657 research outputs found

    If You Build It, They Will Come: What Students Say About Experiential Learning

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    Our purpose here is to explore one of the “natural experiments” cited by the Task Force: the Experiential Advantage (EA) program at the University of Denver’s Sturm College of Law (Denver Law). EA was developed as a part of a greater general focus on experiential learning and is built upon the three “Carnegie Apprenticeships” – “the intellectual or cognitive,” “the forms of expert practice,” and “identity and purpose.” It was implemented at Denver Law starting with students entering in August 2013. To explore this natural experiment, we took a particular route and did so for what we see as good reason. It is often the case with such curricular experiments that the views of students are missing. But of course, it makes little sense to neglect them because such changes are supposedly made for the students’ benefit. So, it seems more than appropriate to ask them – from their perspective – if a change worked, or improved matters, as it was designed to do. This article is a first report on the findings of an extensive case study — a three-year, survey-based, study of Denver Law students concerning the EA Program “natural experiment.” The findings should be of considerable interest to the legal community, given that there is general support for experiential learning across most law schools, but a study of this kind — one exploring student views on curricular innovation — has never been conducted before. This Article is divided into four sections. The first provides a general context for Denver Law’s efforts. The second outlines the study itself, and is followed by section three, which analyzes the reasons first-year students chose Denver Law and their interest in EA and experiential learning. The fourth section changes focus and turns to Denver Law students nearing the end of their legal education – 3 and 4Ls. These students, nearing the end of their legal education, were asked a series of “look back” questions asking them about their law school experience, including the EA program and experiential learning

    Exploring Mechanisms for Model‐Dependency of the Stratospheric Response to Arctic Warming

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    The Arctic is estimated to have warmed up to four times faster than the rest of the globe since the 1980s. There is significant interest in understanding the mechanisms by which such warming may impact weather and climate at lower latitudes. One such mechanism is the “stratospheric pathway”; Arctic warming is proposed to induce a wave‐driven weakening of the stratospheric polar vortex, which may subsequently impact large‐scale tropospheric circulation. However, recent comprehensive model studies have found systematic differences in both the magnitude and sign of the stratospheric response to Arctic warming. Using a series of idealized model simulations, we show that this response is sensitive to characteristics of the warming and mean polar vortex strength. In all simulations, imposed polar warming amplifies upward wave propagation from the troposphere, consistent with comprehensive models. However, as polar warming strength and depth increases, the region through which waves can propagate is narrowed, inducing wave breaking and deceleration of the flow in the lower stratosphere. Thus, the mid‐stratosphere is less affected, with reduced sudden stratospheric warming frequency for stronger and deeper warming compared to weaker and shallower warming. We also find that the sign of the stratospheric response depends on the mean strength of the vortex, and that the stratospheric response in turn plays a role in the magnitude of the tropospheric jet response. Our results help explain the spread across multimodel ensembles of comprehensive climate models

    Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication:Results of a discrete choice experiment

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    Background: Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods: A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results: A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions: Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase

    Nitrosylation of Nitric-Oxide-Sensing Regulatory Proteins Containing [4Fe-4S] Clusters Gives Rise to Multiple Iron-Nitrosyl Complexes

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    The reaction of protein-bound iron–sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe2(NO)4(Cys)2]) and Roussin's Black Salt (RBS, [Fe4(NO)7S3]. In the latter case, the absence of 32S/34S shifts in the Fe−S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates

    The Bristol CMIP6 Data Hackathon

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    The Bristol CMIP6 Data Hackathon formed part of the Met Office Climate Data Challenge Hackathon series during 2021, bringing together around 100 UK early career researchers from a wide range of environmental disciplines. The purpose was to interrogate the under-utilised but currently most advanced climate model inter-comparison project datasets to develop new research ideas, create new networks and outreach opportunities in the lead up to COP26. Experts in different science fields, supported by a core team of scientists and data specialists at Bristol, had the unique opportunity to explore together interdisciplinary environmental topics summarised in this article

    Dietary calcium and vitamin D intakes in childhood and throughout adulthood and mammographic density in a British birth cohort

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    We examined the role of dietary calcium and vitamin D intakes in childhood and throughout adulthood in relation to mammographic density using data from a nationally representative cohort of 1161 women followed up since their birth in 1946. Dietary intakes at the age of 4 years were determined by 24-h recalls and at the ages of 36, 43 and 53 years by 5-day food records. After adjusting for known risk factors and confounders, no evidence of a relationship between dietary calcium or vitamin D intakes and mammographic density approximately at the age of 50 years was found, except for a cross-sectional relationship between dietary calcium intake at the age of 53 years and breast density in women who were post-menopausal at the time of mammography, with those in the top fifth of the distribution of calcium intake having a 0.53 s.d. lower percent breast density than those in the lowest fifth (P-value <0.01 for linear trend)

    Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus

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    BACKGROUND: Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. OBJECTIVE: To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. METHODS: 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. RESULTS: The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10(-7)) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10(-8)). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole. CONCLUSION: The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE

    A novel design process for selection of attributes for inclusion in discrete choice experiments: case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

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    A discrete choice experiment (DCE) is a method used to elicit participants’ preferences and the relative importance of different attributes and levels within a decision-making process. DCEs have become popular in healthcare; however, approaches to identify the attributes/levels influencing a decision of interest and to selection methods for their inclusion in a DCE are under-reported. Our objectives were: to explore the development process used to select/present attributes/levels from the identified range that may be influential; to describe a systematic and rigorous development process for design of a DCE in the context of thrombolytic therapy for acute stroke; and, to discuss the advantages of our five-stage approach to enhance current guidance for developing DCEs. A five-stage DCE development process was undertaken. Methods employed included literature review, qualitative analysis of interview and ethnographic data, expert panel discussions, a quantitative structured prioritisation (ranking) exercise and pilot testing of the DCE using a ‘think aloud’ approach. The five-stage process reported helped to reduce the list of 22 initial patient-related factors to a final set of nine variable factors and six fixed factors for inclusion in a testable DCE using a vignette model of presentation. In order for the data and conclusions generated by DCEs to be deemed valid, it is crucial that the methods of design and development are documented and reported. This paper has detailed a rigorous and systematic approach to DCE development which may be useful to researchers seeking to establish methods for reducing and prioritising attributes for inclusion in future DCEs.Financial support for this study was provided entirely by a grant from the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (project number: 12/5001/45)

    The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

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    &lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.&lt;/p&gt
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