270 research outputs found
Genetic variation in telomere maintenance genes in relation to ovarian cancer survival
Telomeres are repetitive non-coding DNA sequences at the ends of chromosomes that provide protection against chromosomal instability. Telomere length and stability are influenced by proteins, including telomerase which is partially encoded by the TERT gene. Genetic variation in the TERT gene is associated with ovarian cancer risk, and predicts survival in lung cancer and glioma. We investigated whether genetic variation in five telomere maintenance genes was associated with survival among 1480 cases of invasive epithelial ovarian cancer in the population-based New England Case-Control Study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals. Overall we observed no significant associations between SNPs in telomere maintenance genes and mortality using a significance threshold of p=0.001. However, we observed some suggestive associations in subgroup analyses. Future studies with larger populations may further our understanding of what role telomeres play in ovarian cancer survival
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Genetic variation in telomere maintenance genes in relation to ovarian cancer survival
Telomeres are repetitive non-coding DNA sequences at the ends of chromosomes that provide protection against chromosomal instability. Telomere length and stability are influenced by proteins, including telomerase which is partially encoded by the TERT gene. Genetic variation in the TERT gene is associated with ovarian cancer risk, and predicts survival in lung cancer and glioma. We investigated whether genetic variation in five telomere maintenance genes was associated with survival among 1480 cases of invasive epithelial ovarian cancer in the population-based New England Case-Control Study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals. Overall we observed no significant associations between SNPs in telomere maintenance genes and mortality using a significance threshold of p=0.001. However, we observed some suggestive associations in subgroup analyses. Future studies with larger populations may further our understanding of what role telomeres play in ovarian cancer survival
Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin- Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health- System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154898/1/phar2376.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154898/2/phar2376_am.pd
New Generation of Educators Initiative: Transforming teacher preparation.
The focus of the New Generation of Educators Initiative (NGEI) was to answer the question "What would it take to transform teacher education?" From 2016 to 2019, with support from the S. D. Bechtel, Jr. Foundation, teacher education programs at 10 California State University (CSU) campuses partnered with local school districts to design and demonstrate innovative practices that could transform teacher preparation. This report documents the learnings from multiple participants in this transformative work, including Foundation program staff and representatives from partnerships between universities and school districts
Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations
The widespread introduction of artemisinin-based combination therapy has contributed to
recent reductions in malaria mortality. Combination therapies have a range of advantages,
including synergism, toxicity reduction, and delaying the onset of resistance acquisition.
Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of
effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we
have previously employed drug-repositioning to identify the anti-amoebic drug, emetine
dihydrochloride hydrate, as a potential candidate for repositioned use against malaria.
Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with
its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited
by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner
drug would present an opportunity for dose-reduction, thus increasing the therapeutic window.
The lack of reliable and standardised methodology to enable the in vitro definition of
synergistic potential for antimalarials is a major drawback. Here we use isobologram and
combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define
drug interactivity in an objective, automated manner. The method, based on the median
effect principle proposed by Chou and Talalay, was initially validated for antimalarial application
using the known synergistic combination (atovaquone-proguanil). The combination was
used to further understand the relationship between SYBR Green viability and cytocidal versus
cytostatic effects of drugs at higher levels of inhibition. We report here the use of the
optimised Chou Talalay method to define synergistic antimalarial drug interactivity between
emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential
route to harness the nanomolar antimalarial efficacy of this affordable natural product
Recapturing the Power of Ritual to Enhance Community in Aging
Ritual returns us to the center of who we are. In times of transition, loss, disconnection, and loneliness, ritual offers transformative power. It can provide a language for expression, stability, serve an integrating force in community, mediate tradition, and offer emotional support. This article explores the need for ritual in coping with late life changes, the relationship of ritual to suffering, value of ritual in storytelling and mourning, and explains the role of witness facilitated through community. Therapeutic functions of ritual are addressed and a framework for ritual design is suggested
Volatility in the Housing Market: Evidence on Risk and Return in the London Sub-market
The impact of volatility in housing market analysis is reconsidered via examination of the risk-return relationship in the London housing market is examined. In addition to providing the first empirical results for the relationship between risk (as measured by volatility) and returns for this submarket, the analysis offers a more general message to empiricists via a detailed and explicit evaluation of the impact of empirical design decisions upon inferences. In particular, the negative risk-return relationship discussed frequently in the housing market literature is examined and shown to depend upon typically overlooked decisions concerning components of the empirical framework from which statistical inferences are drawn
Diagnosis of Partial Body Radiation Exposure in Mice Using Peripheral Blood Gene Expression Profiles
In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB) can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI). However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79–100%) compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16–43%), suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation
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