis while work on shared and zoonotic diseases, antibacterial use and resistance also offer significant benefit to human health.

So, for this week, we took our science to the public to engage, inspire, raise awareness and stimulate discussion about our work.

SAVSNET mascots Alan, Phil and PJ

The SAVSNET Liverpool team worked hard to develop a wide range of activities designed to bring data science to life and to raise awareness of their work while Dr Sarah Fox, from HeRC’s PPI team joined the fun to expand discussions beyond pets and into the realms of human health.

Our stall was designed to take the public on a data journey, a journey which began with our resident mascots Alan, Phil and PJ, who were suffering from a parasitic problem. Hidden in our fluffy friend’s fur were a host of unwanted passengers – ticks (not the real thing but small sticky models we used to represent real ticks). Visitors helped us to remove these pests from our mascots and learned that every time this process is performed by a vet, a medical record is created for that procedure. Indeed, vets across the country are regularly called upon to remove such pests and, assuming the practice is signed-up to the SAVSNET system, information on these procedures is transferred to data scientists.

The next stage of our data journey is one health researchers are very familiar with but which may remain a mystery amongst the general public – sorting and analysing these records.

Interactive sticker-wall showing seasonal tick prevalence.

Our stall was equipped with a large touch-screen PC, linked to the SAVSNET database and programmed to pull out and de-identify all vet records which made reference to the word tick. It was explained that, in order to perform a complete analysis of the prevalence of ticks across the UK, data scientists needed to manually sort through these selected records and confirm the presence or absence of a tick at the time of the recorded consultation. Now visitors to our stall could take part in their own citizen science project as they helped us to sort through these records, uncovering ticks and adding their findings to our maps of regional and seasonal tick prevalence. Dogs came up trumps as the pet most likely to visit their local vet to have ticks removed, while the ticks themselves seemed to indiscriminately pop up all around the UK (even in the centre of London) while also having a preference for outings during the warmer summer months.

In the final stage of our data journey, visitors had the chance to get hands-on with some data science theory.

A few beautifully coloured ticks alongside our wooded data blocks.

Dr Alan Radford, a reader in infection biology from the University of Liverpool, developed a novel way of exploring sample theory and odds ratios using wooden building blocks.

This activity consisted of hundreds of wooden blocks sporting either cat or dog stickers, a subsection of which also housed a smaller tick sticker (on their rear). Visitors were told that these blocks represented all the information available on cats and dogs in the UK. After conceding that they would not be able to count all of these blocks independently, visitors were encouraged to form groups and choose a smaller sub-sample of ten blocks each. Visitors counted how many of their chosen ten blocks showed cat stickers and how many showed dog stickers. As a rule most groups of ten contained more dogs than cats – since overall there were more dog blocks in the total population. However, inevitably we also saw variability and some individuals chose more cat blocks than dogs. This tactile and visual example of sample theory allowed a discussion regarding sample bias and how increasing the number or size of samples taken would bring you closer to the correct population value. Finally visitors were asked to turn their blocks around and count how many of their dogs and cats also had ticks. In our example cats were more likely to house a resident parasite but, with fewer cats to sample from, this was not always immediately obvious. Specifically, assuming a visitor chose 7 dog blocks and 3 cat blocks then found that 4 of their dogs had ticks while only two of their cats did, they might be forgiven for thinking that within our sample dogs were more prone to ticks. However, from this data our older visitors were taught how to calculate an odds ratio, which could show that our cats were actually more likely to house ticks than dogs. It was also noted that similar calculations are often used to calculate risk in medical studies and that it is often these vales which are reported in the media.

The view down our microscope of our preserved pests.

Alongside our data blocks, younger visitors also had the chance to get up close and personal with real life ticks, through both a colouring exercise and by peeking down our microscope at a range of preserved specimens.

Finally, we discussed how tick data and similar veterinary information could be used to improve the health of companion animals and to better understand disease outbreaks across the country. It was at this point we also introduced the idea that similar methods could also be applied to human health data in order to streamline and improve our healthcare services. Our discussions centred around the successes already shown in The Farr Institute for Health Informatics’ 100 Ways case studies and HeRC’s work, including improvements in surgical practice and regional health improvements from HeRC’s Born in Bradford study – whilst also engaging in a frank discussion around data privacy and research transparency. Visitors were encouraged to document their views on these uses of big data on our post-it note wall, garnering comments to the questions: “What do you think of big data?” and “Should we use human data?” A majority of visitors chose to comment on our second question, generally expressing positive feelings concerning this topic but, with many also noting the need for tight data privacy controls. Comments of note include:

Should we use human data?
Yes, but with controls and limited personal info
We need to get better at persuading people to change behaviour and ask the right questions to collect the right data.
Yes, it’s towards a good cause and can help people.
Using data is a good idea if it helps to make people better.
Yes, as long as there are sufficient controls in place.
Yes, but don’t sell it.
Yes, if you are careful not to breach privacy.

The data detectives.

Overall we had a great time at the festival and hope everyone who visited out stall took away a little bit of our enthusiasm and a bit more knowledge of health data science.

* co-funded by the BBSRC and in collaboration with the British Small Animal Veterinary Association (BSAVA) and the University of Liverpool.

Post by: Sarah Fox

Save

Save

Save

To share or not to share: delving into health data research.

In January this year I made a bold move, well at least bold for someone who is often accused of being painfully risk averse. I waved a fond farewell to life in the lab to take on a new role where I have been able to combine my training as a researcher with my passion for science engagement. In this role I work closely with health researchers and the public, building the scaffolding needed for the two to work together and co-produce research which may improve healthcare for millions of patients across the UK. The group I work alongside are collectively known as the Health eResearch Centre (part of the world-leading Farr Institute for Health Informatics) and are proud in their mission of using de-identified electronic patient data* to improve public health.

For me, taking on this role has felt particularly poignant and has lead me to think deeply about the implications and risks of sharing such personal information. This is because, like many of you, my health records contain details which I’m scared to share with a wider audience. So, with this in mind, I want to invite you inside my head to explore the reasons why I believe that, despite my concerns, sharing such data with researchers is crucial for the future of public health and the NHS.

It’s no secret that any information stored in a digital form is at risk from security breaches, theft or damage and that this risk increases when information is shared. But, it’s also important to recognise that these risks can be significantly reduced if the correct structures are put in place to protect this information. Not only this but, when weighing up these risks, I also think that it is immensely important to know the benefits sharing data can provide.

With this in mind, I was really impressed that, within the first few weeks of starting this role, I was expected to complete some very thorough data security training (which, considering I won’t actually be working directly with patient data almost seemed like overkill). I was also introduced to the catchily titled ISO 27001 which, if my understanding is correct, certifies that an organisation is running a ‘gold standard’ framework of policies and procedures for data protection – this being something we as a group hope to obtain before the year is out. This all left me with the distinct feeling that security is a major concern for our group and that it is considered to be of paramount importance to our work. I also learned about data governance within the NHS and how each NHS organisation has an assigned data guardian who is tasked with protecting the confidentiality of patient and service-user information. So, I’m quite sure information security is taken exceedingly seriously at every step of the data sharing chain.

But what will the public gain from sharing their health data?

We all know that, in this cyber age, most of us have quite an extensive digital-data footprint. It’s no accident that my Facebook feed is peppered with pictures of sad dogs encouraging me to donate money to animal charities while Google proudly presents me with adverts for ‘Geek gear’ and fantasy inspired jewellery. I don’t make too much effort to ensure that my internet searches are private, so marketers probably see me as easy prey. This type of data mining happens all the time, with little benefit to you or me and, although we may install add blocking software, few of us make a considered effort to stop this from happening. Health data, on the other hand, is not only shared in a measured and secure manner but could offer enormous benefits to the UK’s health service and to us as individual patients.

Our NHS is being placed under increasing financial strain, with the added pressure of providing care to a growing, ageing population with complex health needs. Meaning that it has never been more important to find innovative ways of streamlining and improving our care system. This is where health data researchers can offer a helping hand. Work using patient data can identify ‘at risk’ populations, allowing health workers to target interventions at these groups before they develop health problems. New drugs and surgical procedures can also be monitored to ensure better outcomes and fewer complications.

And this is already happening across the UK – the Farr Institute are currently putting together a list of 100 projects which have already improved patient health – you can find these here. Also, in 2014 the #datasaveslives campaign was launched. This highlights the positive impact health-data research is having in the UK by building a digital library of this work – type #datasaveslives into Google and explore this library or join the conversation on twitter.

One example is work on a procedure to unblock arteries and improve outcomes for patients suffering from coronary heart disease:

In the UK this procedure is carried out in one of two ways: Stents (a special type of scaffolding used to open up arteries and improve blood flow) can be inserted either through a patient’s leg (the transfemoral route) or via the wrist (the transradial route). Insertion through the wrist is a more modern technique which is believed to be safer and less invasive – however both methods are routinely performed across the UK.
Farr institute researchers working between The University of Manchester’s Health eResearch Centre and Keele University used de-identified health records (with all personal information removed) to analyse the outcomes of 448,853 surgical stent insertion procedures across the UK between 2005 and 2012.

This study allowed researchers to calculate, for the first time, the true benefits of the transradial method. They showed that between 2005 and 2012 the use of transradial surgery increased from 14% in 2005 to 58% in 2012 – a change which is thought to have saved an estimated 450 lives. They also discovered that the South East of England had the lowest uptake of surgery via the wrist.

This work shows one example of how research use of existing health records can highlight ways of improving patient care across the country – thanks to this research the transradial route is now the dominant surgical practice adopted across the UK (leading to an estimated 30% reduction in the risk of mortality in high risk patients undergoing this procedure).

Reading through all these studies and imagining the potential for future research does convince me that, even with my concerns, the benefits of sharing my data far outweigh the risks. But, I also recognise that it is of tantamount importance for patients and the public to be aware of how this process works and to play an active role in shaping research. It seems that when the public have the opportunity to question health data scientists and are fully informed about policy and privacy many feel comfortable with sharing their data. This proves that we need to strive towards transparency and to keep an active dialogue with the public to ensure we are really addressing their needs and concerns.

This is an amazingly complex and interesting field of study, combining policy, academic research, public priority setting and oodles of engagement and involvement – so I hope over the next year to be publishing more posts covering aspects of this work in more detail.

Post by: Sarah Fox

*The kind of data which is routinely collected during doctor and hospital appointments but with all personal identifiable information removed.

 

Save

Afforestation Vs reforestation

It is well known that deforestation is an increasing global problem. Even those with little scientific background are bombarded with information through social media, specifically regarding consequences of deforestation including global warming. Indeed, many charities, schools and individuals are now taking a stand and doing all they can to tackle this problem.

The planting of trees can be divided into two categories: afforestation and reforestation. Reforestation refers to planting trees on land that was previously forest whereas afforestation refers to planting trees on patches of land which were not previously covered in forest. The general idea behind both is: as many trees as possible, wherever possible.
However, ecology is a complex science. Are we focusing too much on carbon sequestration and not enough on the planets ecosystems as a whole? Are some ecosystems being neglected and forgotten? Perhaps. This article will cover some issues associated with afforestation and reforestation.

Reforestation is beneficial when trees have been previously removed. However, these new trees will never create exactly the same ecosystem as the original forest. Indeed, the original trees which were cleared may have been hundreds, even thousands of years old meaning that it may take many years for the new trees to catch up. In addition to this, rare species lost during the original deforestation may not be replaced, meaning extinction and a reduction of biodiversity could be inevitable.

Tropical grassy Biome

Afforestation can also have negative consequences especially if the tree planters don’t consider the environment they are introducing the new trees into. The idea of afforestation is to plant trees on patches of unused, degrading land. However, land which may appear degraded may actually house its own ecosystem, for example a Savanna or tropical grassy biome. Research has suggested that tropical grassy biomes are often misunderstood and neglected. These ecosystems can provide important ecological services. In addition to this, these ecosystems could contain rare species, which could be outcompeted by the introduction of new trees.Therefore, although carbon sequestration will increase, many ecosystems will be negatively affected or lost.

It has to be noted that both reforestation and afforestation can be advantageous when tackling global warming. However, possible negative impacts must also be taken into account in order to protect the planet as a whole. This can be achieved by ensuring that deforestation is kept to a minimum and afforestation only occurs on truly degraded land. There is desperate need for more research into areas of land before trees are planted upon them. The biggest challenge today is education. Charities, schools and individuals need to be made aware of this before it’s too late. Without awareness, irreversible damage can occur unknowingly. Effective conservation work requires more than just planning trees at random and this needs to be taken considered on a global scale.
If we don’t stand up for all of our precious ecosystems, who will?

Post by: Alice Brown

References:
http://www4.ncsu.edu/~wahoffma/publications/pdf/Parr2014TREE_TropicalGrassyBiomes_MisunderstoodNeglectedAndUnderThreat.pdf
https://pixabay.com/en/photos/plain/?cat=nature

 

Save

Save

Can I please buy one of your kidneys?

Should we legalise the sale of human organs?

In the UK alone the average waiting time for a kidney transplant is 3 years, this costs the NHS around £24,000 per patient per year and in 2013 – 2014 1000 people died whilst on the transplant waiting list. Dialysis patients also often say they feel that they are just existing rather than living. But, if these patients could get a transplant from a living donor, their life expectancy would increase up to 23 years and their lives could really begin. With increasing cuts to the NHS budget is it possible that the cost-effectiveness of kidney transplant might persuade the government to legalise a market in human organs?  The implementation of a legal organ market would also increase the human organ supply and eliminate the consequences of the black market.

Due to a shortage in organs, the black market and transplant tourism is thriving. Annually, 15,000 – 20,000 illegal kidney transplants take place around the world, often in developing countries such as India and the Philippines. There are even slums in the Philippines dubbed “kidney-vile”, as the majority of the slum’s residents have been driven to sell a kidney. But the black market is built on systematic deception. Brokers coerce desperate workers to sell a kidney then give them much less money than they were promised. Nor do they care about the surgical quality and often leave donors with little or no aftercare. Consequently, donors often become ill and are unable to continue their usual hard labour, which perpetuates their poverty, rather than alleviating it. Recipients are also affected by black market fraud: often these kidneys are not screened properly and donors are coerced to cheat their medical records. As a result of these schemes and poor hygiene standards, recipients often contract diseases such as hepatitis B/C and HIV.

Group of men from Baseco “Kidney-ville” in Philippines, displaying their scars from selling a kidney.
Group of men from Baseco “Kidney-ville” in Philippines, displaying their scars from selling a kidney.

Iran is currently the only country with a compensated and regulated kidney donation program. In this system, there are no brokers and it is charity organizations that coordinates donors with recipients. The government pay a fixed price for organs and cover the costs of all necessary aftercare for donors. Due to this system, Iran is currently the only country with no kidney transplant waiting list. It has also successfully eliminated its black market, and has still maintained a respectable percentage of altruistic donations. Nevertheless there are flaws to the Iranian system as discussed here.

Erin & Harris proposed an ethical, highly regulated, system in which only individuals within a nation are eligible to sell or receive organs. The market would have one purchaser (e.g. the NHS in the UK) and organs would be allocated fairly, giving recipients an equal chance of receiving a transplant regardless of their economic background. This system would also remove the draw for brokers, and subsequently reduce the exploitation of vulnerable people. Medical screening would ensure only healthy individuals could sell an organ, which would to minimise risk (Gill & Sade, 2002). Such a system would also provide proper medical care for donors who would also benefit from a full psychological evaluation, to make sure they are aware of the consequences of their actions.

A study of 478 donors from the Iranian regulated system has shown their health did not deteriorate after the sale, and that 90% of them were content with selling their kidney. These results contrast markedly with the study of 305 Indian donors in an unregulated market. The health of 90% of these donors declined, people living below the poverty line rose up to 20% and 79% of donors would not recommend selling a kidney. This shows that within a regulated program, both vendors and patients are better cared for and are more satisfied with the transplant process.

The strongest argument against the sale of organ is the possible exploitation of the poor. Critics argue that legalisation could lead to a market that would exploit poorer people, as they might view organ sale as a last resort. But, is it exploitation if a person makes a reasoned decision to take an action they consider to be the best option to improve their life? One can’t assume that money would simply overrule a person’s judgment. A black market would also lead to greater exploitation than any legalised market ever would. Prohibiting an organ market is paradoxical, to restrict an individual’s autonomy and cause moral harms to liberty.

Another prominent argument against the sale of human organs is that it would lead to commodification of the human and therefore corrupt human dignity. Commodification is an unsuitable term to use for the sale of a kidney, since there are numerous other circumstances when paying money does not insinuate loss of dignity, such as surrogacy.The scarcity of organs and, death and exploitation of people will not be resolved through rhetoric of moral repugnancy and human dignity.

Under prohibition, patients are suffering and dying whilst waiting for a transplant. Both vendors and recipients are exploited by the black market, and the human rights of poor people are violated. These problems will continue to exist as long as there is a dearth of organs. So, should a market in human organs from living persons be legalised? Or is it merely a naive and impractical idea, only appropriate for a dystopian future. Either way, the possibility of legalising a regulated and ethical market should be explored.

Post by: Alyssa Vongapai


References

Erin, C. A., & Harris, J. (2003). An ethical market in human organs. Journal of Medical Ethics , 29 (3), 137–138.

Ghods, A. J. (2009). Ethical issues and living unrelated donor kidney transplantation. Iranian Journal of Kidney Diseases , 3 (4), 183–191.

Goyal, M. (2002). Economic and Health Consequences of Selling a Kidney in India. Journal of the American Medical Association , 288 (13), 1589.

Higgins, R., West, N., Fletcher, S., Stein, A., Lam, F., & Kashi, H. (2003). Kidney transplantation in patients travelling from the UK to India or Pakistan. Nephrology Dialysis Transplantation , 18 (4), 851–852.

Hippen, B. E. (2005). In defense of a regulated market in kidneys from living vendors. The Journal of Medicine and Philosophy , 30 (6), 593–626.

Kidney Org. (2010). Transplantation Cost Effectiveness. [Online] Available from:http://www.kidney.org.uk/archives/news-archive-2/campaigns-transplantation-trans-cost-effect/. [Accessed on 5 Aug 2016]

MacKellar, C. (2014). Human Organ Markets and Inherent Human Dignity. The New Bioethics: A Multidisciplinary Journal of Biotechnology and the Body , 20 (1), 53–71.

Moazam, F. (2009). Conversations with Kidney Vendors in Pakistan. Hastings Center Report, (June), 29–44.

New Internationalist. (2014). Human traffic: exposing the brutal organ trade. [Online] Available
from:http://newint.org/features/2014/05/01/organ-trafficking-keynote/. [Accessed on 5 Aug 2016]

Organ Donation. (2015). Transplant save lives. [Online] Available from:http://www.organdonation.nhs.uk/newsroom/fact_sheets/transplants_save_lives.asp.
[Accessed on 5 Aug 2016]

Pat Roque. (1999). Group of men from Baseco “Kidney-ville” in Philippines, displaying their scars from selling a kidney [Photograph]. At: https://digital.newint.com.au/issues/88/articles/1890. [Accessed on 5 Aug 2016]

The Wall Street Journal. (2015). Cash for kidneys: The case for a Market for organs. [Online] Available from:http://www.wsj.com/articles/SB10001424052702304149404579322560004817176.
[Accessed on 5 Aug 2016]

World Socialist Web Site. (2015). Dramatic increase in worldwide illegal organ trade. [Online]
Available from:http://www.wsws.org/en/articles/2012/07/orga-j14.html. [Accessed on 5 Aug 2016]

Save

Insight from behind the lab bench: Could a period pain treatment be re-purposed to treat Alzheimer’s disease?

Today we are lucky enough to have the opportunity to publish a post written by Mike Daniels – one of the researchers behind the recent discovery that a drug used for the treatment of period pain may have a role to play in the treatment of Alzheimer’s disease. We hope you enjoy the opportunity to slip behind the lab bench and see what happens behind the scenes of a big scientific discovery.

My name is Mike Daniels, I am a PhD student working at the University of Manchester. We’ve just published a paper in the journal Nature Communications on how currently available drugs may be used to treat Alzheimer’s disease. The Brain Bank North West got in touch with us and gave us a fantastic opportunity to add our voice to the current media storm surrounding this research. I hope I can give you a detailed look at the ins and outs of this important research and offer some insight into the workings of a big research project.

Screen Shot 2016-08-19 at 20.48.07Our lab group are particularly interested in AD, not just because it affects over 26 million people worldwide without any truly effective treatment but also because our speciality is immunology and research suggests that an overactive immune system may play an important role in AD. One particular part of that immune system recently implicated in AD is something called an inflammasome. The inflammasome is a large bundle of proteins which forms a kind of machine within cells whose job it is to produce proinflammatory cytokines. These cytokines go on to promote inflammation in the brain which can worsen AD.

What’s particularly exciting for us is that this inflammasome appears to be largely redundant in everyday immune functions like fighting bacteria or viruses. This means we should be able to inhibit it in patients without rendering them susceptible to infection.

OK so we have a plan – inhibit the inflammasome complex in the hope of improving outcomes for people living with AD. But how do we do this? We could design new drugs (something our lab is involved in right now) but the process of getting a new drug from bench to clinic can take around 20 years and cost around 1.6 billion dollars. Another quicker, cheaper option is to do something called ‘repurposing’, this basically means taking a drug already approved and on the market and using it to treat a different disease. With this in mind our lab head Dr. David Brough decided to test a number of drugs from a large class called non-steroidal anti-inflammatory drugs (NSAIDs) to see if they could inhibit the inflammasome and thus potentially be used in AD. So, this was the project I was tasked with in my first week of PhD life nearly two years ago.

We began by testing a number of these NSAIDs on immune cells cultured in a petri dish. This gave us the important opportunity to screen a large number of drugs without unnecessary use of animals. When we ran these screens we had a bit of a surprise. The more famous NSAIDs such as ibuprofen (Nurofen) had no effect. However, one drug, mefenamic acid, was able to inhibit the inflammasome and prevent release of inflammatory cytokines in the cells. Mefenamic acid is only available by prescription and is prescribed largely to treat period pain.

So, how does mefenamic acid inhibit the inflammasome?

Research suggests that ion channels on the cell surface play an important role in inflammasome activation and that mefenamic acid may inhibit some types of ion channels. To better understand this we formed a collaboration with a London-based research group led by Dr. Claudia Eder – an expert in electrophysiology (researching ion channels). It was with the help of Dr. Eder’s lab that we identified the target of the drugs as a chloride channel called the volume-regulated anion channel (VRAC).

Screen Shot 2016-08-19 at 20.56.56Now we had the drug and the mechanism but we still don’t know whether this drug would be effective in treating AD. This is where we needed to look at the drugs action in a living system. The first model system we chose was a rat model of amyloid-beta induced memory deficits. Build-up of amyloid-beta is a thought to be a major factor in memory impairment and AD. Indeed, if injected into the brain of rats, amyloid-beta causes permanent memory deficits. As part of a collaboration with Dr. Mike Harte’s lab here at Manchester, we injected a group of rats with either mefenamic acid or a placebo and found that those which received the drug were completely protected from amyloid induced memory deficits.

We then moved to look at the effect of the drug in a genetic mouse model of AD. These mice had been altered to express some of the same genes found in humans with the genetic form of AD and, like human sufferers, these mice develop memory deficits with advancing age. When treated with mefenamic acid at the age of onset, these mice did not develop memory deficits, unlike animals treated with a placebo. We also found that the brains of placebo mice displayed signs of intense inflammation while those of drug treated mice remained completely normal.

So to conclude, AD is a terrible and currently incurable disease which we believe to be partially caused by an overactive immune system – specifically over-activity of a protein complex called an inflammasome. We found that the commercially available drug mefenamic acid was able to inhibit the inflammasome and reduce memory loss in both mouse and rat models of Alzheimer’s-like memory deficits.

But what’s the next step? We are hoping to begin to move mefenamic acid into clinical trials to see if it could really work in humans. Luckily, because the drug is already known and approved we can skip the safety testing stage of the clinical trial process. Unfortunately however, clinical trials remain extremely expensive and, as mefenamic is off patent and can no longer be sold for profit, gaining funding through pharmaceutical companies is nigh-on impossible. This means we are relying on grants from fantastic charities such as Alzheimer’s Society and Alzheimer’s Research UK in order to move this study forward.

A lot of work is needed and it will still be a while before we have results in people currently living with AD, but this remains an exciting step and we can only hope that it will go some way to treating this horrible disease.

Guest post by: Mike Daniels

Screen Shot 2016-08-19 at 20.25.13Mike is currently studying for a PhD in neuroinflammation at the the University of Manchester, UK. His work is based mainly on the role of a huge protein complex called the inflammasome in diseases such as Alzheimer’s, stroke and haemorrhagic fever. When he’s not in the lab he’s usually found up a mountain or out in the countryside somewhere and is always on the lookout for any new science outreach ideas!

The Human Sensor: Making the Invisible Visible

Breathe. Breathe deeply. Breathe in, breathe out. With each breath in, breathe in peace, tranquillity and calm. With each breath out, release tension, anxiety and pain. Let your mind be still, and your body relax, with an ever-present focus on your breath.

Such words and ideas may sound very familiar, and take you to a place of calm. Or they might sound completely foreign and a flight of fancy. The truth is, precious few of us in our daily lives ever consider our breathing outside of an escapist yoga class. But how many fewer of us, when we think about our breathing, take a moment to consider what might be in the air that we are breathing, and how that might be affecting us?

Air pollution is without doubt one of the biggest problems faced by the world’s cities. As estimated by the World Health Organisation, air pollution exposure causes 7 million premature deaths each year – one in eight of all global deaths. Whilst a significant number of these deaths occur in China (where there are estimated 4,000 premature deaths each day caused by air pollution) and India (where the non-smoking populace has a 30% lower lung capacity), Europe isn’t nearly as clean as it could be. A report from the EU’s European Environment Agency (EEA) says pollution is now the single largest environmental health risk in Europe, responsible for more than 430,000 premature deaths.

Closer to home, the picture remains grim. Manchester is the second most polluted city in the UK, and one of the most polluted cities in Europe. In Greater Manchester, the annual mortality estimate is over 1,000. But what actually are the pollutants that are causing all this damage?

One of the most significant is PM 2.5 , which is particulate matter condensed in air with a diameter smaller than 2.5μm (mainly sulphates, nitrates and carbon). These are nasty mixtures of combustion particles, metals and sulphates, and at less than 5% the diameter of a human hair, they can penetrate deep into the lungs. They have been linked to heart disease and lung cancer, and cause an estimated 29,000 premature deaths in the UK.

In addition, nitrogen compounds such as Nitrogen Dioxide (NO 2 ) form from the combustion process in vehicles. Long term exposure to NO 2 reduces lung capacity and lowers resistance to respiratory infection. The UK fails to meet the EU air quality standards for this pollutant, and exposure to NO 2 results in an estimated 23,500 premature deaths across the country.

According to the World Health Organisation, air pollution is the biggest public health problem faced by the developed world. But as we walk through busy streets, we never consider these effects. Apart from the odd stench of fumes from a bus or a lorry that we might notice, the fine particulates are undetectable to our senses and invisible to us. The cold statistics and hard science don’t relate to our daily experience. If we perhaps were more actively aware of how serious a problem this is, we might feel more inclined to drive less, or take more walks in the park, or simply avoid the busy streets. So how can we be more acutely aware of the science in our daily lives?

One way of connecting ourselves to certain issues and facts is through art. Music, dance and painting have all deeply emotionally resonated with us for millennia, in ways which science cannot. So scientific, socially conscious art could pave the way forward.

Screen Shot 2016-07-22 at 23.02.54In collaboration with Manchester European City of Science, the non-profit organisation Invisible Dust have commissioned the artist Kasia Molga to create a show in the streets of Manchester that brings this issue out into the open. Called the ‘Human Sensor’, dancers will wear futuristic suits that light up in different colours depending on what they are breathing, making tangible the effects of poor air quality.

These live performances take place across the 23rd-29th July, with the launch at 7:30pm on no.70 Oxford Road (formerly the Cornerhouse). Invisible Dust are also hosting an information space there, open from 23–29 July, 1–5pm weekends and 1–9pm weekdays with free drop-in talks and workshops every day.

If you want to bring yourself into the present, become more aware of your surroundings and the world around you, then focus on your breathing. But remember there is more to the world around us than what we see.

Guest post by: Carl Thomas

Learn more about the project here:

invisible dust

Human Sensor

 

Save

Save

The Case of the Jumping Carbons

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish our winning article written by Tilly Hancock from Oswestry School:

Screen Shot 2016-06-19 at 19.09.50

Imagine you are inside a nuclear reactor, a UK design. Not only are you inside it, but you are part of it; a carbon atom inside the graphite core which houses the control rods and fuel rods (the ‘moderator’). Around you the environment is glowing with heat and radiation, all given off in the splitting (fission) of uranium-235 nuclei. The temperature of 450°C is no problem, and you remain tightly bound in a lattice arrangement with your fellow carbons.

However, when the uranium nuclei split, they spit out more neutrons which pelt towards you at high speeds. One slams into you, and you slow it down, as is your job, so it travels at a suitable speed to cause more fission events. In this process you absorb the neutron’s energy, and get knocked out of your slot in the lattice. You whiz towards your fellow carbon atoms, knocking more out of their spaces like a billiard ball, wreaking havoc in the strict order of the graphite crystal. Eventually you transfer all of your extra energy to your neighbours and come to rest, filling a vacancy left by another displaced carbon or squeezing in between the orderly lattice layers (as an ‘interstitial’). Here you wait, ready to absorb the excess energy of the next neutron. The upheaval is routine to you, as during your life in the reactor you may switch places up to 30 times.

This is just one atom, but what are the consequences of millions jumping around like this?

Screen Shot 2016-06-07 at 16.46.44
A finite element model of a graphite sample and how the model behaves when irradiated or heated. Image credit: Dr Graham Hall. Manchester University

Well, the effects are unpredictable. The radiation barrage that the graphite endures can cause it to change its material properties; its thermal expansion, strength and even its dimensions, in strange ways. Even to the human eye, these changes would be noticeable. The moderator can change shape by up to 2%, depending on the grade of graphite; a surface that started smooth may finish rough. The dimensions may warp so that the control rods used to restrain the nuclear reaction may no longer fit into their channels. It is clearly important to completely understand how the graphite will change when designing new reactors or maintaining the existing ones. The problem is that we don’t.

For years, the only way to investigate the effects of the jumping carbon atoms has been using ‘materials test reactors’, which can take over 3 years and £10 million to complete a single experiment.

Is there an easier way to predict what the carbons’ dance can lead to?

Like in so many fields, computers are now proving their worth. Manchester University’s Dr Graham Hall designs models which do part of the test reactors’ job. He imagines how those millions of carbon atoms move around and uses similar previous models to predict some of the complex property changes. What’s more, to model a lump of graphite in a reactor-like environment, just one week would be expended, as opposed to those three years required by the test reactors. Although these models are unlikely to be used to design new reactors, they are tackling the problem of the variability between different grades of graphite.

Screen Shot 2016-06-06 at 13.44.03
The irradiation-induced dimensional changes of graphite at two irradiation temperatures predicted from finite element models compared with the experimental data. Image and data courtesy Dr Graham Hall, Manchester University.

Comparing computer predictions to experimental data has helped researchers advance their understanding of what those carbon atoms really get up to inside the reactors and more importantly, how this affects the moderator as a whole. Hopefully, one day soon only minimal usage of materials test reactors will be needed, to calibrate models like this one, sparing millions of pounds and many, many years, but for now the jumping carbon atoms will continue to keep researchers on their toes.

Post by: Tilly Hancock – courtesy of Sarah Fox (Volunteer with the British Science Association)

For more amazing scientific articles please visit our friends at Things We Don’t KnowThings We Don’t Know is a not-for-profit organisation that seeks to explain the cutting edge questions scientists are trying to solve, in everyday language.

Save

Shedding Light on the Nucleus

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish one of our runner up articles written by Hayley Martin from Oswestry School

“The nucleus can be thought of like an engine of a car – driving the actions of the cell”. This is an analogy made by Professor Dean Jackson at Manchester University. With a passion for the genome and forty years of research behind him Professor Jackson has become an expert in understanding mammalian nuclei and chromosomes and how the organisation of their structures defines the cell’s behaviour. In order for these cells to function correctly the genetic code stored in the DNA of each gene has to be interpreted by a process called gene expression, where information from the gene is used in the synthesis of the gene product. These gene products often include proteins such as enzymes, hormones and antibodies, all vital to our survival. Gene expression is immensely complicated due to the number of processes involved. Professor Jackson has been studying these processes and has helped to shed light on exactly why this expression is so complicated.

Figure 1 – The nucleus of a human cell – showing the distribution of DNA (blue), the transcription factories (green) and proteins (red) involved in further modification of RNA.
Figure 1 – The nucleus of a human cell – showing the distribution of DNA (blue), the transcription factories (green) and proteins (red) involved in further modification of RNA.

Transcription is the first process that contributes to gene expression – it is the process whereby information from DNA is copied and made into a new strand of RNA which goes on to synthesize proteins. Professor Jackson has been able to tag newly formed RNA with a fluorescent antibody that can be detected using a laser scanning confocal microscope. This equipment scans a beam of a specific wavelength of light through the specimen, causing the antibodies to fluoresce. The resulting image is displayed in Figure 1. Images such as this have allowed him to locate the areas in the nucleus where this RNA is formed – he refers to these areas as “transcription factories”. He has also found that these factories are made up of many other genes and proteins which assemble into specific complexes. Such knowledge is key to defining the required level of synthesis of each gene product. It also provides the potential for co-regulation of genes in that the way that one gene in this complex is expressed will affect the expression of another gene. Recent work has concluded that genes can have as many as 20 other genetic elements, known as enhancers, that contribute to the gene’s overall expression, which is why it is so complex.

Gene therapy is an exciting modern concept: It offers the prospect of improving lives without the need for drugs with potential side effects and offers possibilities for treating diseases that previously had limited therapeutic options. So far it has been considered as an approach to replacing mutated genes with normal functioning copies, inactivating or removing damaged genes and introducing a new gene that might help the body fight off a disease. With the use of new techniques such as ‘CRISPR’ gene insertion is relatively easy. However Professor Jackson’s research has highlighted how gene therapy isn’t as simple as just inserting a gene – it has to be controlled in the right way by these complex processes in order for the cell to have control of its actions. The difficulty in controlling these actions means that gene therapy is currently a risky process and is not a common treatment. Trials are underway to develop effective gene therapy methods of treating inherited disorders including haemophilia, cystic fibrosis and viral infections such as HIV. We can hope, with advances in the understanding of nuclear structure and processes of gene expression, that safe and effective gene therapy treatments will become a reality.

Post by: Hayley Martin – courtesy of Sarah Fox (Volunteer with the British Science Association)

Can the Onset of Psychosis Be Predicted by the Presence of Neuro-inflammation?

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish one of our runner up articles written by Maaham Saleem from Withington Girls’ School:

Imagine a life where the dawn of each new day is accompanied by severe hallucinations, delusions and an inability to respond to stimuli in a way that is deemed ‘normal’. Where the problems that you face heavily impair your ability to carry out social interactions, and leave you in a debilitated state. This life is reality for patient with psychosis, a mental health problem that causes people to perceive and interpret events differently from the average human mind. Psychosis can occur in a number of different conditions such as schizophrenia and bipolar disorder.

5147733588_e263f2b3f5_z
During recent times, a great deal of interest has arisen within the scientific community regarding the link between this condition and inflammation in the brain. In the late 20th century, post-mortem studies in patients with schizophrenia showed the presence of inflammation. However, these results were not always consistent, possibly due to differences in the regions of the brains which were examined. However, more recent studies, using brain scans in living patients, did find a more consistent increase in microglial activation in patients with psychosis, which is an indicator of neuro-inflammation. Microglia are resident, innate immune cells in the brain which have long been connected with the pathology of neurodegenerative diseases. The activation of these cells indicates inflammation, and it was suggested that individuals that display such inflammation may have a pre-disposition to developing psychotic disorders later in life.

At the Wolfson Molecular Imaging Centre of the University of Manchester, researchers are investigating whether this link between neuro-inflammation and psychosis does indeed exist. In order to ensure that the conclusions are valid, a large amount of evidence must be generated to support it and so a study is conducted in collaboration with other centres around the country. In this study, three groups of volunteers are tested; patients who have had psychosis for many years, patients for whom the onset of psychosis is recent, and healthy volunteers to act as controls. Each of these groups consists of twenty patients, therefore a total sample size of sixty patients is used in order to increase the statistical power of the results and increase the likelihood that they are representative of the majority of patients with psychosis.

3576501997_c519a2bfa4_z
All volunteers undergo a brain-scan called Positron Emission Tomography, or PET scan. PET scans involve the injection of a radioactive tracer into the body which emits positrons as it decays inside the tissues. This radiation can be detected by cameras. By using a specific radioactive tracer called [11C]PK11195, microglial activation can be measured in order to determine the amount of inflammation in the brain. Many of the results from studies to investigate this link between neuro-inflammation and psychosis seem to suggest that neuro-inflammation does indeed exist. Although of course more studies must be carried out in order to confirm this hypothesis, it does present an exciting new prospect of a possible treatment and establishment of preventative measures to assist patients with psychosis.

Post by: Maaham Saleem – courtesy of Sarah Fox (Volunteer with the British Science Association)