Empirical entropic contributions in computational docking: Evaluation in APS reductase complexes

The results from reiterated docking experiments may be used to evaluate an empirical vibrational entropy of binding in ligand–protein complexes. We have tested several methods for evaluating the vibrational contribution to binding of 22 nucleotide analogues to the enzyme APS reductase. These include two cluster size methods that measure the probability of finding a particular conformation, a method that estimates the extent of the local energetic well by looking at the scatter of conformations within clustered results, and an RMSD-based method that uses the overall scatter and clustering of all conformations. We have also directly characterized the local energy landscape by randomly sampling around docked conformations. The simple cluster size method shows the best performance, improving the identification of correct conformations in multiple docking experiments. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60220/1/20936_ftp.pd

Substance use and its predictors among undergraduate medical students of Addis Ababa University in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Substance use remains high among Ethiopian youth and young adolescents particularly in high schools and colleges. The use of alcohol, <it>khat </it>and tobacco by college and university students can be harmful; leading to decreased academic performance, increased risk of contracting HIV and other sexually transmitted diseases. However, the magnitude of substance use and the factors associated with it has not been investigated among medical students in the country. This study was conducted to determine the prevalence of substance use and identify factors that influenced the behavior among undergraduate medical students of Addis Ababa University in Ethiopia.</p> <p>Methods</p> <p>A cross-sectional study using a pre-tested structured self-administered quantitative questionnaire was conducted in June 2009 among 622 medical students (Year I to Internship program) at the School of Medicine. The data were entered into Epi Info version 6.04d and analyzed using SPSS version 15 software program. Descriptive statistics were used for data summarization and presentation. Differences in proportions were compared for significance using Chi Square test, with significance level set at p < 0.05. Multivariate logistic regression analyses were used to assess the magnitude of associations between substance use and socio-demographic and behavioral correlates.</p> <p>Results</p> <p>In the last 12 months, alcohol was consumed by 22% (25% males vs. 14% females, p = 0.002) and <it>khat </it>use was reported by 7% (9% males vs. 1.5% females, p < 0.001) of the students. About 9% of the respondents (10.6% males vs. 4.6% females, p = 0.014) reported ever use of cigarette smoking, and 1.8% were found to be current smokers. Using multiple logistic regression models, being male was strongly associated with alcohol use in the last 12 months (adjusted OR = 2.14, 95% CI = 1.22-3.76). Students whose friends currently consume alcohol were more likely to consume alcohol (adjusted OR = 2.47, 95% CI = 1.50-4.08) and whose friends' use tobacco more likely to smoke (adjusted OR = 3.89, 95% CI = 1.83-8.30). <it>Khat </it>use within the past 12 months was strongly and positively associated with alcohol consumption (adjusted OR = 15.11, 95% CI = 4.24-53.91). Similarly, ever use of cigarette was also significantly associated with alcohol consumption (adjusted OR = 8.65, 95% CI = 3.48-21.50).</p> <p>Conclusions</p> <p>Concordant use of alcohol, <it>khat </it>and tobacco is observed and exposure to friends' use of substances is often implicated. Alcohol consumption or <it>khat </it>use has been significantly associated with tobacco use. While the findings of this study suggest that substance use among the medical students was not alarming, but its trend increased among students from Year I to Internship program. The university must be vigilant in monitoring and educating the students about the consequences of substance use.</p

Khat and alcohol use and risky sex behaviour among in-school and out-of-school youth in Ethiopia

BACKGROUND: Khat (an evergreen plant with amphetamine-like properties) and alcohol are widely consumed among the youth of Ethiopia. However, their relationship to risky sexual behaviour is not well described. This study was conducted to describe the magnitude of risky sexual behaviour (unprotected sex and early initiation of sexual activity) and its association with Khat and alcohol consumption in Ethiopian youths. METHODS: A probabilistic national sample of 20,434 in-school and out-of-school youths aged between 15 and 24 years of age was selected and interviewed regarding their sexual behavior and substance use. RESULTS: Over 20% of out-of-school youth had unprotected sex during the 12-month period prior to interview compared to 1.4% of in-school youth. Daily Khat intake was also associated with unprotected sex: adjusted OR (95% CI) = 2.26 (1.92, 2.67). There was a significant and linear association between alcohol intake and unprotected sex, with those using alcohol daily having a three fold increased odds compared to those not using it: adj. OR (95% CI) = 3.05 (2.38, 3.91). Use of substances other than Khat was not associated with unprotected sex, but was associated with initiation of sexual activity: adj. OR (95% CI) = 2.54 (1.84, 3.51). CONCLUSION: A substantial proportion of out-of-school youth engage in risky sex. The use of Khat and alcohol and other substances is significantly and independently associated with risky sexual behaviour among Ethiopian youths

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Safeguards issues in spent fuel consolidation facilities

In the nuclear power industry, the fuel assembly is the basic unit for nuclear material accountancy. The safeguards procedures for the spent fuel assemblies, therefore, are based on an item accountancy approach. When fuel consolidation occurs in at-reactor'' or away-from-reactor'' facilities, the fuel assemblies are disassembled and cease to be the basic unit containing nuclear material. Safeguards can no longer be based on item accountancy of fuel assemblies. The spent fuel pins containing plutonium are accessible, and the possibilities for diversion of spent fuel for clandestine reprocessing to recover the plutonium are increased. Thus, identifying the potential safeguards concerns created by operation of these facilities is necessary. Potential safeguards techniques to address these concerns also must be identified so facility designs may include the equipment and systems required to provide an acceptable level of assurance that the international safeguards objectives can be met when these facilities come on-line. The objectives of this report are (1) to identify the safeguards issues associated with operation of spent fuel consolidation facilities, (2) to provide a preliminary assessment of the assessment of the safeguards vulnerabilities introduced, and (3) to identify potential safeguards approaches that could meet international safeguards requirements. The safeguards aspects of spent fuel consolidation are addressed in several recent reports and papers. 11 refs., 3 figs., 3 tabs