48 research outputs found

    A Note on a Conjecture of Watanabe and Yoshida

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    We consider a conjecture of Watanabe and Yoshida concerning the Hilbert - Kunz multiplicity of an ideal in a Cohen-Macaulay ring and provide a proof of the conjecture in the case the ring is graded.Comment: 6 page

    Facilitating LOS Debriefings: A Training Manual

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    This manual is a practical guide to help airline instructors effectively facilitate debriefings of Line Oriented Simulations (LOS). It is based on a recently completed study of Line Oriented Flight Training (LOFT) debriefings at several U.S. airlines. This manual presents specific facilitation tools instructors can use to achieve debriefing objectives. The approach of the manual is to be flexible so it can be tailored to the individual needs of each airline. Part One clarifies the purpose and objectives of facilitation in the LOS setting. Part Two provides recommendations for clarifying roles and expectations and presents a model for organizing discussion. Part Tree suggests techniques for eliciting active crew participation and in-depth analysis and evaluation. Finally, in Part Four, these techniques are organized according to the facilitation model. Examples of how to effectively use the techniques are provided throughout, including strategies to try when the debriefing objectives are not being fully achieved

    LOFT Debriefings: An Analysis of Instructor Techniques and Crew Participation

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    This study analyzes techniques instructors use to facilitate crew analysis and evaluation of their Line-Oriented Flight Training (LOFT) performance. A rating instrument called the Debriefing Assessment Battery (DAB) was developed which enables raters to reliably assess instructor facilitation techniques and characterize crew participation. Thirty-six debriefing sessions conducted at five U.S. airlines were analyzed to determine the nature of instructor facilitation and crew participation. Ratings obtained using the DAB corresponded closely with descriptive measures of instructor and crew performance. The data provide empirical evidence that facilitation can be an effective tool for increasing the depth of crew participation and self-analysis of CRM performance. Instructor facilitation skill varied dramatically, suggesting a need for more concrete hands-on training in facilitation techniques. Crews were responsive but fell short of actively leading their own debriefings. Ways to improve debriefing effectiveness are suggested

    How Thoroughly Do Proposed Nextgen Mid-Term Operational Improvements Address Existing Threats?

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    The goals of the Federal Aviation Administration’s (FAA) Next Generation Air Transportation System (NextGen) include improved safety, increased capacity, increased efficiency, and reduced environmental impact. The FAA has developed 46 mid-term Operational Improvements (OIs) to facilitate initial realization of these benefits in the 2015 – 2018 timeframe. These OIs describe changes in technologies, policies and procedures from current-day air and ground operations designed to mitigate safety, capacity, efficiency, and environmental issues. The main goal of this project was to investigate how thoroughly threats to safety present in today’s operations are addressed by the OIs. These threats, without mitigation, could remain threats in the mid-term, potentially compromising the intended NextGen safety benefits. To address this concern, we extracted threats to safety from 200 Aviation Safety Reporting System incident reports filed by tower air traffic controllers over a five-year period. We then evaluated whether these threats are addressed by the mid-term OIs

    Corrigendum: Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis

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    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn’s nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a “sensory network” and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome

    The Problematization of Sexuality among Women Living with HIV and a New Feminist Approach for Understanding and Enhancing Women’s Sexual Lives

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    In the context of HIV, women’s sexual rights and sexual autonomy are important but frequently overlooked and violated. Guided by community voices, feminist theories, and qualitative empirical research, we reviewed two decades of global quantitative research on sexuality among women living with HIV. In the 32 studies we found, conducted in 25 countries and composed mostly of cis-gender heterosexual women, sexuality was narrowly constructed as sexual behaviours involving risk (namely, penetration) and physiological dysfunctions relating to HIV illness, with far less attention given to the fullness of sexual lives in context, including more positive and rewarding experiences such as satisfaction and pleasure. Findings suggest that women experience declines in sexual activity, function, satisfaction, and pleasure following HIV diagnosis, at least for some period. The extent of such declines, however, is varied, with numerous contextual forces shaping women’s sexual well-being. Clinical markers of HIV (e.g., viral load, CD4 cell count) poorly predicted sexual outcomes, interrupting widely held assumptions about sexuality for women with HIV. Instead, the effects of HIV-related stigma intersecting with inequities related to trauma, violence, intimate relations, substance use, poverty, aging, and other social and cultural conditions primarily influenced the ways in which women experienced and enacted their sexuality. However, studies framed through a medical lens tended to pathologize outcomes as individual “problems,” whereas others driven by a public health agenda remained primarily preoccupied with protecting the public from HIV. In light of these findings, we present a new feminist approach for research, policy, and practice toward understanding and enhancing women’s sexual lives—one that affirms sexual diversity; engages deeply with society, politics, and history; and is grounded in women’s sexual rights

    Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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    In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

    Germline variation at 8q24 and prostate cancer risk in men of European ancestry

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    Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

    Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery of 187 Novel Risk Variants

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    The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups

    Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

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    Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe
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