A Variant in LDLR is Associated with Abdominal Aortic Aneurysm

Background—Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalysed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance.

Methods and Results—A genome-wide association study was conducted using 1,830 cases from the UK, New Zealand and Australia with infra-renal aorta diameter =30mm or ruptured AAA and 5,435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1x10-4 were carried through to in silico replication in 1,292 AAA cases and 30,503 controls. One SNP associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1,063 controls from the UK, 507 AAA cases and 199 controls from Denmark and 885 AAA cases and 1,000 controls from New Zealand). Low density lipoprotein receptor (LDLR) rs6511720 A, was significantly associated overall and in three of five individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio 0.76; 95% confidence interval 0.70 to 0.83; P=2.08x10-10).

Conclusions—LDLR rs6511720 is associated with abdominal aortic aneurysm. This finding is consistent with established effects of this variant on coronary artery disease. Shared aetiological pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality.

Methods: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case–control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users.

Results: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92).

Conclusions: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Keywords: Colorectal cancer; Breast cancer; Prostate cancer; Mortality; Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

An audit of drug shortages in a community pharmacy practice

Background: There are no firm data on drug shortages in Irish community pharmacy. This prospective observational study aimed to characterise the drug shortage problem in an Irish community pharmacy.
Aims: The primary aim was to determine numbers and durations of drug shortages. Secondary aims included comparing these shortages with Irish Pharmacy Union (IPU) drug shortage lists and determining the frequency with which notifications were received prior to shortages. Further secondary aims were to examine relationships between causes of drug shortages and drug costs and between causes of drug shortages and shortage durations.
Methods: The study took place in a community pharmacy in a Limerick City suburb between October 2012 and February 2013. Data were collected daily regarding drugs that were dispensed, but unavailable to purchase. Suppliers/manufacturers provided data on the reasons for shortages.
Results: 65/1,232 dispensed drugs (5.3 %) were in short supply over the study period. Median shortage duration was 13 days (interquartile range 4–32 days) and median cost was €8.10. Numbers of unavailable drugs by month varied from 13 to 38. Monthly IPU drug shortage lists identified between six and eight of these shortages depending on the month. Two notifications were received from suppliers/manufacturers regarding shortages. Parallel exports had the highest mean costs (mean €38.05) and manufacturing problems were associated with the longest durations (mean 57.44 days).
Conclusions: This study highlights the drug shortage problem in an Irish community pharmacy. We propose that enhanced communication between all stakeholders is the most worthwhile solution. Further studies are needed.

Theory of phonon dissipation in the conduction of stressed Au nanowires

Recent experiments on Au break junctions [Phys. Rev. Lett. 88 (2002) 216803] have characterized the nonlinear conductance of stretched short Au nanowires. They reveal in the voltage range 10-20 meV the signatures of dissipation effects, likely due to phonons in the nanowire, reducing the conductance below the quantized value of 2e(2)/h. We present here a theory, based on a model tight-binding Hamiltonian and on non-equilibrium Green's function techniques, which accounts for the main features of the experiment. The theory helps in revealing details of the experiment which need to be addressed with a more realistic, less idealized, theoretical framework. (C) 2004 Elsevier B.V. All rights reserved.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

Asset Liquidity and Stock Liquidity: International Evidence

This study examines the relationship between asset liquidity and stock liquidity across 47 countries. In support of the valuation uncertainty hypothesis, we find that firms with greater asset liquidity on average have higher stock liquidity. More importantly, our study shows that asset liquidity plays amore significant role in resolving valuation uncertainty in countries with poor information environment. For example, we find that the asset–stock liquidity relationship is stronger in countries with poor accounting standards. We further find evidence that after the adoption of IFRS, the improved accounting information environment results in a weaker asset–stock liquidity relation, but only in countries with a strong legal regime. Finally, our study shows that the positive asset–stock liquidity relationship may be attributed to transparency and/or liquidity reasons.

Quantitative correlation of aflatoxin biomarker with dietary intake of aflatoxin in Tanzanian children

The association between aflatoxin intake from maize-based weaning food and aflatoxin albumin adducts (AF-alb) was investigated in 148 Tanzanian children aged between 12 and 22 months, at 2 visits 6 months apart. At the first visit (storage season) there was a significant correlation at the individual level between AF-alb (geometric mean 43.2 pg/mg albumin) and aflatoxin intake (geometric mean 81.7 ng/kg b.w./d) through maize-based weaning food (r = 0.51, p < 0.01). Overall, this correlation was r = 0.43 (p < 0.01). The AF-alb level in weaning-age children in Tanzania closely reflects aflatoxin intake from maize in weaning food. Exposure levels suggest children may be at risk from aflatoxin associated health effects.

'Sorry I meant the patient's left side': impact of distraction on right/left discrimination

Context Medical students can have difficulty in distinguishing left from right. Many infamous medical errors have occurred when a procedure has been performed on the wrong side, such as in the removal of the wrong kidney. Clinicians encounter many distractions during their work. There is limited information on how these affect performance. 
Objectives Using a neuropsychological paradigm, we aim to elucidate the impacts of different types of distraction on left–right (LR) discrimination ability. 
Methods Medical students were recruited to a study with four arms: (i) control arm (no distraction); (ii) auditory distraction arm (continuous ambient ward noise); (iii) cognitive distraction arm (interruptions with clinical cognitive tasks), and (iv) auditory and cognitive distraction arm. Participants’ LR discrimination ability was measured using the validated Bergen Left–Right Discrimination Test (BLRDT). Multivariate analysis of variance was used to analyse the impacts of the different forms of distraction on participants’ performance on the BLRDT. Additional analyses looked at effects of demographics on performance and correlated participants’ self-perceived LR discrimination ability and their actual performance. 
Results A total of 234 students were recruited. Cognitive distraction had a greater negative impact on BLRDT performance than auditory distraction. Combined auditory and cognitive distraction had a negative impact on performance, but only in the most difficult LR task was this negative impact found to be significantly greater than that of cognitive distraction alone. There was a significant medium-sized correlation between perceived LR discrimination ability and actual overall BLRDT performance. 
Conclusions
Distraction has a significant impact on performance and multifaceted approaches are required to reduce LR errors. Educationally, greater emphasis on the linking of theory and clinical application is required to support patient safety and human factor training in medical school curricula. Distraction has the potential to impair an individual's ability to make accurate LR decisions and students should be trained from undergraduate level to be mindful of this.

Evaluation of Video Presentation to Deliver Surgical Anatomy Teaching

Title Evaluation of Video Presentation to Deliver Surgical Anatomy Teaching

Authors Walsh I.K., Boohan M., Dorman A.

Objectives To evaluate the efficacy of newly introduced video presentation to deliver Surgical Anatomy teaching to undergraduate medical students.

Design and Setting Qualitative and quantitative study using questionnaires and focus groups, employing students undertaking the perioperative medicine module of the phase 4 undergraduate medical curriculum at Queen’s University Belfast.

Outcome Measures To determine:
(1) if video presentation is effective in delivering surgical anatomy teaching,
(2) student’s learning preferences regarding this teaching method.
Results The questionnaire response rate was 89% (216 of 244 students; female: male ratio 1.25) and 42 students participated in 6 focus groups. Mean questionnaire responses indicated a favourable opinion on quality assurance items, with a mixed response to video presentation as a learning method. 71% of students preferred to receive a lecture in person, rather than via video presentation. There were no statistically significant differences between genders regarding learning preferences in general and regarding video versus live presentation in particular. Exploratory factor analysis demonstrated that favourable responses to video presentation were strongly associated with perceived audiovisual quality and learning preferences (Cronbach’s alpha coefficient 0.77), with 72% of students considering video presentation worthwhile. Positive perception of overall quality was strongly associated with learning preferences as well as more generic quality assurance issues (80% students; alpha coefficient 0.83).
The results were supported by triangulation of the above quantitative data with qualitative data generated by the focus groups. Students further articulated the view that video presentation may be more appropriate and effective in a mixed method setting.

Reference Basu Roy R, McMahon GT. Video-based cases disrupt deep critical thinking in problem-based learning. Med Educ 2012 Apr;46(4):426-435.

Should scientific realists be platonists?

Enhanced Indispensability Arguments (EIA) claim that Scientific Realists are committed to the existence of mathematical entities due to their reliance on Inference to the Best Explana- tion (IBE). Our central question concerns this purported parity of reasoning: do people who defend the EIA make an appropriate use of the resources of Scientific Realism (in particular, IBE) to achieve platonism? (§2) We argue that just because a variety of different inferential strategies can be employed by Scientific Realists does not mean that ontological conclusions concerning which things we should be Scientific Realists about are arrived at by any inferen- tial route which eschews causes (§3), and nor is there any direct pressure for Scientific Real- ists to change their inferential methods (§4). We suggest that in order to maintain inferential parity with Scientific Realism, proponents of EIA need to give details about how and in what way the presence of mathematical entities directly contribute to explanations (§5).

Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative

Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative however fails to recognise that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures – Alexander Winchell in the United States, and William Robertson Smith in Britain – who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell’s case from the physical anthropology of human origins and in Smith’s from the cultural anthropology of Semitic ritual.

Electrochemical promotion of catalysis controlled by chemical potential difference across a mixed ionic-electronic conducting ceramic membrane - An example of wireless NEMCA

A La_0.6Sr_0.4Co_0.2F_0.8O₃ mixed ionic electronic conducting (MIEC) membrane was used in a dual chamber reactor for the promotion of the catalytic activity of a platinum catalyst for ethylene oxidation. By controlling the oxygen chemical potential difference across the membrane, a driving force for oxygen ions to migrate across the membrane and backspillover onto the catalyst surface is established. The reaction is then promoted by the formation of a double layer of oxide anions on the catalyst surface. Thelectronic conductivity of the membrane material eliminates the need for an external circuit to pump the promoting oxide ion species through the membrane and onto the catalyst surface. This renders this "wireless" system simpler and more amenable for large-scale practical application. Preliminary experiments show that the reaction rate of ethylene oxidation can indeed be promoted by almost one order of magnitude upon exposure to an oxygen atmosphere on the sweep side of the membrane reactor, and thus inducing an oxygen chemical potential difference across the membrane, as compared to the rate under an inert sweep gas. Moreover, the rate does not return to its initial unpromoted value upon cessation of the oxygen flow on the sweep side, but remains permanently promoted. A number of comparisons are drawn between the classical electrochemical promotion that utilises an external circuit and the "wireless" system that utilises chemical potential differences. In addition a 'surface oxygen capture' model is proposed to explain the permanent promotion of the catalyst activity. © 2007 Springer Science+Business Media, LLC.