Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials

Prevalence of Self-Medication of Psychoactive Stimulants and Antidepressants among Undergraduate Pharmacy Students in Twelve Pakistani Cities

Purpose: To evaluate the prevalence of self-medication of psychoactive stimulants and antidepressants among pharmacy students of Pakistan.Methods: A cross-sectional survey on self-medication of psychoactive stimulants and antidepressants among pharmacy students was conducted with a structured and validated questionnaire distributed to a total of 2981 final year undergraduate pharmacy students in 12 major Pakistani cities (Karachi, Lahore, Islamabad, Rawalpindi, Sargodha, Dera Ismail Khan, Abbottabad, Bahawalpur, Hyderabad, Faisalabad, Multan and Peshawar) of Pakistan. Out of this, 2516 (718 male and 1798 female) students completed and returned the questionnaire.Results: Prevalence of self-medication of psychoactive stimulants was 1.31 (1.13 – 1.75 for 95% CI) and antidepressants was 8.34 (8.03 – 8.85 for 95% CI). A majority of the students (63 %) identified academic competition as a driving force for indulging in self-medication of psychoactive stimulants while nearly all the students (96 %)admitted using antidepressants to obtain relief from the pressure of studies (p < 0.05).Conclusion: Pakistani pharmacy students, despite being aware of the hazards of psychoactive stimulants, indulge in self-medication. Prevalence of self-medication with antidepressants is very high among the students due to the pressure of studies. Primarily, academic competition is the major driving force for the use of psychoactive stimulants.Keywords: Self-medication, Psychoactive stimulants, Antidepressants, Pharmacy students, Academicpressur

Sphalerons and the Electroweak Phase Transition in Models with Higher Scalar Representations

In this work we investigate the sphaleron solution in a $SU(2)\times U(1)_X$ gauge theory, which also encompasses the Standard Model, with higher scalar representation(s) ($J^{(i)},X^{(i)}$). We show that the field profiles describing the sphaleron in higher scalar multiplet, have similar trends like the doublet case with respect to the radial distance. We compute the sphaleron energy and find that it scales linearly with the vacuum expectation value of the scalar field and its slope depends on the representation. We also investigate the effect of $U(1)$ gauge field and find that it is small for the physical value of the mixing angle, $\theta_{W}$ and resembles the case for the doublet. For higher representations, we show that the criterion for strong first order phase transition, $v_{c}/T_{c}>\eta$, is relaxed with respect to the doublet case, i.e. $\eta<1$.Comment: 20 pages, 5 figures & 1 table, published versio

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

A rare case of arterial avulsion presenting with occult blood loss following total hip arthroplasty: a case report

INTRODUCTION: Iatrogenic arterial damage during total hip replacement is a rare but potentially life- or limb-threatening complication. To the best of our knowledge, this is the first reported case of an avulsion injury to a posterior branch of the profunda femoral artery during primary hip arthroplasty. CASE PRESENTATION: We describe the case of a 55-year-old Caucasian man who underwent a total hip replacement. The patient's hemoglobin levels dropped postoperatively, but there was no obvious bleeding, hemodynamic instability, pulsatile mass, or limb ischemia. The patient's hemoglobin levels continued to drop despite nine units of transfused blood. Three days after surgery, the patient underwent an angiography that showed an avulsion injury to a posterior branch of the profunda femoral artery. The avulsion was ligated and the hematoma was evacuated. CONCLUSION: Vascular damage may present in many ways including obvious bleeding, haemodynamic instability, a pulsatile mass, limb ischemia, and occult blood loss. Any of these signs in isolation or in combination could represent a vascular injury and an urgent angiogram should be considered

Quality control and beam test of GEM detectors for future upgrades of the CMS muon high rate region at the LHC

Gas Electron Multipliers (GEM) are a proven position sensitive gas detector technology which nowadays is becoming more widely used in High Energy Physics. GEMs offer an excellent spatial resolution and a high particle rate capability, with a close to 100% detection efficiency. In view of the high luminosity phase of the CERN Large Hadron Collider, these aforementioned features make GEMs suitable candidates for the future upgrades of the Compact Muon Solenoid (CMS) detector. In particular, the CMS GEM Collaboration proposes to cover the high-eta region of the muon system with large-area triple-GEM detectors, which have the ability to provide robust and redundant tracking and triggering functions. In this contribution, after a general introduction and overview of the project, the construction of full-size trapezoidal triple-GEM prototypes will be described in more detail. The procedures for the quality control of the GEM foils, including gain uniformity measurements with an x-ray source will be presented. In the past few years, several CMS triple-GEM prototype detectors were operated with test beams at the CERN SPS. The results of these test beam campaigns will be summarised

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved