Visiting the Natural History Museum Darwin Centre

Today my friends and I went to see the Darwin Centre at the Natural History Museum, and it was AMAZING!

Cocoon 1The aim of this shiny new wing is to show visitors “the hidden world of museum science”.

The Natural History Museum is rightly most famous for it’s natural history collection, which comprises more than 70 million specimens amassed over the past 400 years. However, the museum is also an active research centre that covers biodiversity, disease, climate change and environmental science.

The striking Cocoon building at the Darwin Centre combines these two arms of the museum’s mission, housing over 200 working scientific experts and also a significant proportion of the museum’s specimens.

The specimens are in storerooms on the lower five floors in a controlled environment behind 4cm glass windows.  And the scientists?  They’re also on display behind glass windows, allowing guests to get a glimpse of science in action; for example, the preparation of specimens for cataloging or the extraction of DNA for sequencing.

GScientists as lab ratsiven my geeky tendencies, I particularly enjoyed the Decoding DNA area. This spot explained how and why scientists unravel DNA, and included a funky animation of PCR. One of the things I really liked about the whole Darwin Centre was that it explained the practicalities of what scientists do, and the clear explanation the rather complicated process of DNA sequencing was a great example.

Malaria gameThe Decoding DNA area also had a cool game about sequencing the DNA of various disease carrying mosquitoes.  You first had to catch enough mosquitoes to fill your quota of PCR tubes, then run them on your virtual electrophoresis gel to get a look at the variation among different types of mosquitoes.  Once you knew what the different types were, you were given a list of their characteristics and asked how you think they should be controlled.

We suggested that our drug resistant Anopheles species of mosquito should be controlled with nets rather than drugs, and totally won the game.  Curing malaria isn’t bad for a morning’s work!

The Cocoon has more than 40 high-tech installations and hands-on interactive activities like this.  Some of my other favourites included a video about peer review and publishing research (predictable? me?!) and a collection of videos of scientists on field expeditions.  More great info on the day to day lives of Britain’s scientists.

Nature plus

Dotted around the exhibition are various barcode scanners for the museum’s NaturePlus scheme.  Each visitor is given a card with a unique barcode that they can scan at exhibits they find particularly interesting and save content to view later online.

I imagine this service is really helpful for school children who are working on a project about taxonomy, for example.  The kids can find out the basics about classification of organisms on their trip to the museum, then do further research about Linnaeus and co when they get home.

Overall I think the Darwin Centre is a great resource for teaching the general public, especially kids, about what it means to be a scientist.  Certainly when I was at school we learnt about DNA, photosynthesis, and so on, but were taught little about how this information was acquired bar the stories of big names like Darwin and Mendel.  The great “how to do biology” exhibition in the Darwin Centre would have no doubt filled the gaps in my schoolgirl knowledge and given me a clear idea of what further studies in science might eventually lead to.

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Switching from paper to patient – taking part in a clinical trial

tracera_logoI make a living reading clinical research papers and am familiar with the big picture of clinical trials – papers published, guidelines amended and practice improved.  Grassroots clinical research – the work of doctors, nurses and patients undertaking a trial – has always seemed like a million miles away to me.

However, I’m hoping to get a new perspective on the nuts and bolts of how clinical research is conducted as my Dad is currently taking part in a huge rheumatoid arthritis trial – the TRACE RA trial.  This study is investigating whether heart drugs – statins – reduce the risk of heart attack and stroke in people with rheumatoid arthritis.

People with rheumatoid arthritis are at higher risk of cardiovascular disease than the general population and are thus are more likely to have a fatal heart attack or stroke.  This increased risk is thought to be due to a higher incidence of atherosclerosis in patients with rheumatoid arthritis – the inflammation that attacks the joints in such people is though to also affect the lining of their blood vessels.

Statins reduce “cardiovascular disease events” and mortality in high risk populations, largely through lowering cholesterol but also possibly through reducing inflammation.  We don’t know whether statins are beneficial in rheumatoid arthritis though, as people with this highly inflammatory condition are usually excluded from statin trials.

The TRACE RA trial is a prospective, 5-year, multicentre, randomised, double blind, placebo-controlled study that will assess the hypothesis that a statin is more effective than a placebo in the primary prevention of cardiovascular events in patients with rheumatoid arthritis.

Up to 4,000 people over the age of 50 who have had rheumatoid arthritis for at least 10 years are being randomised to receive either the statin atorvastatin or placebo daily. The patients in the trial will be followed up for up to 7 years to see if those on the statin are less likely to have a cardiovascular event than those on the placebo.

My Dad joined the trial quite recently and is currently going through his initial follow-up visits, which take place at 3, 6 and 12 months. At each visit he gives a blood sample and also fills in a questionnaire, which he showed me last time I visited. Dad was a bit concerned about the questionnaire, as he was being asked quite dramatic things like whether he was able to dress himself or cut up his own food. Thankfully his arthritis is well controlled and he doesn’t have any mobility problems, so he can answer “no” to most the questions; I’m guessing other trial participants aren’t so lucky.

The questionnaire he has to fill in is a validated tool for assessing functional disability called the Health Assessment Questionnaire (HAQ).  I’ve come across the questionnaire when reading rheumatology papers – it’s used in patients with a wide variety of rheumatic diseases including rheumatoid arthritis, osteoarthritis, lupus, and ankylosing spondylitis – so I was intrigued to get a proper look at it.

Given how much I go on about clinical research, Dad was keen to be involved in a trial himself and hopefully contribute a small part to improving treatment for rheumatoid arthritis.  There’s also a history of heart disease in my family, so (potentially) receiving a statin when he otherwise wouldn’t be on the list to do so could prove doubly beneficial for Dad.

I’m looking forward to following my Dad’s progress in the trial and reading the first published paper.  The design of the trial seems pretty solid so any positive findings could have considerable implications for how patients with rheumatoid arthritis are treated.  And my Dad – subject number whatever out of n=4000 or so – is playing his own little part.

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Wellcome Image Awards: shedding light on the microscopic world

This week medical charity the Wellcome Trust presented their annual image awards, which highlight the best new pictures acquired in the past 18 months by their free picture library.

The prizes are awarded to “the creators of the most informative, striking and technically excellent images” on the basis of “the ability of the picture to communicate the wonder and fascination of science.”

Dr Alice M Roberts, who presented the awards, emphasised not only the utility of images in science, but also their value as beautiful work of art.  “Imaging and imagery can help scientists in many ways: to understand structures that are too small to be seen by the naked eye, or perhaps to elucidate the relationship between structure and function,” she said. “But as well as deepening understanding, the art of science can also be – in its own right – beautiful and awe-inspiring.”

My favourite images are those created using microscope techniques like electron microscopy and multiphoton microscopy, which provide an extraordinary insight into the detail of human anatomy.

This first picture is of villi in the small intestine – finger-like structures that absorb nutrients from the food passing through the gut.  Paul Appleton, who produced this image using fluorescent imaging techniques, hopes that it might help researchers identify cancerous change in colon tissue, pointing out that “Scientists have to characterise normal tissue before they can look for changes in abnormal tissue.”

SI villi

Another of my favourites is this vivid picture of capillaries from a structure in the eye known as the ciliary body, which sits either side of the lens.  Capillaries measure 5-10 micrometres in diameter and are only one cell thick, so getting such a clear and informative image of these tiny vessels is quite an achievement.  The bright red colour is the result of a dye – likely to be carmine dye – that was injected into the artery that supplied the capillaries.


Number three is this picture of compact bone – the dense stuff that surrounds the bone marrow.  The structures that look like rings in a tree stump are called osteons, in which lamellae of bone tissue form around canals that house the blood and nerve vessels supplying the bone.  The black specks show osteocytes, the living cells that produce bone tissue.  The cells are lost during processing, however, leaving the holes within the bone that they once occupied.  Unlike the previous images, no false colour was added to this picture.  Your intestines aren’t blue and red like the image of villi above, but your bone definitely looks like this.

compact bone

Last is this image of in vitro fertilization.  The “blazing sun” object is the egg, the “rays” produced by cumulus cells that protect the egg.  This image shows the moment of conception, with a sperm wiggling its way in on one side.


These images and more are available to view on the Wellcome Trust Image Awards website.  They’re also on display until Spring 2010 in a free exhibition at the Wellcome Collection.

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Sacre bleu! French diet doesn’t meet nutrient recommendations

Typical French dishFrench food is famous around the world.  From the haute cuisine espoused by cordon bleu and the Michelin Guide to weird and wonderful dishes like frogs legs, the French are passionate about cooking and what they eat.

However, a study published recently in the Journal of Nutrition has found that the diet consumed by the majority of French adults doesn’t meet nutrition recommendations.  Only 22% of adults could meet dietary requirements by fine tuning what they already ate, whereas the remaining 78% of French adults would need to expand their diet.

The authors of this study used modelling techniques to create diet plans based on an individual’s “habitual food repertoire” – i.e. the kinds of foods they regularly consumed.  The idea of this approach was to calculate a diet plan that met nutritional recommendations without deviating much from the foods the individual already liked to eat.

More than a thousand French adults who were participating in the French national food consumption study provided seven day food diaries. The authors then tried to design for each individual a diet plan that met 30 different food recommendations by using the foods in their weekly food repertoire.  The designed diets varied according to the individual’s gender, age and observed nutrient intake levels.

The authors found that they could only put together diets that met all 30 recommendations for 22% of adults – i.e. only a fifth of the sample had diets that could be tweaked to be nutritionally sound on the basis of how foods were combined or how big portion sizes were.  These individuals consumed more energy and more fruit and vegetables than those whose food repertoire couldn’t be juggled to meet requirements.

On the other hand, it was mathematically impossible to design a nutritionally adequate diet for the remaining 78% without extending the range of foods they ate.  The main problem among participants with unsatisfactory diets was that their favourite foods didn’t contain enough vitamin D, although their diet plans also couldn’t be manipulated to within maximum sodium levels or minimum magnesium recommendations.

Unsurprisingly, feasible diets could be put together for every participant when the food options were not limited to the individual’s food repertoire.

This study suggests not only that the diets of most French adults aren’t anywhere near meeting nutrition requirements, but also that considerable changes will need to be made to the foods eaten in order to meet a healthy diet.  Maybe French food isn’t all it’s cracked up to be after all…

Maillot M et al. (2009) To Meet Nutrient Recommendations, Most French Adults Need to Expand Their Habitual Food Repertoire. Journal of Nutrition 139 (9): 1721-1727. DOI: 10.3945/jn.109.107318

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Do clinical trial registries reduce selective reporting of medical research?

Stack of papersNot really, say two studies recently published articles in JAMA and PLoS Medicine that scrutinized studies in various clinical trial registries.

The idea of trial registries is that researchers provide all the details of their study – such as the number of patients they need to recruit and the primary outcome (e.g. death or heart attack) – before they start the study. Then once the study has been completed and published, other people can refer to the record in the registry to see whether the pre-specified protocol has been followed and if the researchers have really done what they said they were going to do and how they said they were going to do it.

The JAMA study compared published articles with their entries in clinical trial databases and found that less than half of the 323 published articles in their sample were adequately registered and nearly a third weren’t registered at all.  Shockingly, 31% of adequately registered trials published different outcomes from the outcomes registered on the clinical trial databases – that is, the authors “changed their mind” about what they were researching at some point in the process.

The authors of the PLoS paper did their research the other way around and looked at whether trials in, the registry set up by the US National Institutes of Health and the Food and Drug Administration, went on to be published.  Less than half of the 677 trials they studied were eventually published.  Trials sponsored by industry and, interestingly, trials funded by the government were less likely to be published than those funded by nonindustry or nongovernmental sources.

Why is this important? Imagine a group of researchers are looking into whether an new drug reduces the incidence of heart attack (the primary outcome). They spend thousands of pounds recruiting patients and studying them for years and years, then find out that their drug doesn’t prevent heart attack at all but is very helpful in patients with migraine. The researchers could then decide to change the primary outcome of their study from “incidence of heart attack” to “incidence of migraine”, even though the trial had been intricately designed to look at the former not the latter. Their statistics and results will be all out of whack and frankly unreliable, but they could still go ahead and market their blockbuster drug. Researchers could get away with this if they don’t put their trial details in a registry before they started.

Imagine that the wonder cardiovascular drug our shady researchers are investigating has no effect whatsoever on heart attack, so the researchers just decide not to publish their results. Other researchers looking at very similar drugs could plod on for ages with their own experiments to no avail because they had no idea that someone else had already shown the drug was useless. A more disconcerting possibility is that a drugs company could find out their key money spinner has a nasty side effect but decide to bury the research showing this and never publish it.  This is known as publication bias. Researchers, funding bodies and editors are all more interested in publishing studies that find something interesting rather than ones that show nothing at all – where’s the headline in “candidate drug doesn’t do much”? When it comes to drugs that are already on the market though, knowing the situations in which the drug doesn’t work is just as important as knowing when it does work.

And from a patient perspective? Imagine your doctor has been prescribing you a drug that should help your stomach ulcers. What he doesn’t know is that an unpublished trial somewhere says the drug will also dangerously thin your blood. If the doctor has no idea this trial ever existed – it wasn’t registered when the trial kicked off and was never published – or the negative results were masked by the paper reporting a different primary outcome to that in a registry, he or she will continue prescribing you a drug with risky side effects.  The example of arthritis drug Vioxx springs to mind…

These are all quite dramatic examples but illustrate why we need to know about trials at their inception rather than once they’re published and, therefore, why full use of clinical trial registries is important.

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Aspirin in colorectal cancer – a new trick for an old dog

AspirinA new study published in JAMA this week has shown that in patients with colorectal cancer, taking an aspirin a day after diagnosis reduces the risk dying from the cancer or from any cause by at least 20%.  Taking aspirin before diagnosis, however, did not have any effect of prognosis.

It has been known for a few years that regular aspirin use can reduce the risk of developing colorectal cancer.  This drug isn’t a good idea as a preventive strategy though as it is associated with gastrointestinal irritation and bleeding – pretty serious side effects.  What this new study shows is that when it comes to colorectal cancer, aspirin might be just as effective and more practical as a treatment for people who already have the disease.

In this study, the authors first followed a whopping 170,000 health professionals for 20 years.  The 1279 men and women who developed colorectal cancer then completed a survey on aspirin use every two years for a further 7-10 years.

The majority of people who used aspirin reported taking the drug as an analgesic, mostly for headache or arthritis and other musculoskeletal pain.  A notable proportion, men in particular, took aspirin for cardiovascular disease prevention, which this handy little drug has also proved effective at.

Compared with participants who did not use aspirin, people who regularly used aspirin either after diagnosis only or both before and after diagnosis were 29% less likely to die from colorectal cancer and 21% less likely to die from any cause.  On the other hand, aspirin had no effect on mortality risks in people who took aspirin before cancer diagnosis only or both before and after diagnosis.

When the analysis was restricted to people who started taking aspirin after diagnosis only,  the risks of cancer-specific mortality and overall mortality were 47% and 32% lower than in those who didn’t take aspirin at all.  Conversely, there was no benefit seen specifically in the group that took aspirin before diagnosis and continued once they knew they had colorectal cancer.

The effect of aspirin in colorectal cancer was particularly strong in patients whose primary tumors overexpressed the enzyme cyclooxygenase 2 (COX-2), which crops up in about 80% of colorectal cancers, suggesting that aspirin might be an effective treatment in the majority of people with this type of cancer.  The amount of aspirin consumed also altered the effect – the mortality risk was slightly lower in people who took 6 or more tablets a week than in those who took 0.5 to five a week.

In an accompanying editorial, Alfred Neugut at Columbia University states that “aspirin may become standard adjuvant therapy in the management of colorectal cancer.” This treatment has the added advantage of being highly specific to are therefore only useful in patients with tumors that overexpress COX-2, so that “this potential future treatment comes with its own ready-made predictive biomarker.”

Chan AT, Ogino S, Fuchs CS (2009) Aspirin Use and Survival After Diagnosis of Colorectal Cancer JAMA 302 (6): 649-658 LINK

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Does IQ affect cardiovascular disease risk?

IQErr, well, maybe.  IQ does seem to account for some of the well-documented relationship between socioeconomic status and cardiovascular risk, according to new research in European Heart Journal.  Simply put, being more intelligent could be one reason why people from a high socioeconomic background are less likely to die from cardiovascular disease than those who are more disadvantaged.

The authors of this study wanted to unravel how low socioeconomic status leads to cardiovascular disease and poor health.  Factors like access to resources (e.g. education and income) and environmental exposures (e.g. housing conditions) have a role, but taking account of these factors in calculations – effectively eliminating their influence – doesn’t level the playing field, meaning that there must be some other elements at play.

Previous studies have shown that IQ is inversely correlated with total mortality and cardiovascular mortality – that is, people with a high IQ are at least risk of death from any cause and death from heart disease.

Batty et al. looked at data from 4,289 male former US soldiers to establish the extent to which IQ ‘explains’ socioeconomic disparities in health.  All participants took a general aptitude test when they joined the army between 1965 and 1971.  Results from this test, as well as data on their income at 20 years of age, were combined with IQ, health and financial data gleaned from a telephone survey when the participants were on average 38 years old.

As expected, men who had a high IQ – both at 20 years old and at middle age – tended to have more favourable social circumstances, such as higher family income, than those with a lower IQ.

In a second analysis, socioeconomic status was inversely associated with total mortality, cardiovascular mortality and death from any cause.  For example, men with a low current income or little education were more than six times more likely and three times more likely, respectively, to die from cardiovascular disease.

When the calculations were adjusted to take into account IQ scores at 20 years old, the huge differences in cardiovascular mortality between those who were well off and those who were less fortunate shrunk by a third; the disparity was reduced by more than half when IQ score at middle age was added instead.

Adjusting for other risk factors for cardiovascular disease – such as blood pressure and cholesterol level – had less of an effect on the mortality differences between the most fortunate and the least fortunate, suggesting that IQ has more of an effect on risk of cardiovascular disease according to socioeconomic status than do traditional risk factors.

The implication of this study is that efforts directed at reducing socioeconomic disadvantage to improve health should also include educational opportunities as well as improving housing and so on.
Batty G et al. (2009) Does IQ explain socio-economic differentials in total and cardiovascular disease mortality? Comparison with the explanatory power of traditional cardiovascular disease risk factors in the Vietnam Experience Study. European Heart Journal 30 (15): 1903-1909. DOI: 10.1093/eurheartj/ehp254

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Multiple choice medical school exams favour male students

ExamUrgh, exams. The epic ‘true-false-no idea’ multiple choicers of my undergraduate days are not a distant enough memory for me. The whole ‘get it right, get 1 point’, ‘get it wrong, lose 1 point’ approach always seemed horrendously unfair, regardless of the statistical basis for the strategy (i.e. examiners don’t want to reward people that guess true or false on every question, as in theory they’ll get the right answer 50% of the time).

According to researchers at University of Nottingham, my personal MCQ fear is well founded. Shona Kelly and Reg Dennick have found that male medical students are much more likely to do well on an exam with some ‘true-false-abstain’ questions than are female students.

The authors of this study looked at seven years worth of results from medical school course assessments – which included course work, essays, in-class assessments, lab studies, Objective Structured Clinical Examinations (OSCEs), short answer tests, single phrase tests, spotter quizzes, single word answer exams, true-false-abstain questions, and Vivas.

Among the 359 course assessments, there was a statistically significant difference in the marks between the genders in a third of the courses in any given year. Univariate analyses indicated that women did better in assessments that included some in-class assessment and some short answer questions, but struggled with exams that included true-false-abstain questions. Men did better on assessments with some true-false-abstain questions and were at a disadvantage in those that included some short answer questions.

The female advantage seen with in-class assessment disappeared in multivariate analyses that took into account the subject area/content of the assessment and calendar year, however, and the advantage that females seemed to have in exams with short answer questions was very small (odds ratio 1.03).

On the other hand, the association between true-false-abstain and male advantage wasn’t affected in multivariate analyses. In fact, males were 16.7 times more likely to score higher than females if at least some true-false-abstain questions were in the assessment. This difference could be down to the fact that women were more likely to pick the ‘abstain’ option in this format exam.

So there’s the answer. My difficulty with university exams clearly had nothing to do with my preparation and was obviously down to the inherent gender bias in the format used for biomedical exams.  Cough.

Kelly S & Dennick R (2009) Evidence of gender bias in True-False-Abstain medical examinations. BMC Medical Education 9(1). DOI: 10.1186/1472-6920-9-32

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Cycling or walking to work reduces risk of obesity and cardiovascular disease… but only in men

Cycling to workOK, so it seems pretty obvious that cycling or walking to work is better for you than taking the car. New research published in Archives of Internal Medicine has clarified the beneficial effects in terms of fitness and cardiovascular health of walking or cycling to work – but they’re largely only seen in men.

This study assessed 2,364 adults from four US states, and found that less than a fifth (16.7%) used active means to get to work. Men who walked or cycled to work were fitter (able to run for longer on a treadmill) and were less likely to be obese (had a lower body mass index) than those who commuted by car, bus, train or subway.  Female active commuters were fitter than their more sedentary counterparts, but no less likely to be obese.

In addition, men who walked or cycled to work were at lower risk of cardiovascular disease, as they had lower levels of a range of cardiovascular disease biomarkers (i.e. blood levels of triglycerides and fasting insulin, and diastolic blood pressure).  This inverse correlation was not seen in women though.

So why the difference between men and women?  Well, women were less likely to be active commuters (15.6% of women versus 18.0% of men), and those who were active commuters were more likely to walk than cycle (82.8% in women versus 64.1% in men).  Although the median distance to work for active commuters was 5 miles for both men and women, men would cycle or walk up to 13.5 miles whereas the maximum commute in women was 10 miles.  It seems that women need to commute a bit further and at a higher intensity of exercise in order to see weight and cardiovascular benefits of active commuting.

The authors of this study conclude that nonleisure forms of exercise such as active commuting can help people increase their levels of physical activity and have beneficial effects on health.
Penny Gordon-Larsen, Janne Boone-Heinonen, Steve Sidney, Barbara Sternfeld, David R Jacobs Jr, Cora E Lewis (2009) Active Commuting and Cardiovascular Disease Risk: The CARDIA Study. Arch Intern Med 169(13): 1216-1223. PMID: 19597071

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Junior doctors pressed into taking HIV tests

Blood testJunior doctors are undergoing HIV tests as part of pre-employment occupational health checks without being made aware that such testing is not mandatory, according to research published in the Journal of Medical Ethics.  Many junior doctors interviewed by Lee Salkeld and colleagues held the misperception that HIV testing was compulsory and felt unable to decline the test.  In addition, interviewees felt that they had not been provided with enough information about the test or about the impact of a positive result.

According to guidance published by the Department of Health in 2007, all new healthcare workers need to undergo tests for tuberculosis and hepatitis B, and should be immunised as necessary. Only those who will perform exposure-prone procedures – i.e. people who will undertake invasive procedures where there is a risk that the patient’s open tissues could be exposed to the blood of the worker – are required to have an HIV test.

Several of the 24 junior doctors (foundation years 1 and 2) and doctors in specialty training (years 1, 2 and 3) interviewed by Salkeld et al., however, commented that the requirement of an HIV test was simply presented as just another part of a long list of tests that were necessary.

This lack of pre-test discussion meant that most of the doctors were unclear about the implications of a positive HIV test. One even asked: “I wonder if they’d have sacked me if it was positive. No one really explained what would happen if it were positive either—would my bosses have been told about it?”

The DoH guidance suggests that healthcare workers could benefit from these regulations “both personally and professionally”.  Most of the junior doctors interviewed by Salkeld et al. thought that HIV testing was for the benefit of patients, though; few mentioned the benefit to themselves of knowing their HIV status and being able to access treatment should they be HIV positive. 

There have been only two cases of HIV transmission from doctors to patients worldwide – one involving an orthopaedic surgeon and the other an obstetrician, neither of whom were practising in the UK. The risk of HIV transmission from healthcare worker to patient is eximated to be between 1 in 42,000 and 1 in 420,000, although the risk of patient-to-doctor transmission is 1 in 300.

Given these figures, the authors ask “is this somewhat utilitarian Department of Health policy justifiable?”
Salkeld L et al. (2009) HIV testing of junior doctors: exploring their experiences, perspectives and accounts Journal of Medical Ethics 35 (7): 402-406. DOI: 10.1136/jme.2008.027052

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