222 research outputs found

    Cost Should Be No Barrier: An Evaluation of the First Year of Harvard's Financial Aid Initiative

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    This paper evaluates the first year of Harvard's Financial Aid Initiative, which increased aid and recruiting for students from low income backgrounds. Using rich data from the Census and administrative sources, we estimate family incomes for the vast major of plausible applicants from the U.S. We find that the Initiative had a significant effect almost entirely because it attracted a pool of applicants that was larger and slightly poorer. It appears that very similar standards of admission were used for this group as had been used in previous years. This group, once admitted, enrolled at a rate very similar to that of previous years. Thus, there are a greater number of low income students in the Class of 2009 than in the Class of 2008 simply because more well-qualified, low income students applied. Many apparently qualified students still do not apply, and many of these "missing applicants" come from high schools that have little or no tradition of sending applications to selective private colleges. Targeted outreach to such "one offs" -- that is, students who are one of only a few qualified students from their school in recent years -- may be a way for selective private colleges to increase their income diversity.

    A Middle Palaeolithic to Early Upper Palaeolithic succession from an open air site at Beedings, West Sussex

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    The collection of flintwork from the site of Beedings, West Sussex (England) contains by far the largest number of stone tools from the earliest Upper Palaeolithic of Britain, and is one of the two largest assemblages of its type in Europe. Despite its obvious importance, its analysis has been hindered by several factors resulting from its early excavation. Chief amongst these is the almost total lack of stratigraphic or contextual information: its Early Upper Palaeolithic attribution has hitherto been made largely on its typological and technological similarity to stratified archaeology elsewhere.\ud \ud New fieldwork in 2007 and 2008 in an area directly adjacent to the original site located further Upper Palaeolithic material, in addition to Middle Palaeolithic and Mesolithic material, situated within a series of fissures. Here we provide an overview of the excavation and details of the archaeological context within which further flint artefacts were found. By extension this work provides the first contextual information for the old, larger collection.\ud \ud The results of OSL analysis accord with an Early Upper Palaeolithic age for the majority of the old lithic collection from the site. Stratigraphic data support this Early Upper Palaeolithic age, and also help to validate the separation of material within the old collection into Middle Palaeolithic, Early Upper Palaeolithic and Mesolithic. These stratigraphic data also suggest that Beedings is the only stratified Middle–Upper Palaeolithic open-air site in Britain. Taphonomic analysis indicates a mechanism for site formation, and accounts for the exceptional preservation of this Palaeolithic archaeology. In the light of this taphonomic analysis the “Sackung” hypothesis of site capture proposed previously for Beedings is upheld and further discussed. Wider implications for the preservation of open-air Palaeolithic sites in the region are also considered

    AGS Position Statement: Making Medical Treatment Decisions for Unbefriended Older Adults

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/1/jgs14586_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/2/jgs14586.pd

    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

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    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH(2)-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH(2)-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

    Validation of the Bluebelle Wound Healing questionnaire (WHQ) for assessment of surgical site infection in primary surgical wounds after hospital discharge

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    Background Accurate assessment of surgical‐site infection (SSI) is crucial for surveillance and research. Self‐reporting patient measures are needed because current SSI tools are limited for assessing patients after leaving hospital. The Bluebelle Wound Healing Questionnaire (WHQ) was developed for patient or observer completion; this study tested its acceptability, scale structure, reliability and validity in patients with closed primary wounds after abdominal surgery. Methods Patients completed the WHQ (self‐assessment) within 30 days after leaving hospital and returned it by post. Healthcare professionals completed the WHQ (observer assessment) by telephone or face‐to‐face. Questionnaire response rates and patient acceptability were assessed. Factor analysis and Cronbach's α examined scale structure and internal consistency. Test–retest and self‐ versus observer reliability assessments were performed. Sensitivity and specificity for SSI discrimination against a face‐to‐face reference diagnosis (using Centers for Disease Control and Prevention criteria) were examined. Results Some 561 of 792 self‐assessments (70·8 per cent) and 597 of 791 observer assessments (75·5 per cent) were completed, with few missing data or problems reported. Data supported a single‐scale structure with strong internal consistency (α greater than 0·8). Reliability between test–retest and self‐ versus observer assessments was good (κ 0·6 or above for the majority of items). Sensitivity and specificity for SSI discrimination was high (area under the receiver operating characteristic (ROC) curve 0·91). Conclusion The Bluebelle WHQ is acceptable, reliable and valid with a single‐scale structure for postdischarge patient or observer assessment of SSI in closed primary wounds

    Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

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    Background Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London
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