679 research outputs found

    The Law and Policy of Civil Rights: A Tactical Perspective for Educators

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    This article is presented to share with fellow professional teacher-scholars the preparation of a freshly-formulated teaching project. The aim of this project is to provide a classroom public policy study program wherein students debate policy issues in a carefully structured and professional fashion. This structure encompasses hands-on study of actually-litigated minority set-aside/affirmative action controversies before the U.S. Supreme Court, with every student always utilizing the primary documents (the litigants\u27 briefs) used by the Supreme Court Justices themselves. These briefs provide readymade resources fueling policy debate on either side of each case

    Harnessing the Melanocortin System in the control of food intake and glucose homeostasis

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    The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.</p

    Polytypic Genetic Programming

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    Program synthesis via heuristic search often requires a great deal of boilerplate code to adapt program APIs to the search mechanism. In addition, the majority of existing approaches are not type-safe: i.e. they can fail at runtime because the search mechanisms lack the strict type information often available to the compiler. In this article, we describe Polytope, a Scala framework that uses polytypic programming, a relatively recent advance in program abstraction. Polytope requires a minimum of boilerplate code and supports a form of strong-typing in which type rules are automatically enforced by the compiler, even for search operations such as mutation which are applied at run-time. By operating directly on language-native expressions, it provides an embeddable optimization procedure for existing code. We give a tutorial example of the specific polytypic approach we adopt and compare both runtime efficiency and required lines of code against the well-known EpochX GP framework, showing comparable performance in the former and the complete elimination of boilerplate for the latter

    Intensity modulated radiotherapy for elderly bladder cancer patients

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    <p>Abstract</p> <p>Background</p> <p>To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer.</p> <p>Methods</p> <p>From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison.</p> <p>Results</p> <p>The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% <it>vs </it>.37.5%, respectively; the corresponding values for disease-free survival were 58.3% <it>vs</it>. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% <it>vs</it>. 83.3%, respectively; and for metastases-free survival, the values were 66.7% <it>vs</it>. 60.0%, respectively. The 2-year OS rates for T1, 2 <it>vs</it>. T3, 4 were 66.7% <it>vs</it>. 35.4%, respectively (<it>p </it>= 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, <it>p </it>= 0.004).</p> <p>Conclusion</p> <p>IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.</p

    Inter-Relationship between Testicular Dysgenesis and Leydig Cell Function in the Masculinization Programming Window in the Rat

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    The testicular dysgenesis syndrome (TDS) hypothesis proposes that maldevelopment of the testis, irrespective of cause, leads to malfunction of the somatic (Leydig, Sertoli) cells and consequent downstream TDS disorders. Studies in rats exposed in utero to di(n-butyl) phthalate (DBP) have strongly supported the TDS concept, but so far no direct evidence has been produced that links dysgenesis per se to somatic cell dysfunction, in particular to androgen production/action during the ‘masculinization programming window’ (MPW; e15.5–e18.5). Normal reproductive tract development and anogenital distance (AGD) are programmed within the MPW, and TDS disorders arise because of deficiencies in this programming. However, DBP-induced focal testicular dysgenesis (Leydig cell aggregation, ectopic Sertoli cells, malformed seminiferous cords) is not evident until after the MPW. Therefore, we used AGD as a read-out of androgen exposure in the MPW, and investigated if this measure was related to objectively quantified dysgenesis (Leydig cell aggregation) at e21.5 in male fetuses exposed to vehicle, DBP (500 or 750 mg/kg/day) or the synthetic glucocorticoid dexamethasone (Dex; alone or plus DBP-500) from e15.5–e18.5 (MPW), e13.5–e20.5 or e19.5–e20.5 (late window). Dysgenesis was found only in animals exposed to DBP during the MPW, and was negatively correlated (R2 = −0.5) with AGD at e21.5 and at postnatal day 8, irrespective of treatment period. Dysgenesis was also negatively correlated (R2 = –0.5) with intratesticular testosterone (ITT) at e21.5, but only when treatments in short windows (MPW, late window) were excluded; the same was true for correlation between AGD and ITT. We conclude that AGD, reflecting Leydig cell function solely within the MPW, is strongly related to focal dysgenesis. Our results point to this occurring because of a common early mechanism, targeted by DBP that determines both dysgenesis and early (during the MPW) fetal Leydig cell dysfunction. The findings provide strong validation of the TDS hypothesis

    Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

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    Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

    GRB 071003: Broadband Follow-up Observations of a Very Bright Gamma-Ray Burst in a Galactic Halo

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    The optical afterglow of long-duration GRB 071003 is among the brightest yet to be detected from any GRB, with R ~ 12 mag in KAIT observations starting 42 s after the GRB trigger, including filtered detections during prompt emission. However, our high S/N ratio afterglow spectrum displays only extremely weak absorption lines at what we argue is the host redshift of z = 1.60435 - in contrast to the three other, much stronger Mg II absorption systems observed at lower redshifts. Together with Keck adaptive optics observations which fail to reveal a host galaxy coincident with the burst position, our observations suggest a halo progenitor and offer a cautionary tale about the use of Mg II for GRB redshift determination. We present early through late-time observations spanning the electromagnetic spectrum, constrain the connection between the prompt emission and early variations in the light curve (we observe no correlation), and discuss possible origins for an unusual, marked rebrightening that occurs a few hours after the burst: likely either a late-time refreshed shock or a wide-angle secondary jet. Analysis of the late-time afterglow is most consistent with a wind environment, suggesting a massive star progenitor. Together with GRB 070125, this may indicate that a small but significant portion of star formation in the early universe occurred far outside what we consider a normal galactic disk.Comment: 24 pages, 14 figures, 12 tables. Accepted for publication by ApJ. Contains minor revisions and additional author

    Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy?

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    <p>Abstract</p> <p>Background</p> <p>The selection of an anastomosis method after a distal gastrectomy is a highly debatable topic; however, the available documentation lacks the necessary research based on a comparison of early postoperative complications. This study was conducted to investigate the difference of early postoperative complications between Billroth I and Billroth II types of anastomosis for distal gastrectomies.</p> <p>Methods</p> <p>A total of 809 patients who underwent distal gastrectomies for gastric cancer during four years were included in the study. The only study endpoint was analysis of in-patients' postoperative complications. The risk adjusted complication rate was compared by POSSUM (Physiological and operative severity score for enumeration of morbidity and mortality) and the severity of complications was compared by Rui Jin Hospital classification of complication.</p> <p>Results</p> <p>Complication rate of Billroth II type of anastomosis was almost double of that in Billroth I (P = 0.000). Similarly, the risk adjusted complication rate was also higher in Billroth II group. More severe complications were observed and the postoperative duration was significantly longer in Billroth II type (P = 0.000). Overall expenditure was significantly higher in Billroth II type (P = 0.000).</p> <p>Conclusion</p> <p>Billroth II method of anastomosis was associated with higher rate of early postoperative complications. Therefore, we conclude that the Billroth I method should be the first choice after a distal gastrectomy as long as the anatomic and oncological environment of an individual patient allows us to perform it. However more prospective studies should be designed to compare the overall surgical outcomes of both anastomosis methods.</p

    Skeletal Site-Related Variation in Human Trabecular Bone Transcriptome and Signaling

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    BACKGROUND: The skeletal site-specific influence of multiple genes on bone morphology is recognised, but the question as to how these influences may be exerted at the molecular and cellular level has not been explored. METHODOLOGY: To address this question, we have compared global gene expression profiles of human trabecular bone from two different skeletal sites that experience vastly different degrees of mechanical loading, namely biopsies from iliac crest and lumbar spinal lamina. PRINCIPAL FINDINGS: In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showed significantly increased levels of expression; 3406 transcripts were up- whilst 838 were down-regulated. Interestingly, all gene transcripts that have been recently demonstrated to be markers of osteocyte, as well as osteoblast and osteoclast-related genes, were markedly up-regulated in the spine. The transcriptome data is consistent with osteocyte numbers being almost identical at the two anatomical sites, but suggesting a relatively low osteocyte functional activity in the iliac crest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activity in the spine than iliac crest. This analysis has also led to the identification of expression of a number of transcripts, previously known and novel, which to our knowledge have never earlier been associated with bone growth and remodelling. CONCLUSIONS AND SIGNIFICANCE: This study provides molecular evidence explaining anatomical and micro-architectural site-related changes in bone cell function, which is predominantly attributable to alteration in cell transcriptional activity. A number of novel signaling molecules in critical pathways, which have been hitherto not known to be expressed in bone cells of mature vertebrates, were identified

    First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

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    The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ
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