Features

Many of the stories on Arts Blog focus on research in the arts and humanities, but what about the students who are taking their first steps into research? In a new series, we hear the stories of some of Oxford's brilliant students.

First up is Rachel Kowalski, who started a PhD in Irish history just a few weeks ago. Professor Karen O'Brien, Head of the Humanities Division, says Rachel's story 'shows how remarkable our Humanities doctoral students are'. 

'People often find their true passions later in life, but few have the courage to make sacrifices to pursue them. Since Rachel made the leap into academia, she has achieved so much in a short space of time, and she is a great role model for other people who are interested in learning later in life.'

Now over to Rachel...

Tell us a bit about your school education and why you didn’t enter higher education?

RK: I went to a very normal state school. The school was neither brilliant nor awful. I did reasonably well at school, and actually started a degree in History after my A Levels, but left after a couple of months because I felt utterly unprepared for higher education. I felt at a total loss when it came to using primary material, and was pretty poor at writing coherently.

What did you do after finishing school?

RK: After leaving my degree I got the first job I could within walking distance from my family home, because I was unable to afford to buy a car or pay to commute a long way to work. So I spent four years working for my local branch of Barclays Bank in roles including Cashier, Banking Hall Coordinator and finally as a Personal Banker. I enjoyed the role, but hated the sales pressure as I felt it led people to sell products irresponsibly in order to hit targets.

After this I managed to secure a job working for the University of Oxford in IT support for the Finance Team. I felt relieved to be out of sales, and for the first time found myself sufficiently stress free to reflect on what I wanted from life. I decided to take up studying again, part time at first, in order to achieve a degree. The plan was to spend my time as a student working out what career I wanted, and to use the degree I was setting out to obtain as a launch pad for change, for instance, by getting myself onto a graduate training scheme.

My part-time foundation certificate in Modern History, at Oxford University’s Department for Continuing Education gave me the necessary grounding in History, and confidence I needed to leave my full-time career in IT in order to finish my degree in just a further 2 years of full time study. I applied to a few institutions, but chose to accept my place of second year entry onto the History BA course at King's College London (KCL).

What made you decide to apply to KCL to study history at the age of 26? Was it a hard decision to make?

RK: My tutors at Continuing Education, Dr Christine Jackson and Professor Tom Buchanan, recommended Kings College London to me, when I failed my interview to get into Oxford to finish the degree full time. Whilst, as I have already said, the foundation certificate improved my writing and research skills, I was still lacking confidence in my own ability and so the interview scenario and the degree system which would have followed were not appropriate for me at the time.

My decision to leave my career, and plunge myself dramatically into debt, was a little daunting. But I felt it was worth the risk as the grades I was achieving on my foundation certificate were consistent. I am very much of the mindset that you only live once and should live the best life that you can. My education was my gift to myself, and has changed my life in ways I could never have imagined.

Do you think you worked harder as an older student than you would have done at 18?

RK: I absolutely am working harder now than I would have at 18. As a mature student I feel I have a stronger work ethic; developed through my time spent working in the private and public sectors. I also have a greater understanding of the ‘cost’ of my studies. By this I mean that I know what it will feel like to pay back to make monthly loan repayments when earning a salary. I also think my sense of pride and shame are more acute than at 18. I now quite simply could not hand in a piece of work I am not proud of. Whereas I think 18 year old Rachel just might have done.

Tell me a bit about the ‘breakthrough’ that led to your undergraduate thesis being published in a journal?

RK: The piece scored 84, and my supervisor, Professor Ian McBride [now the Carroll Professor of Irish History at Oxford University] suggested I revise it for publishing. Both he, and another academic Dr Huw Bennett, gave me feedback on the piece and helped me choose a suitable journal to apply to.

The piece was peer reviewed and accepted for publication with just minor amendments. So, really the breakthrough was simply having a supervisor who believed in me and encouraged me to push for something I never imagined would be possible for a piece of undergraduate work.

The most exciting thing about the speed with which the piece was published was the fact that I was able to footnote myself in my Masters dissertation.

What is your research proposal?

RK: I am researching the nature of the Provisional IRA campaign during the Northern Ireland ‘troubles’ between 1969 and 1979. My project will synthesise the findings of original quantitative and qualitative research in order to gain a deeper understanding of the organisations’ agenda, methods, accuracy and impact.

I am collecting new data on their daily activities, successful and unsuccessful, to disaggregate the campaign and understand the influences which shaped it. I will be considering their target discrimination policy primarily; determining who they deliberately targeted, as opposed to who was injured or died as a result of their actions.

I am learning to use GIS software to map the macro picture of my findings, and then will be moving onto conduct micro studies in a few disparate regions to establish snapshots of the PIRA’s activity and external influences in different times and places.

I will be drawing conclusions about the organisation, and extrapolating the findings to discuss the study of political violence and asymmetrical warfare more generally.

Are you working on any other projects at Oxford?

RK:I have founded a seminar series called ‘The Oxford Seminar for the Study of Violence’. It is an exciting interdisciplinary seminar series which runs fortnightly at Wolfson College. This year we are covering a wide range of topics. For instance, Dr Jelke Boesten is talking to us about Gender Based Violence in Peru; Dr David Skarbek is presenting a paper on the social mechanisms which reduce prison violence between gangs in the American prison system; and Dr Simon Prince is talking to us about the intimacy of violence in the early period of the Northern Ireland Troubles.

What do you want to do after you finish your PhD?

RK: I would very much like to stay in academia so will be looking for Post-Doctoral positions and eventually a full time academic job. It is a very competitive field, however, so am very open minded to other career paths such as research roles within my field, publishing, or teaching.

How are you financing your studies and why do you think is it important that students in the humanities have access to scholarships?

RK: I am very fortunate to have been awarded a full scholarship for my DPhil; The Wolfson Scholarship in the Humanities. The scholarship is awarded solely on the merit of the student and the quality of the research proposal submitted at application.

Scholarships are so very important in the humanities because quality research is by no means commensurate with the personal wealth of the researcher. Many students cannot afford to pursue higher education in the face of ever increasing university fees, yet alone the cost of living. Scholarships thus contribute to eroding the inequalities in our education system by supporting those who have succeeded academically regardless of whether they have received a private education, or have come from a privileged background.

I certainly would not be studying for a PhD if it were not for my scholarship. What is more, had my Wolfson scholarship not been so generous, I would not have had the time to launch my seminar series or dedicate myself fully to my studies. Rather, I would have had to resort to working part-time, as I have had to do all the way throughout my full-time undergraduate and Masters studies at Kings College London.

This post originally appeared on the Caltech website. Author: Lori Dajose.

Many infectious pathogens are difficult to treat because they develop into biofilms, layers of metabolically active but slowly growing bacteria embedded in a protective layer of slime, which are inherently more resistant to antibiotics. Now, a group of researchers at Caltech and the University of Oxford have made progress in the fight against biofilms. Led by Dianne Newman, the Gordon M. Binder/Amgen Professor of Biology and Geobiology, the group identified a protein that degrades and inhibits biofilms of Pseudomonas aeruginosa, the primary pathogen in cystic fibrosis (CF) infections.

The work is described in a paper in the journal Science.

'Pseudomonas aeruginosa causes chronic infections that are difficult to treat, such as those that inhabit burn wounds, diabetic ulcers, and the lungs of individuals living with cystic fibrosis,' Newman says. 'In part, the reason these infections are hard to treat is because P. aeruginosa enters a biofilm mode of growth in these contexts; biofilms tolerate conventional antibiotics much better than other modes of bacterial growth. Our research suggests a new approach to inhibiting P. aeruginosa biofilms.'

The group targeted pyocyanin, a small molecule produced by P. aeruginosa that produces a blue pigment. Pyocyanin has been used in the clinical identification of this strain for over a century, but several years ago the Newman group demonstrated that the molecule also supports biofilm growth, raising the possibility that its degradation might offer a new route to inhibit biofilm development.

To identify a factor that would selectively degrade pyocyanin, Kyle Costa, a postdoctoral scholar in biology and biological engineering, turned to a milligram of soil collected in the courtyard of the Beckman Institute on the Caltech campus. From the soil, he isolated another bacterium, Mycobacterium fortuitum, that produces a previously uncharacterised small protein called pyocyanin demethylase (PodA).

Adding PodA to growing cultures of P. aeruginosa, the team discovered, inhibits biofilm development.

'While there is precedent for the use of enzymes to treat bacterial infections, the novelty of this study lies in our observation that selectively degrading a small pigment that supports the biofilm lifestyle can inhibit biofilm expansion,' says Costa, the first author on the study. The work, Costa says, is relevant to anyone interested in manipulating microbial biofilms, which are common in natural, clinical, and industrial settings. 'There are many more pigment-producing bacteria out there in a wide variety of contexts, and our results pave the way for future studies to explore whether the targeted manipulation of analogous molecules made by different bacteria will have similar effects on other microbial populations.'

While it will take several years of experimentation to determine whether the laboratory findings can be translated to a clinical context, the work has promise for the utilisation of proteins like PodA to treat antibiotic-resistant biofilm infections, the researchers say.

'What is interesting about this result from an ecological perspective is that a potential new therapeutic approach comes from leveraging reactions catalysed by soil bacteria,' says Newman. 'These organisms likely co-evolved with the pathogen, and we may simply be harnessing strategies other microbes use to keep it in check in nature. The chemical dynamics between microorganisms are fascinating, and we have so much more to learn before we can best exploit them.'

The paper is titled 'Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.' In addition to Costa and Newman, other co-authors include Caltech graduate student Nathaniel Glasser and Professor Stuart Conway of the University of Oxford. The work was funded by the National Institutes of Health's National Institute of Allergy and Infectious Diseases, the National Science Foundation, the Howard Hughes Medical Institute, the Molecular Observatory at the Beckman Institute at Caltech, the Gordon and Betty Moore Foundation, and the Sanofi-Aventis Bioengineering Research Program at Caltech.

In a guest blog, Professor Peter McCulloch from the Nuffield Department of Surgical Sciences, explains the importance of randomised trials in deciding whether subsequent trials are necessary.

In medical science, as in all walks of life, we are impressed by dramatic effects.  If a new treatment seems much better than an old one initially, there is often impatience to get on and use it, and people question why one would want to conduct formal trials.

Doctors who feel this enthusiasm for what they see as a breakthrough often argue that it’s not ethical to do a randomised trial of an exciting new treatment, because the benefits seem so obvious, and randomisation means that half the patients are deprived of them. Of course breakthroughs sometimes turn out to be false dawns, but the idea that something might be so obviously better than what we have now that it doesn’t need a randomised trial is pretty widespread in medicine.

We decided to look at this by trying to find all the published randomised trials where the new treatment was reported as being five times better than the previous treatment (or a controlled group). We thought this ‘five times better’ idea might be a useful rule for medical science. If a hazard ratio of five (i.e. the new treatment is five times better) nearly always predicted correctly that subsequent trials would always report significant benefits, then we could use this as a signpost for the point where no further evidence is needed. Unfortunately, this turned out not to be true.

We studied all of the trials in the Cochrane Collaboration Database (more than 80,000) and found that there were very few instances where there had been both trial with a dramatic effect like this and a subsequent trial. We looked at the ones we found and unfortunately the ‘five times better’ rule was wrong in over one third of the cases.  In other words, even though an earlier trial showed the new treatment as five times better, a subsequent trial said it was not significantly better at all. We tried to find a rule which worked by increasing the hazard ratio or the significance of the results. We found that we had to increase the hazard ratio to 20 (i.e. the new treatment is 20 times better than the old treatment) before the rule became 100% reliable. Out of the whole Cochrane database there were only four trials that fitted this rule.

So why doesn’t this rule work? The main problem is an effect known as ‘regression to the mean’.  Most of the trials that show dramatic effects are small trials, and we know that a small trial has a better chance of producing a freak result than a large trial through the effects of pure chance. Smaller randomised trials also tend to be of lower quality than larger ones and therefore open to greater degrees of bias. The implications, particularly for surgery, are quite interesting. It’s well known that it’s much harder to perform a large randomised trial in surgery than it is when studying a drug. However, our work adds to the literature showing that small randomised trials are pretty unreliable. Given that they are also very expensive and difficult to do, our results throw into question whether surgeons might be better to do another type of study in situations where they know that they won’t be able to do a large enough randomised trial to avoid the effects we are talking about. There will always be exceptions to this rule, particularly for rare diseases, but our findings could be used to support the idea that in surgery it may be useful sometimes to do a large non-randomised prospective study before committing to the major undertaking of developing a large high quality randomised trial.

The full paper ‘Very large treatment effects in randomised trials as an empirical marker to indicate whether subsequent trials are necessary: meta-epidemiological assessment’ can be read in the BMJ.

For the first time specific antibodies have been found to be associated with the onset of schizophrenia. A study published in The Lancet Psychiatry, reveals that certain kinds of antibodies appear in the blood of a significant percentage of people presenting with a first episode of psychosis. These antibodies, including those against the ‘NMDA receptor’, have previously been shown to cause encephalitis, a life threatening inflammation of the brain. This study now shows for the first time, that these same antibodies are also found in people with early presentations of schizophrenia.

Professor Belinda Lennox from the Department of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, who led the study, says: ‘We have shown that 8.8% of people with a first episode of psychosis have an antibody in their blood that may be responsible for their illness. The only way to detect these antibodies is through doing a blood test, as patients with antibodies do not have different symptoms from other people with psychosis.’

The discovery offers fresh hope in terms of new treatment possibilities for people experiencing psychosis. This is because the rapid identification and removal of the same antibodies associated with encephalitis leads to a dramatic improvement, and often complete a cure from the illness. Professor Lennox and her team have successfully treated a number of patients experiencing psychosis, who have these antibodies, using this pioneering form of immunotherapy.

‘It began with a devastating psychotic episode and subsequent issues with my memory, sleep, temperature and emotional control,’ says Sarah, a patient of Professor Lennox. ‘My mood was in total flux, swinging from hallucinations and insomnia to sleeping all day and getting severely depressed.  It took over a year before the autoimmune side of my illness was picked up on through a fortunate research trial.  Three years following my episode I have finally responded after two infusions of immune drugs. I am regaining nearly all of my previous function. It has been like a miracle cure. It is terrifying to imagine that without the correct treatment my symptoms might never have improved. Psychosis, caused by NMDA antibodies, could have dominated and even claimed my life.’

Professor Lennox adds: ‘The next important step for this study is to work out whether removing the antibodies will treat psychosis in the same established way as is now used for encephalitis. To do this the research team are starting a randomised controlled trial of immune treatment in people with psychosis and antibodies, starting in 2017.’

This study, funded by the Medical Research Council, recruited 228 people with psychosis from Early Intervention in Psychosis services from across England, including Oxford Health NHS Foundation Trust. People were tested within the first six weeks of treatment. The study also tested a comparison group of healthy controls. They found NMDAR antibodies as well as other antibodies, in patients with psychosis. They did not find any NMDAR antibodies in healthy control subjects. When the patients with antibodies were compared with those patients without antibodies there were no differences in their symptoms or illness course.

Antibodies are produced by the immune system to fight infection and protect the body. Sometimes, however, the antibodies cause more problems than they solve – in so-called auto-immune disorders, such as diabetes, multiple sclerosis and rheumatoid arthritis. Psychosis – which is a term for the symptoms seen in schizophrenia – is where a person may experience hallucinations, delusions and confused and disturbed thoughts.

The story of first-hand experience of NMDAR encephalitis was eloquently described by Susannah Cahalan, the New York Post journalist in her book ‘Brain on Fire’, which has since been made into a feature film released this year.

The full paper ‘Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first episode psychosis’ can be read in The Lancet Psychiatry.

In a guest post for Science Blog, Dr Chris Newman, Dr Mike Noonan and Dr Christina Buesching from Oxford's Wildlife Conservation Research Unit (WildCRU) (directed by Professor David Macdonald) write about their latest research into the ecology of climate change – that is, how changing weather conditions affect the abundance and distribution of animal and plant species.

How many people cycle to work in Oxford? Census the number of people cycling in on a sunny summer day and you will surely get a higher estimate than if you count cyclists on a rainy winter day.

This type of sampling bias is extremely pertinent to climate change ecology, because population estimates are based on the number of individuals that are observed, trapped, photographed or otherwise sampled. Nevertheless, studies rarely account for imperfect detection and have tended to assume that population trends are purely a reflection of actual climatic effects, disregarding how weather alters animals' behavioural responses.

In a recent paper published in the journal Global Change Biology, we tested the extent to which prevailing weather might skew the numbers of badgers trapped in a well-studied population at Wytham Woods – Oxford University’s research woodland.

Following 1,179 individual badgers through 3,288 capture-recapture events over 19 years, we found that temperature and rainfall had a substantial effect on badger 'trappability'. Crucially, weather conditions did not act in isolation, but interacted with how fat badgers were. This curious discovery exposes an important and often underappreciated factor: motivation.

Returning to our cycling analogy, if your job and livelihood depend on your cycling to work, the chances are you will readily – though perhaps begrudgingly – cycle in rain, hail, or snow. If you can easily work from home, however, or take a vacation day, the weather will have little effect on your behaviour.

Badgers, as it turns out, are no different. Their behaviour is heavily influenced by motivation, and thus our ability to census them is heavily influenced by changes in their behaviour. Badgers, of course, live in underground burrows called setts and can only be 'caught' – observed or camera-trapped – when venturing above ground.

While all badgers were less inclined to surface in wet, miserable conditions, fatter badgers had the luxury to be more choosy about when to emerge, living off stored fat reserves until better conditions presented themselves. Thin and more desperate badgers on the other hand, got caught even when poor weather prevailed.

From an ecological perspective, if not accounted for, this skewed sub-sample would also give the impression that badgers are thinner with prevailing wet weather. In reality, quite the opposite is true: because badgers eat earthworms that surface in cool, wet conditions, they tend to be fatter following periods of wetness. This leads to a reinforcing loop, where fatter badgers are harder to catch. Consequently, when the population was generally in good condition, fewer badgers were caught, and vice versa.

More problematic still is that the difference of around 10% in trappability we recorded between best and worst weather scenarios is amplified further by capture-mark-recapture statistical models used to estimate actual population size from patchy individual trap histories. If worst-case-scenario weather is perpetuated over several consecutive seasonal trap-ups, it could cause up to a 55% population underestimate, whereas sustained best-case weather could lead to a 39% overestimate.

Now, there are direct practical implications to these findings. Badgers are culled in the UK in an attempt to alleviate the spread of bovine tuberculosis (bTB) in cattle. But failures by DEFRA to meet cull targets, and thus to achieve a worthwhile level of decrease in badger populations, have attracted criticism. In 2014, only 341 of the targeted 316-435 badgers were culled in Somerset, and only 174 of the targeted 615-1091 in Gloucestershire.

Extrapolating from our findings, it was immediately apparent that relatively cold, wet conditions during that autumn had done DEFRA's cull no favours. If warmer and drier conditions had occurred, the Somerset cull would likely have got close to its upper quota target – but in Gloucestershire, although trapping success would have been better, it would still have been fallen short of minimum quota targets.

Two crucial points emerge from our work. First, in terms of climate change logic, because there has been a steady trend for global warming over the last century, everything else developing over this period correlates with global warming – that is, correlation does not imply causality. This has been neatly satirised by Bobby Henderson's internet spoof, which shows a statistically significant relationship between increasing temperatures and the shrinking numbers of pirates since the 1800s. Studies on climate change must therefore focus on the precise mechanisms involved, avoiding spurious correlations.

Second, because an animal will initially attempt to respond to inclement weather by modifying its behaviour, population-level effects on reproduction and survival will only become apparent when conditions become too extreme for individuals to adapt to – where only long-term studies can elucidate genuine population trends from variation due to unanticipated correlations.

In short, the risks posed by climate change to species and ecosystems, as well as to human enterprises, are too serious for us to get things wrong. As the bTB example shows, management interventions or conservation strategies, implemented under unsuitable weather conditions, will fall short of targets. If the predictions made by scientists are based on faulty data, policies based on these data are destined to fail, adding to the malaise of misguided opinion surrounding global warming.