230 research outputs found
Beyond the Economic Turmoil of the Asian Financial Crisis: Indonesia\u27s Struggle to Cope with Insolvency
Collaborative Power: Graduate Students Creating and Implementing Faculty Development Workshops on Multilingual Writing Pedagogy
The increasing numbers multilingual students in US universities, whether international students or multilingual citizens and permanent residents, have made it clear that students’ language needs can no longer be relegated to the ‘experts’ in specialized courses or tutoring centers. All faculty will teach multilingual students, yet few faculty have received specialized training to prepare them to work effectively with the multilingual writers in their classrooms. While there is a need for professional development efforts designed to help faculty more effectively teach multilingual writing, institutional divisions between first language (L1) and second language (L2) writing instruction pose challenges for the organization and delivery of such professional development efforts. One way to overcome such challenges is through grassroots forms of collaboration across institutional boundaries. This article reports on one such grassroots effort, the creation of two faculty development workshops designed to help teachers across the disciplines to work more effectively with multilingual writers. These workshops were unique in that they were initiated by an interdisciplinary graduate student led research group. This article describes the formation of this group, the creation and curriculum of the workshops, and ongoing adaptation of the workshops for new audiences. We also consider faculty responses to the workshops and reflect on the challenges and rewards of such grassroots collaborative efforts
Benzo-fused Lactams from a Diversity-oriented Synthesis (DOS) Library as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake
We report a new series of 8-membered benzo-fused lactams that inhibit cellular lipid uptake from HDL particles mediated by Scavenger Receptor, Class B, Type I (SR-BI). The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR), measuring the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is part of a previously reported diversity-oriented synthesis (DOS) library prepared via a build-couple-pair approach. Detailed structure–activity relationship (SAR) studies were performed with a selection of the original library, as well as additional analogs prepared via solution phase synthesis. These studies demonstrate that the orientation of the substituents on the aliphatic ring have a critical effect on activity. Additionally, a lipophilic group is required at the western end of the molecule, and a northern hydroxyl group and a southern sulfonamide substituent also proved to be optimal. Compound 2p was found to possess a superior combination of potency (av IC50 = 0.10 μM) and solubility (79 μM in PBS), and it was designated as probe ML312
Discovery of Bisamide-heterocycles as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake
A new series of potent inhibitors of cellular lipid uptake from HDL particles mediated by scavenger receptor, class B, type I (SR-BI) was identified. The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is characterized by a linear peptidomimetic scaffold with two adjacent amide groups, as well as an aryl-substituted heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component reaction, and select enantiopure compounds were prepared via a stepwise sequence. Structure–activity relationship (SAR) studies suggest an oxygenated arene is preferred at the western end of the molecule, as well as highly lipophilic substituents on the central and eastern nitrogens. Compound 5e, with (R)-stereochemistry at the central carbon, was designated as probe ML279. Mechanistic studies indicate that ML279 stabilizes the interaction of HDL particles with SR-BI, and its effect is reversible. It shows good potency (IC50 = 17 nM), is non-toxic, plasma stable, and has improved solubility over our alternative probe ML278
Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport
A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC50 = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action
Circulation first – the time has come to question the sequencing of care in the ABCs of trauma; an American Association for the Surgery of Trauma multicenter trial
Background The traditional sequence of trauma care: Airway, Breathing, Circulation (ABC) has been practiced for many years. It became the standard of care despite the lack of scientific evidence. We hypothesized that patients in hypovolemic shock would have comparable outcomes with initiation of bleeding treatment (transfusion) prior to intubation (CAB), compared to those patients treated with the traditional ABC sequence. Methods This study was sponsored by the American Association for the Surgery of Trauma multicenter trials committee. We performed a retrospective analysis of all patients that presented to trauma centers with presumptive hypovolemic shock indicated by pre-hospital or emergency department hypotension and need for intubation from January 1, 2014 to July 1, 2016. Data collected included demographics, timing of intubation, vital signs before and after intubation, timing of the blood transfusion initiation related to intubation, and outcomes. Results From 440 patients that met inclusion criteria, 245 (55.7%) received intravenous blood product resuscitation first (CAB), and 195 (44.3%) were intubated before any resuscitation was started (ABC). There was no difference in ISS, mechanism, or comorbidities. Those intubated prior to receiving transfusion had a lower GCS than those with transfusion initiation prior to intubation (ABC: 4, CAB:9, p = 0.005). Although mortality was high in both groups, there was no statistically significant difference (CAB 47% and ABC 50%). In multivariate analysis, initial SBP and initial GCS were the only independent predictors of death. Conclusion The current study highlights that many trauma centers are already initiating circulation first prior to intubation when treating hypovolemic shock (CAB), even in patients with a low GCS. This practice was not associated with an increased mortality. Further prospective investigation is warranted. Trial registration IRB approval number: HM20006627. Retrospective trial not registered
Randomised Trial to Evaluate the Effectiveness and Impact of Offering Postvisit Decision Support and Assistance in Obtaining Physician-Recommended Colorectal Cancer Screening: The e-Assist: Colon Health Study - A Protocol Study
INTRODUCTION: How to provide practice-integrated decision support to patients remains a challenge. We are testing the effectiveness of a practice-integrated programme targeting patients with a physician recommendation for colorectal cancer (CRC) screening.
METHODS AND ANALYSIS: In partnership with healthcare teams, we developed \u27e-assist: Colon Health\u27, a patient-targeted, postvisit CRC screening decision support programme. The programme is housed within an electronic health record (EHR)-embedded patient portal. It leverages a physician screening recommendation as the cue to action and uses the portal to enrol and intervene with patients. Programme content complements patient-physician discussions by encouraging screening, addressing common questions and assisting with barrier removal. For evaluation, we are using a randomised trial in which patients are randomised to receive e-assist: Colon Health or one of two controls (usual care plus or usual care). Trial participants are average-risk, aged 50-75 years, due for CRC screening and received a physician order for stool testing or colonoscopy. Effectiveness will be evaluated by comparing screening use, as documented in the EHR, between trial enrollees in the e-assist: Colon Health and usual care plus (CRC screening information receipt) groups. Secondary outcomes include patient-perceived benefits of, barriers to and support for CRC screening and patient-reported CRC screening intent. The usual care group will be used to estimate screening use without intervention and programme impact at the population level. Differences in outcomes by study arm will be estimated with hierarchical logit models where patients are nested within physicians.
ETHICS AND DISSEMINATION: All trial aspects have been approved by the Institutional Review Board of the health system in which the trial is being conducted. We will disseminate findings in diverse scientific venues and will target clinical and quality improvement audiences via other venues. The intervention could serve as a model for filling the gap between physician recommendations and patient action.
TRIAL REGISTRATION NUMBER: NCT02798224; Pre-results
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