Community resilience in the face of community violence

This qualitative study was created to learn more about communities that are labeled as dangerous by external sources. This research explores how organizations and community groups in cities nationally ranked as violent cultivate resilience within the community. People who work in these cities completed an online survey answering qualitative and demographic questions. The study found that respondents portrayed their communities of work and resilience within those communities in complex ways offering increased insight into resilience at the mezzo level. Themes of community cohesion, organizational collaboration, and community violence were present in several responses. The research concludes that while violence is part of many participants\u27 experience, resilience, strength, unity, passion, and organization are also present and working to counteract the negative impacts of violence. The study concludes that further research would be helpful in better understanding and expanding communities\u27 abilities to utilize their strengths

Missing Heritability in the Tails of Quantitative Traits? A Simulation Study on the Impact of Slightly Altered True Genetic Models

Objective: Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in a bimodal mixture situation on the power to detect associations. Methods: We performed simulations of quantitative phenotypes analysed by standard linear regression and dichotomized case-control data sets from the extremes of the quantitative trait analysed by standard logistic regression. Results: Using linear regression, markers with an effect in the extremes of the traits were almost undetectable, whereas analysing extremes by case-control design had superior power even for much smaller sample sizes. Two real data examples are provided to support our theoretical findings and to explore our mixture and parameter assumption. Conclusions: Our findings support the idea to re-analyse the available meta-analysis data sets to detect new loci in the extremes. Moreover, our investigation offers an explanation for discrepant findings when analysing quantitative traits in the general population and in the extremes. Copyright (C) 2011 S. Karger AG, Base

Engineering the substrate scope of the Fe(II) dependent halogenase WelO15

Selective halogenation is an important reaction for late-stage functionalisation of drug-like molecules. Performing halogenations under mild conditions using sodium chloride as the chlorine source has great potential for sustainable catalysis. The discovery of non-heme iron (NHI) and 2-oxoglutarate dependent halogenases, acting directly on a small organic molecule and not on acyl-carrier bound substrates,[1,2] has eliminated a major drawback of know NHI-halogenases. Hence, these enzymes represent attractive starting points for developing biocatalytic routs for selective, aliphatic chlorination, a paramount challenge in organic synthesis. The wild-types have a narrow natural substrate-scope and are unexplored for biocatalytic applications.[3] After solving the crystal structure of WelO15 from Westiella intricata, we used directed evolution to redesign the active site using a small-but-smart amino acid alphabet, thereby limiting the screening effort to a HPLC compatible throughput. New variants were found, able to chlorinate novel synthesized non-natural substrates. This study represents a first step towards milder, selective chlorination using biocatalysis. Please click Additional Files below to see the full abstract

Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification: A Euro-CCAD study.

Background and aimsAlthough much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score.MethodsFrom the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CT scanning for CAC scoring.ResultsAmong all patients, male sex (OR = 4.85, p<0.001) and diabetes (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p<0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively.ConclusionIn addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes

Coronary age as a risk factor in the modified Framingham risk score

BACKGROUND: Clinical guidelines emphasize risk assessment as vital to patient selection for medical primary intervention. However, risk assessment methods are restricted in their ability to predict further coronary events. The most widely accepted tool in the United States is the Framingham risk score. In these equations age is a powerful risk factor. Although the extent of coronary atherosclerosis increases with age, there is large inter-individual variability in the rate of development and progression of this disease. This fact limits the utility of Framingham scoring when applied to individuals. Electron beam tomography (EBT), which measures coronary calcium, provides a non-invasive method for assessing coronary plaque burden, thus offering the possibility of providing a more accurate estimate of an individual's "arterial age" than from chronological age alone. METHODS: In this paper we discuss a new and simple method for incorporating the coronary calcium score (CCS) to modify the Framingham Risk Assessment (FRA). Using this method, a coronary artery calcium (CAC) age equivalent is generated that replaces chronological age in Framingham scoring. RESULTS AND DISCUSSION: Using a percentile table of CCS scores by age group and sex, individuals are matched to the age group whose calcium score most closely approximates their own individual score. The original 10-year absolute risk score of a 65-year old man with a CCS of 6 based on chronological age is 10%, whereas the modified absolute risk score based on CAC age equivalents is 2%. CONCLUSION: Our approach of replacing chronological age with CAC age equivalents in the Framingham equations possesses simplicity of application combined with precision. Physicians can easily derive adjusted Framingham risk scores and prescribe intervention methods based on patients' ten-year risks. The adjusted ten-year risks are likely to be more accurate than unadjusted risks since they are based on coronary calcium score information. The modified FRA approach not only may increase the predicted risk for some patients, but also may decrease the predicted risk for others, making it a more precise adjustment than other methods

Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR)

AIMS: Modern imaging technology allows us the visualization of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis. The prevalence, quantity, and risk factors for CAC were compared between two studies with similar imaging protocols but different source populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR). METHODS AND RESULTS: The measured CAC in 2220 MESA participants were compared with those in 3,126 HNR participants with the inclusion criteria such as age 45-75 years, Caucasian race, and free of baseline cardiovascular disease. Despite similar mean levels of CAC of 244.6 among participants in MESA and of 240.3 in HNR (P = 0.91), the prevalence of CAC > 0 was lower in MESA (52.6%) compared with HNR (67.0%) with a prevalence rate ratio of CAC > 0 of 0.78 [95% confidence interval (CI): 0.72-0.85] after adjustment for known risk factors. Consequently, among participants with CAC > 0, the participants in MESA tended to have higher levels of CAC than those in HNR (ratio of CAC levels: 1.39; 95% CI: 1.19-1.63), since many HNR participants have small (near zero) CAC values. CONCLUSIONS: The CAC prevalence was lower in the United States (MESA) cohort than in the German (HNR) cohort, which may be explained by more favourable risk factor levels among the MESA participants. The predictors for increased levels of CAC were, however, similar in both cohorts with the exception that male gender, blood pressure, and body mass index were more strongly associated in the HNR cohort

Secondhand Smoke Exposure and Coronary Artery Calcification among Nonsmoking Participants of a Population-Based Cohort

Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis

Impact of atherosclerotic plaque composition on coronary microembolization during percutaneous coronary interventions

BACKGROUND: Cardiac marker release after percutaneous coronary interventions (PCI) reflects myocardial necrosis which is usually the result of periprocedural (micro)embolization of atherothrombotic debris and associated with impaired left ventricular function and adverse outcome. METHODS: In this prospective study, we examined 55 patients treated by direct stenting of single de-novo lesions to assess the relationship between plaque composition, as determined by preinterventional intravascular ultrasound (IVUS) with radiofrequency data (IVUS-RF) analysis (so-called Virtual Histology) versus coronary microembolization, as determined by serial measurement of cardiac markers. IVUS was performed with an electronic system and 20-MHz IVUS catheters. Serum creatine kinase (CK) and cardiac troponin I (CTnI) were determined before PCI and after 6, 12, and 24 hours. RESULTS: Plaques had a volume of 99 +/- 63 mm(3) and were composed of fibrous (61 +/- 9%) and fibro-fatty tissue (27 +/- 12%), dense calcium (4 +/- 3%), and necrotic core (NC) (8 +/- 6%). NC volume per se, volume per 10 mm of segment length, and volume % were correlated (r = 0.64, 0.66, and 0.52 respectively; all P 10.8 mm(3)) had a particularly high increase in markers (P < 0.001). In contrast, total plaque volume and plaque components other than NC had no relation with cardiac markers (ns). CONCLUSIONS: Patients with large NC in culprit lesions may experience more myocardial injury from peri-interventional microembolization. IVUS-RF assessment before PCI has the potential to identify lesions at particular high risk which may help to tailor PCI

Progression of coronary calcification in healthy postmenopausal women

BACKGROUND: Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women. METHODS: We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score ≥10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans. RESULTS: Mean age of study participants was 65 ± 9 years (mean ± SD), body mass index was 26.1 ± 6.1 kg/m(2), and baseline calcium score was 162 ± 220 Agatston units. Mean interval between scans was 3.3 ± 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification. CONCLUSION: Among postmenopausal women with coronary calcium score ≥ 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score