Fluid balance and cardiac function in septic shock as predictors of hospital mortality

INTRODUCTION: Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled. RESULTS: A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome. CONCLUSIONS: Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude

Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Understanding the Possible Impact of a Community Service Learning Experience during University on Career Development

This is the final, published PDF of an article published by the Canadian Journal of Career development in 2011 and reproduces with permission from the publisher. The full issue is available online at: http://cjcdonline.ca/download/vol-18-issue-1/There is general consensus that volunteer and community servicelearning (CSL) experiences are important to career development even though research remains unclear on the relationship and about how best to help students make a link between service and career decisions. This study investigated the possible impact of CSL experiences on students’ career development among a sample of Canadian university students. Interviews were conducted with students (N = 36) who had completed a CSL component in one or more psychology courses. Responses revealed that there are many factors and stakeholders involved in the relationship between a service-learning experience and career thinking, and different aspects of the experience can affect career choice in different ways. It was also found that students’ responses in personal interviews did not always match up with prior responses on a closed-ended survey; 68% gave consistent responses in both the survey and interviews, whereas 26% gave inconsistent responses and all of these participants had initially reported no impact on a survey and then later discussed in interviews how CSL had confirmed a career choice. Further analysis of interview data found a connection between CSL and career thinking either towards or away from confirming a career choice and the type of impact varied by four characteristics: (1) the number of placements, (2) reflection assignments and activities, (3) emotional engagement, and (4) matching/degree of fit between the placement setting and a student’s expectations for the placement. A subsequent review of the Campus Compact course syllabi web database of 50 disciplines showed that 8% of syllabi explicitly address work, career, or job issues and these syllabi provide useful examples of reflection questions for linking the service-learning experience to career development. An important implication for assessing student CSL outcomes is that asking students one direct, closed-ended question to reflect on how a CSL placement has affected career thinking is too simplistic. Our findings may explain the inconclusive and unexpected findings of past research and guide career counsellors and teachers in facilitating reflections that foster student career development.This research was made possible through internal and external funding fromWilfrid Laurier Research office (funded by SSHRC—Social Sciences and Humanities Research Council) and the J.W. McConnell Family Foundation Montreal, Canada

Understanding the possible impact of a community service learning experience during university on career development

This is the final, published PDF of an article published by the Canadian Journal of Career development in 2011 and reproduces with permission from the publisher. The full issue is available online at: http://cjcdonline.ca/download/vol-18-issue-1/There is general consensus that volunteer and community servicelearning (CSL) experiences are important to career development even though research remains unclear on the relationship and about how best to help students make a link between service and career decisions. This study investigated the possible impact of CSL experiences on students’ career development among a sample of Canadian university students. Interviews were conducted with students (N = 36) who had completed a CSL component in one or more psychology courses. Responses revealed that there are many factors and stakeholders involved in the relationship between a service-learning experience and career thinking, and different aspects of the experience can affect career choice in different ways. It was also found that students’ responses in personal interviews did not always match up with prior responses on a closed-ended survey; 68% gave consistent responses in both the survey and interviews, whereas 26% gave inconsistent responses and all of these participants had initially reported no impact on a survey and then later discussed in interviews how CSL had confirmed a career choice. Further analysis of interview data found a connection between CSL and career thinking either towards or away from confirming a career choice and the type of impact varied by four characteristics: (1) the number of placements, (2) reflection assignments and activities, (3) emotional engagement, and (4) matching/degree of fit between the placement setting and a student’s expectations for the placement. A subsequent review of the Campus Compact course syllabi web database of 50 disciplines showed that 8% of syllabi explicitly address work, career, or job issues and these syllabi provide useful examples of reflection questions for linking the service-learning experience to career development. An important implication for assessing student CSL outcomes is that asking students one direct, closed-ended question to reflect on how a CSL placement has affected career thinking is too simplistic. Our findings may explain the inconclusive and unexpected findings of past research and guide career counsellors and teachers in facilitating reflections that foster student career development.This research was made possible through internal and external funding fromWilfrid Laurier Research office (funded by SSHRC—Social Sciences and Humanities Research Council) and the J.W. McConnell Family Foundation Montreal, Canada