191 research outputs found

    Comparative career accomplishments of two decades of women and men doctoral graduates in education

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    Patterns of doctoral study and subsequent career progress were compared for 756 men and women doctoral graduates in education at a research university from two six-year periods, one before and one after a rapid nation-wide increase in the percentage of women doctorates. Despite advantages relative to men in admission, financial support and full-time study, women doctorates of both periods had achieved less career progress than men but held similarly positive perceptions concerning career impact of the degree. Work experience prior to doctoral study strongly predicted career progress for both genders. Thus, affirmative action may have positively affected the careers of recent women doctorates who were younger and who began study with less established careers than women doctorates prior to 1970.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43594/1/11162_2004_Article_BF00974052.pd

    Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX)

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    In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3–10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)—independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups

    Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance.

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    BACKGROUND: Understanding mechanisms underlying specific chemotherapeutic responses in subtypes of cancer may improve identification of treatment strategies most likely to benefit particular patients. For example, triple-negative breast cancer (TNBC) patients have variable response to the chemotherapeutic agent cisplatin. Understanding the basis of treatment response in cancer subtypes will lead to more informed decisions about selection of treatment strategies. METHODS: In this study we used an integrative functional genomics approach to investigate the molecular mechanisms underlying known cisplatin-response differences among subtypes of TNBC. To identify changes in gene expression that could explain mechanisms of resistance, we examined 102 evolutionarily conserved cisplatin-associated genes, evaluating their differential expression in the cisplatin-sensitive, basal-like 1 (BL1) and basal-like 2 (BL2) subtypes, and the two cisplatin-resistant, luminal androgen receptor (LAR) and mesenchymal (M) subtypes of TNBC. RESULTS: We found 20 genes that were differentially expressed in at least one subtype. Fifteen of the 20 genes are associated with cell death and are distributed among all TNBC subtypes. The less cisplatin-responsive LAR and M TNBC subtypes show different regulation of 13 genes compared to the more sensitive BL1 and BL2 subtypes. These 13 genes identify a variety of cisplatin-resistance mechanisms including increased transport and detoxification of cisplatin, and mis-regulation of the epithelial to mesenchymal transition. CONCLUSIONS: We identified gene signatures in resistant TNBC subtypes indicative of mechanisms of cisplatin. Our results indicate that response to cisplatin in TNBC has a complex foundation based on impact of treatment on distinct cellular pathways. We find that examination of expression data in the context of heterogeneous data such as drug-gene interactions leads to a better understanding of mechanisms at work in cancer therapy response

    Validation of World Health Organisation HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda

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    IntroductionThe WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3).ObjectiveTo validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda.ResultsData was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2.ConclusionThe WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda

    Faculty roles and role preferences in ten fields of professional study

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    Teaching faculty in ten entry-level professional fields reported varying amounts of time devoted to teaching, research, consulting, and professional practice but did not differ in time devoted to administration. The faculty member's own role view was most closely related to time use, but for time spent in teaching and research, faculty age and institutional type (but not gender) were also significant predictors. Even after several general demographic characteristics and environmental variables that potentially differentiate professional from discipline-based faculty are taken into account, different professional fields may be characterized by group climates which influence or reinforce certain faculty roles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43598/1/11162_2004_Article_BF00991875.pd

    Faculty and administrator views of influences on professional programs

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    Administrators in professional programs perceive influences on the program from within the university as stronger than do faculty but the two groups do not perceive the strength of societal influences, professional community influences, or internal levels of curriculum debate differently. After controlling for program and institutional sizes and institutional types, these differences between faculty and administrator views regarding relationships between the program and the university appear characteristic of certain professional fields. The analysis was based on subsamples drawn from a data base of survey responses from 873 administrators and 849 faculty members in ten professional fields representing 732 programs in 346 colleges and universities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43601/1/11162_2004_Article_BF00992306.pd

    El Conocimiento DidĂĄctico del Contenido en ciencias: estado de la cuestiĂłn

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    This paper gives a descriptive overview of the literature related to Pedagogical Content Knowledge - PCK - in the sciences. It is expected that this review can contribute to a better understanding of PCK, pointing out what has been investigated about this concept. Specifically, we analyze: a) how PCK is defined, what are its main features and how it has been appropriated by teachers; b) the relationship between PCK, knowledge of the contents to be taught and students learning; c) how PCK was actually used in teachers' training and teachers' evaluation; and, d) the scientific areas in which PCK has been studied. It concludes that PCK is an essential tool for improving the quality of teacher training

    Faculty reflect on course planning

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    Faculty members' beliefs about educational purpose and the nature of their academic fields strongly influence how they plan introductory courses. Interviews with 89 faculty members teaching in diverse colleges and representing eight fields also identified faculty attention to student preparation, available textbooks, and locally important factors, but little attention to alternative instructional strategies during course planning. Based on the findings, the authors have developed a tentative general model of course design and related questions to guide future study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43602/1/11162_2004_Article_BF00992924.pd

    Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

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    This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∌38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio
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