Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in Relation to Ovarian Cancer Risk and Survival

Objective: To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival. Methods: We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models. Results: Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset. Conclusion: This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted

Detection of prions in the faeces of sheep naturally infected with classical scrapie

Classical scrapie is a naturally transmitted prion disease of sheep and goats. Contaminated environments may contribute to the spread of disease and evidence from animal models has implicated urine, blood, saliva, placenta and faeces as possible sources of the infection. Here we sought to determine whether sheep naturally infected with classical scrapie shed prions in their faeces. We used serial protein misfolding cyclic amplification (sPMCA) along with two extraction methods to examine faeces from sheep during both the clinical and preclinical phases of the disease and showed amplification of PrPSc in 7 of 15 and 14 of 14 sheep respectively. However PrPSc was not amplified from the faeces of 25 sheep not exposed to scrapie. These data represent the first demonstration of prion shedding in faeces from a naturally infected host and thus a likely source of prion contamination in the environment

An introduction to Trends in Extreme Weather and Climate Events: Observations, Socioeconomic Impacts, Terrestrial Ecological Impacts, and Model Projections

Weather and climatic extremes can have serious and damaging effects on human society and infrastructure as well as on ecosystems and wildlife. Thus, they are usually the main focus of attention of the news media in reports on climate. There are some indications from observations concerning how climatic extremes may have changed in the past. Climate models show how they could change in the future either due to natural climate fluctuations or under conditions of greenhouse gas-induced warming. These observed and modeled changes relate directly to the understanding of socioeconomic and ecological impacts related to extremes.Integrative Biolog

Discerning Applicants\u27 Interests in Rural Medicine: A Textual Analysis of Admission Essays

BACKGROUND: Despite efforts to construct targeted medical school admission processes using applicant-level correlates of future practice location, accurately gauging applicants\u27 interests in rural medicine remains an imperfect science. This study explores the usefulness of textual analysis to identify rural-oriented themes and values underlying applicants\u27 open-ended responses to admission essays. METHODS: The study population consisted of 75 applicants to the Rural Physician Leadership Program (RPLP) at the University of Kentucky College of Medicine. Using WordStat, a proprietary text analysis program, applicants\u27 American Medical College Application Service personal statement and an admission essay written at the time of interview were searched for predefined keywords and phrases reflecting rural medical values. From these text searches, derived scores were then examined relative to interviewers\u27 subjective ratings of applicants\u27 overall acceptability for admission to the RPLP program and likelihood of practicing in a rural area. RESULTS: The two interviewer-assigned ratings of likelihood of rural practice and overall acceptability were significantly related. A statistically significant relationship was also found between the rural medical values scores and estimated likelihood of rural practice. However, there was no association between rural medical values scores and subjective ratings of applicant acceptability. CONCLUSIONS: That applicants\u27 rural values in admission essays were not related to interviewers\u27 overall acceptability ratings indicates that other factors played a role in the interviewers\u27 assessments of applicants\u27 acceptability for admission

Middle Preclassic Period Maya Greenstone Triangulates : Forms, Contexts, and Geology of a Unique Mesoamerican Groundstone Artifact Type

Over the past twenty years our understanding of the Middle Preclassic (900–300 BCE) period has become much clearer through archaeological investigations at a number of sites located in the Upper Belize River Valley region of the eastern Maya Lowlands. While the picture of Middle Preclassic Maya life, including their material culture, has sharpened, there are aspects that remain uninvestigated. One artifact type, identified as greenstone triangulates, has been found at several Belize Valley sites and in a variety of contexts. Although a number of these multifaceted, polished groundstone items have been recovered, little research has focused on their distribution and function in the archaeological record. An evaluation of these items from primary contexts provides data for determining how they were used in daily social and/or ritual activities throughout the lowlands. Comparative data from other regions of Mesoamerica are also discussed. A detailed geological and petrographic pilot study of a sample of greenstone triangulates is provided, pointing conclusively to early, long-distance and complex exchange networks in exotic raw materials

Gender Diferences in Heart Failure Self-Care: A Multinational Cross-Sectional Study

Background Despite a common view that women are better at self-care, there is very little evidence to support or challenge this perspective in the heart failure (HF) population. Objective The purpose of this study was to determine if there are cross-cultural gender differences in self-reported HF self-care and to describe gender differences in the determinants of HF self-care. Design, setting, and participants A secondary analysis was completed of cross-sectional study data collected on 2082 adults with chronic HF from the United States, Australia and Thailand. Methods Comparisons were made between men and women regarding self-care maintenance, management and confidence as assessed by the Self-Care of Heart Failure Index, as well as the proportion of subjects engaged in adequate self-care. Multivariate comparisons were made to determine if gender explained sufficient variance in HF self-care and the likelihood of reporting adequate self-care, controlling for nine model covariates. Results The sample was comprised of 1306 men and 776 women. Most (73.5%) had systolic or mixed systolic and diastolic HF and 45% had New York Heart Association class III or IV HF. Although small and clinically insignificant gender differences were found in self-care maintenance, gender was not a determinant of any aspect of HF self-care in multivariate models. Married women were 37% less likely to report adequate self-care maintenance than unmarried women. Comorbidities only influenced the HF self-care of men. Being newly diagnosed with HF also primarily affected men. Patients with diastolic HF (predominantly women) had poorer self-care maintenance and less confidence in self-care. Conclusion Differences in HF self-care are attributable to factors other than gender; however, there are several gender-specific determinants of HF self-care that help identify patients at risk for practicing poor self-care

Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial anti-proliferative effects of calcium and vitamin D. Using data from the New England case-control study (1909 cases; 1989 controls) we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes, and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios and 95% confidence intervals. In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium (Quartile 4 (Q4, >1319 mg/day) vs. Quartile 1 (Q1, 559 IU/day vs. Q1, <164 IU/day, OR=0.51, 95% CI=0.34–0.76) and endometrioid tumors (Q4 vs. Q1, OR=0.55, 95% CI=0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk, or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium, and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation

MTHFR polymorphisms in relation to ovarian cancer risk

Objective Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. Methods We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses’ Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). Results Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T ptrend = 0.59 and A1298C ptrend = 0.58). Significant associations (C677T ptrend=0.001, A1298C ptrend=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. Conclusions MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings

Anomalous Workfunction Anisotropy in Ternary Acetylides

Anomalous anisotropy of workfunction values in ternary alkali metal transition metal acetylides is reported. Workfunction values of some characteristic surfaces in these emerging semiconducting materials may differ by more than $\approx$ 2 eV as predicted by Density Functional Theory calculations. This large anisotropy is a consequence of the relative orientation of rod-like [MC$_{2}$]$_{\infty}$ negatively charged polymeric subunits and the surfaces, with M being a transition metal or metalloid element and C$_{2}$ refers to the acetylide ion C$_{2}^{2-}$, with the rods embedded into an alkali cation matrix. It is shown that the conversion of the seasoned Cs$_{2}$Te photo-emissive material to ternary acetylide Cs$_{2}$TeC$_{2}$ results in substantial reduction of its $\approx$ 3 eV workfunction down to 1.71-2.44 eV on the Cs$_{2}$TeC$_{2}$(010) surface while its high quantum yield is preserved. Similar low workfunction values are predicted for other ternary acetylides as well, allowing for a broad range of applications from improved electron- and light-sources to solar cells, field emission displays, detectors and scanners.Comment: Accepted for publication in Phys. Rev.