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The safety and health improvement:enhancing law enforcement departments study: feasibility and findings

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This randomized prospective trial aimed to assess the feasibility and efficacy of a team-based worksite health and safety intervention for law enforcement personnel. Four-hundred and eight subjects were enrolled and

This randomized prospective trial aimed to assess the feasibility and efficacy of a team-based worksite health and safety intervention for law enforcement personnel. Four-hundred and eight subjects were enrolled and half were randomized to meet for weekly, peer-led sessions delivered from a scripted team-based health and safety curriculum. Curriculum addressed: exercise, nutrition, stress, sleep, body weight, injury, and other unhealthy lifestyle behaviors such as smoking and heavy alcohol use. Health and safety questionnaires administered before and after the intervention found significant improvements for increased fruit and vegetable consumption, overall healthy eating, increased sleep quantity and sleep quality, and reduced personal stress.

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Date Created
  • 2014-05-08

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Ancient Genes Establish Stress-Induced Mutation as a Hallmark of Cancer

Description

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts.

We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to stress that evolved among prokaryotes was co-opted to maintain diversity in the germline and immune system, while the original phenotype is restored in cancer. Reversion to a stress-induced mutational response is a hallmark of cancer that allows for effectively searching “protected” genome space where genes causally implicated in cancer are located and underlies the high adaptive potential and concomitant therapeutic resistance that is characteristic of cancer.

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Created

Date Created
  • 2017-04-25

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Obtaining accurate estimates of the mediated effect with and without prior information

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Research methods based on the frequentist philosophy use prior information in a priori power calculations and when determining the necessary sample size for the detection of an effect, but not

Research methods based on the frequentist philosophy use prior information in a priori power calculations and when determining the necessary sample size for the detection of an effect, but not in statistical analyses. Bayesian methods incorporate prior knowledge into the statistical analysis in the form of a prior distribution. When prior information about a relationship is available, the estimates obtained could differ drastically depending on the choice of Bayesian or frequentist method. Study 1 in this project compared the performance of five methods for obtaining interval estimates of the mediated effect in terms of coverage, Type I error rate, empirical power, interval imbalance, and interval width at N = 20, 40, 60, 100 and 500. In Study 1, Bayesian methods with informative prior distributions performed almost identically to Bayesian methods with diffuse prior distributions, and had more power than normal theory confidence limits, lower Type I error rates than the percentile bootstrap, and coverage, interval width, and imbalance comparable to normal theory, percentile bootstrap, and the bias-corrected bootstrap confidence limits. Study 2 evaluated if a Bayesian method with true parameter values as prior information outperforms the other methods. The findings indicate that with true values of parameters as the prior information, Bayesian credibility intervals with informative prior distributions have more power, less imbalance, and narrower intervals than Bayesian credibility intervals with diffuse prior distributions, normal theory, percentile bootstrap, and bias-corrected bootstrap confidence limits. Study 3 examined how much power increases when increasing the precision of the prior distribution by a factor of ten for either the action or the conceptual path in mediation analysis. Power generally increases with increases in precision but there are many sample size and parameter value combinations where precision increases by a factor of 10 do not lead to substantial increases in power.

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Created

Date Created
  • 2014