303 research outputs found

    Sir William Osler, M.D., C.M.

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    Sir William Osler impacted medical education and the practice of medicine like few other physicians. As a writer, he authored nearly 1500 publications and lent his name to numerous eponyms. As a teacher he educated vast numbers of students and through his legacy impacted countless more. Sir William Osler (Fig. 1) epitomized what a physician should be throughout his professional life

    James Marion Sims, M.D., LL.D.

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    Few physicians have been as celebrated and loathed as James Marion Sims, M.D., LL.D. Dr. Sims’ modest early life and education never could have predicted that he would one day be called the ‘‘Father of American Gynecology.’’1, 2 Lauded by contemporaries and early historians as ‘‘one of the most original and gifted of American surgeons,’’ he performed the first successful operation to correct vesicovaginal fistulas (a condition that prior to 1852 was known as the ‘‘stumbling-block of gynecology’’).1 Today, the same work that earned Dr. Sims fame, fortune, and innumerable honors has been called into question, because of the unethical manner in which he developed his surgical innovation

    A Sub-Type of Familial Pancreatic Cancer: Evidence and Implications of Loss-of-Function Polymorphisms in Indoleamine-2,3-Dioxygenase-2.

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    BACKGROUND: Variation in an individual\u27s genetic status can impact the development of pancreatic ductal adenocarcinoma; however, the majority of familial pancreatic cancers (FPC) cannot yet be attributed to a specific inherited mutation. We present data suggesting a correlation between loss-of-function single nucleotide polymorphisms (SNPs) in an immune regulator gene, indoleamine-2,3-dioxygenase-2 (IDO2), and an increased risk of FPC. STUDY DESIGN: Germline DNA from patients who underwent resection for pancreatic ductal adenocarcinoma (n = 79) was sequenced for the IDO2 SNPs R248W and Y359Stop. Genotypes resulting in inactivation of IDO2 (Y325X homozygous, R248W homozygous) were labeled as homozygous, and the other genotypes were grouped as wild-type or heterozygous. Genotype distributions of each SNP were analyzed for Hardy-Weinberg deviation. A genotype frequency set from the 1000 Genomes Project (n = 99) was used as a genetic control for genotype distribution comparisons. RESULTS: A significant 2-fold increase in the overall prevalence of the Y359Stop homozygous genotype compared with the expected Hardy-Weinberg equilibrium was noted (p \u3c 0.05). Familial pancreatic cancer was noted in 15 cases (19%) and comparison of the FPC cohort set to the genetic control set showed a 3-fold increase in Y359Stop homozygous rates (p = 0.054). Overall in our cohort, the homozygous genotype group was associated with increased risk of FPC (odds ratio 5.4; 95% CI 1.6 to 17.6; p \u3c 0.01). Sex, age at diagnosis, and history of tobacco use were not found to be significantly associated with FPC. CONCLUSIONS: Our preliminary data suggest a strong association between the IDO2 inactivating Y359Stop SNP and an increased risk of FPC when compared with the control group. Future studies will evaluate the value of IDO2 genotyping as a prognostic, early detection marker for pancreatic ductal adenocarcinoma and a predictive marker for novel immune checkpoint therapies

    Cheryl's Birthday

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    We present four logic puzzles and after that their solutions. Joseph Yeo designed 'Cheryl's Birthday'. Mike Hartley came up with a novel solution for 'One Hundred Prisoners and a Light Bulb'. Jonathan Welton designed 'A Blind Guess' and 'Abby's Birthday'. Hans van Ditmarsch and Barteld Kooi authored the puzzlebook 'One Hundred Prisoners and a Light Bulb' that contains other knowledge puzzles, and that can also be found on the webpage http://personal.us.es/hvd/lightbulb.html dedicated to the book.Comment: In Proceedings TARK 2017, arXiv:1707.0825

    An Approach for the Direct Inclusion of Weather Information in the Power Flow

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    While it is widely recognized that weather impacts the power flow, historically weather information has only been implicitly included. This paper presents an approach for the direct inclusion of weather information in the power flow. Key issues addressed by the paper include the availability of weather information, the mapping of weather information to electric grid components, a flexible and extensible modeling approach for relating weather values to the power flow models, and the visualization of the weather impacts. The approach is demonstrated on several electric grids ranging in size from 7000 to 82,000 buses using weather data over several different years

    Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: Can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

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    Background: Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient’s health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects. Methods: A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction. Results: Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatmentrelated symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancerspecific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options