System Reliability: Exact Bayesian Intervals Compared With Fiducial Intervals

This paper compares numerically two different, widely used lower limit estimates for the reliability of a series system: Bayesian limits and fiducial limits. The fiducial limits are obtained by Monte Carlo simulation because of its simplicity and ease of computer programming. Subsystem failures are s-independent and exponentially distributed; life test data are available for estimating the failure rate of each system. Copyright © 1975 by The Institute of Electrical and Electronics Engineers, Inc

Bayesian Confidence Limits For The Reliability Of Mixed Cascade And Parallel Independent Exponential Subsystems

This paper deals with the theoretical problem of deriving Bayesian confidence intervals for the reliability of a system consisting of both cascade and parallel subsystems where each subsystem is independent and has an exponential failure probability density function (pdf). This approach is applicable when test data are available for each individual subsystem and not for the entire system. The Mellin integral transform is used to analyze the system in a step-by-step procedure until the posterior pdf of the system reliability is obtained. The posterior cumulative distribution function is then obtained in the usual manner by integrating the pdf, which serves the dual purpose of yielding system reliability confidence limits while at the same time providing a check on the accuracy of the derived pdf. A computer program has been written in FORTRAN IV to evaluate the confidence limits. An example is presented which uses the computer program. Copyright © 1974 by The Institute of Electrical and Electronics Engineers, Inc

Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective

This Report has a number of inter-related general purposes. One is to explore the extent to which food, nutrition, physical activity, and body composition modify the risk of cancer, and to specify which factors are most important. To the extent that environmental factors such as food, nutrition, and physical activity influence the risk of cancer, it is a preventable disease. The Report specifies recommendations based on solid evidence which, when followed, will be expected to reduce the incidence of cancer

CRTAP Is Required for Prolyl 3- Hydroxylation and Mutations Cause Recessive Osteogenesis Imperfecta

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A Pearson-Dirichlet random walk

A constrained diffusive random walk of n steps and a random flight in Rd, which can be expressed in the same terms, were investigated independently in recent papers. The n steps of the walk are identically and independently distributed random vectors of exponential length and uniform orientation. Conditioned on the sum of their lengths being equal to a given value l, closed-form expressions for the distribution of the endpoint of the walk were obtained altogether for any n for d=1, 2, 4 . Uniform distributions of the endpoint inside a ball of radius l were evidenced for a walk of three steps in 2D and of two steps in 4D. The previous walk is generalized by considering step lengths which are distributed over the unit (n-1) simplex according to a Dirichlet distribution whose parameters are all equal to q, a given positive value. The walk and the flight above correspond to q=1. For any d >= 3, there exist, for integer and half-integer values of q, two families of Pearson-Dirichlet walks which share a common property. For any n, the d components of the endpoint are jointly distributed as are the d components of a vector uniformly distributed over the surface of a hypersphere of radius l in a space Rk whose dimension k is an affine function of n for a given d. Five additional walks, with a uniform distribution of the endpoint in the inside of a ball, are found from known finite integrals of products of powers and Bessel functions of the first kind. They include four different walks in R3 and two walks in R4. Pearson-Liouville random walks, obtained by distributing the total lengths of the previous Pearson-Dirichlet walks, are finally discussed.Comment: 33 pages 1 figure, the paper includes the content of a recently submitted work together with additional results and an extended section on Pearson-Liouville random walk

Functional Characterization of CLPTM1L as a Lung Cancer Risk Candidate Gene in the 5p15.33 Locus

Cleft Lip and Palate Transmembrane Protein 1-Like (CLPTM1L), resides in a region of chromosome 5 for which copy number gain has been found to be the most frequent genetic event in the early stages of non-small cell lung cancer (NSCLC). This locus has been found by multiple genome wide association studies to be associated with lung cancer in both smokers and non-smokers. CLPTM1L has been identified as an overexpressed protein in human ovarian tumor cell lines that are resistant to cisplatin, which is the only insight thus far into the function of CLPTM1L. Here we find CLPTM1L expression to be increased in lung adenocarcinomas compared to matched normal lung tissues and in lung tumor cell lines by mechanisms not exclusive to copy number gain. Upon loss of CLPTM1L accumulation in lung tumor cells, cisplatin and camptothecin induced apoptosis were increased in direct proportion to the level of CLPTM1L knockdown. Bcl-xL accumulation was significantly decreased upon loss of CLPTM1L. Expression of exogenous Bcl-xL abolished sensitization to apoptotic killing with CLPTM1L knockdown. These results demonstrate that CLPTM1L, an overexpressed protein in lung tumor cells, protects from genotoxic stress induced apoptosis through regulation of Bcl-xL. Thus, this study implicates anti-apoptotic CLPTM1L function as a potential mechanism of susceptibility to lung tumorigenesis and resistance to chemotherapy

Actionable, Pathogenic Incidental Findings in 1,000 Participants’ Exomes

The incorporation of genomics into medicine is stimulating interest on the return of incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated the number of expected actionable findings per individual; therefore, we classified actionable pathogenic single-nucleotide variants in 500 European- and 500 African-descent participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project. The 1,000 individuals were screened for variants in 114 genes selected by an expert panel for their association with medically actionable genetic conditions possibly undiagnosed in adults. Among the 1,000 participants, 585 instances of 239 unique variants were identified as disease causing in the Human Gene Mutation Database (HGMD). The primary literature supporting the variants’ pathogenicity was reviewed. Of the identified IFs, only 16 unique autosomal-dominant variants in 17 individuals were assessed to be pathogenic or likely pathogenic, and one participant had two pathogenic variants for an autosomal-recessive disease. Furthermore, one pathogenic and four likely pathogenic variants not listed as disease causing in HGMD were identified. These data can provide an estimate of the frequency (∼3.4% for European descent and ∼1.2% for African descent) of the high-penetrance actionable pathogenic or likely pathogenic variants in adults. The 23 participants with pathogenic or likely pathogenic variants were disproportionately of European (17) versus African (6) descent. The process of classifying these variants underscores the need for a more comprehensive and diverse centralized resource to provide curated information on pathogenicity for clinical use to minimize health disparities in genomic medicine

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Colorectal cancer screening among African American church members: A qualitative and quantitative study of patient-provider communication

BACKGROUND: A healthcare provider's recommendation to undergo screening has been shown to be one of the strongest predictors of completing a colorectal cancer (CRC) screening test. We sought to determine the relationship between the general quality of self-rated patient-provider communication and the completion of CRC screening. METHODS: A formative study using qualitative data from focus groups and quantitative data from a cross-sectional survey of church members about the quality of their communication with their healthcare provider, their CRC risk knowledge, and whether they had completed CRC screening tests. Focus group participants were a convenience sample of African American church members. Participants for the survey were recruited by telephone from membership lists of 12 African American churches located in rural counties of North Carolina to participate in the WATCH (Wellness for African Americans Through Churches) Project. RESULTS: Focus Groups. Six focus groups (n = 45) were conducted prior to the baseline survey. Discussions focused on CRC knowledge, and perceived barriers/motivators to CRC screening. A theme that emerged during each groups' discussion about CRC screening was the quality of the participants' communication with their health care provider. Survey. Among the 397 participants over age 50, 31% reported CRC screening within the recommended guidelines. Participants who self-rated their communication as good were more likely to have been screened (36%) within the recommended guidelines than were participants with poor communication (17%) (OR = 2.8, 95% CI 1.2, 6.4; p = 0.013). Participants who had adequate CRC knowledge completed CRC screening at a higher rate than those with inadequate knowledge (p = 0.011). The percentage of participants with CRC screening in the recommended guidelines, stratified by communication and knowledge group were: 42% for good communication/adequate knowledge; 27% for good communication/inadequate knowledge; 29% for poor communication/adequate knowledge; and 5% for poor communication/inadequate knowledge. CONCLUSIONS: Participants who rated their patient-provider communication as good were more likely to have completed CRC screening tests than those reporting poor communication. Among participants reporting good communication, knowledge about colorectal cancer was also associated with test completion. Interventions to improve patient-provider communication may be important to increase low rates of CRC screening test completion among African Americans