36 research outputs found

    Closing the Communication Gap Between Undergraduates and Mathematics Professors

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    This research sought to determine the sources of communicative difficulties that exist between undergraduate students and international faculty (the communication gap) specifically within the field of mathematics. The hypotheses were as follows: 1) The communication gap results from students\u27 perceptual difficulties in understanding their professors and their own biases against international faculty. 2) The communication gap can be addressed by administering to students a training program that not only provides instruction on accent features, but also attempts to confront accent bias and persuades the student to adopt a more accommodating view of their professors\u27 accents. Fifteen experimental sessions were conducted in October 2009, in order to collect both quantitative data and qualitative data on the communication gap and students\u27 views thereof. Quantitative data was collected through testing sessions that assessed students\u27 baseline performance on mathematics assessments and their performance on one of three assessments after completing either the linguistic training program, a program meant to simulate bias creation, or a control program. Eighty-one undergraduates at the College of William and Mary in Williamsburg, VA, took part in one of six testing sessions. Each assessment was tied to a video lesson taught by a professor from India, and the training program was specifically engineered to address the features of this professor\u27s accent. The variable of interest was each student\u27s improvement in scores between the baseline and post-training assessments, as following from Hypothesis 2, I hypothesized that the students who participated in linguistic training program would produce greater improvement scores than the control group. I also hypothesized, on the basis of Hypothesis 1, that students who participated in the bias program would produce significantly worse improvement scores than the control group. An analysis of the data resulting from the testing sessions revealed no significant difference in improvement scores arising from membership in one of these three testing groups. Qualitative data was collected through discussion sessions with testing session participants two weeks after the testing sessions and through questionnaires administered at the end of the testing sessions. Fifty-seven undergraduates from the original sample of 81 participated in discussion sessions. The discussion sessions addressed issues surrounding the communication gap, including classes with international professors, frustrations with communication breakdown, and suggestions for solutions to the communication gap. Data from these sessions were analyzed using an ethnographic approach, revealing substantial cross-group trends and themes. While students did not universally embrace the idea that they contributed to the communication gap and so bore responsibility for closing it, almost all agreed that further research on the issue was vital. A quantitative analysis of response data on the post-testing questionnaire revealed a significant effect of linguistic training on linguistic attitudes. Therefore, although it was not reflected in assessment scores, the use of linguistic training did have a positive effect on students. Further research in this area is vital to determine a reliable application of this result to greater professor-student communication

    Distinct Airway Inflammatory Pathways Associated with Asthma Exacerbations are Modulated by Mepolizumab Therapy in Children

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    Rationale: Identification of specific airway inflammatory pathways can lead to effective personalized treatment with biologics in asthma and insights to mechanisms of action. Methods: 290 urban children with exacerbation-prone asthma and ≥150/mm3 blood eosinophils were randomized (1:1) to placebo or mepolizumab added to guideline-based care. Nasal lavage samples were collected at randomization and during treatment for RNA-sequencing, and analyzed by cell-deconvolution modular analysis to assess genome-wide expression patterns associated with exacerbation number and effect of treatment. Results: Mepolizumab significantly reduced the frequency of exacerbations compared to placebo. At randomization, there were no differences in expression between treatment groups; multiple modules were subsequently differentially expressed during mepolizumab but not placebo treatment. Furthermore, expression levels of multiple modules were associated with the exacerbation number during the study, with distinct relationships observed in the placebo and/or mepolizumab groups. Notably, higher expression at randomization of an eosinophil-associated module enriched for Type-2 genes including IL4, IL5, and IL13, was associated with increased exacerbations in placebo (β=0.19, p\u3c0.001), but not mepolizumab-treated children (interaction p\u3c0.01). Furthermore, mepolizumab treatment reduced expression of this module (Fold-change=0.62, p\u3c0.001). In contrast, higher expression at randomization of an eosinophil-associated module enriched for eosinophil activation (e.g. CD9) and mucus hypersecretion (e.g. MUC5AC) genes was associated with exacerbation number in both groups throughout the study (β=0.18, p\u3c0.01) and was unaltered by mepolizumab therapy. Conclusions: Multiple distinct airway inflammation patterns were identified associated with exacerbation frequency. These findings identify inflammatory endotypes and indicate likelihood and potential mechanisms of a beneficial clinical response to mepolizumab therapy to prevent exacerbations

    The North American tree-ring fire-scar network

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    Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America

    Recent Progress in Solar Atmospheric Neutrino Searches with IceCube

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    Cosmic-rays interacting with nucleons in the solar atmosphere produce a cascade of particles that give rise to a flux of high-energy neutrinos and gamma-rays. Fermi has observed this gamma-ray flux; however, the associated neutrino flux has escaped observation. In this contribution, we put forward two strategies to detect these neutrinos, which, if seen, would push forward our understanding of the solar atmosphere and provide a new testing ground of neutrino properties. First, we will extend the previous analysis, which used high-energy through-going muon events collected in the years of maximum solar activity and yielded only flux upper limits, to include data taken during the solar minima from 2018 to 2020. Extending the analysis to the solar minima is important as the gamma-ray data collected during past solar cycles indicates a possible enhancement in the high-energy neutrino flux. Second, we will incorporate sub-TeV events and include contributions from all neutrino flavors. These will improve our analysis sensitivity since the solar atmospheric spectrum is soft and, due to oscillation, contains significant contributions of all neutrino flavors. As we will present in this contribution, these complementary strategies yield a significant improvement in sensitivity, making substantial progress towards observing this flux

    Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

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    The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

    System identification of metabotropic glutamate receptor dependent long–term depression

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    Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR) dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked and it is believed that several crucial mechanisms still remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to the author’s knowledge it is the first time that SI methods are applied on electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse engineering of mGluR-LTD responses. It is suggested that such SI methods can aid to unravel the complexities of synaptic function

    Phenotype-directed Therapy with Mepolizumab for Urban Children with Exacerbation-Prone Asthma

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    Rationale: Asthma exacerbations are common in urban children and have significant short- and long-term consequences. Elevated peripheral blood and airway eosinophils have been identified as risk factors for exacerbations, and therapies targeting these biomarkers reduce exacerbations in adults; however, data on anti-eosinophil treatment in children and adolescents are limited. The primary objective of this study is to determine if phenotype-directed use of mepolizumab reduces the rate of asthma exacerbations in urban children. Methods: Urban children 6-17 years of age (n=290) with exacerbation-prone asthma (2+ exacerbations in previous year) and blood eosinophils ≥150/mm3 were randomized 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo every 4 weeks added to guideline-based care for 1 year. The primary outcome was the number of asthma exacerbations treated with systemic corticosteroids; a comparison of the two treatment groups was evaluated using a negative-binomial model. Results: Mepolizumab significantly reduced peripheral blood eosinophils (p\u3c0.01) and nasal eosinophils (p\u3c0.01). The rate of asthma exacerbations was significantly lower in mepolizumab (0.96 exacerbations/year) vs. placebo (1.30 exacerbations/year) treated participants [relative risk 0.73 (95% confidence interval 0.56-0.96), p=0.027]. There were no significant differences in secondary outcomes, including time to first exacerbation, lung function, quality of life, or composite asthma severity index (CASI). Post hoc, the time to second asthma exacerbation increased significantly with mepolizumab (p=0.02). Adverse events were similar between groups. Conclusions: Phenotype-directed therapy with mepolizumab in urban children and adolescents with exacerbation-prone eosinophilic asthma significantly reduced recurrent exacerbations and was well tolerated, but did not impact other asthma outcomes

    PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors.

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    INTRODUCTION: Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses. AIM: To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3. METHODS: Subjects were administered 200 µg/kg (major procedures) or 75 µg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75 µg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period. RESULTS: Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI: 47.8%-100%) for minor procedures and 66.7% (95% CI: 22.3%-95.7%) for major procedures; 81.8% (95% CI: 48.2%-97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported. CONCLUSION: Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI
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