Creating Online Lessons: A Faculty Development Seminar Series

The World Wide Web is being used increasingly to deliver instruction in medical education. Consequently, there is a need to train faculty in developing and implementing online instruction. We developed and implemented a seminar series to teach faculty to create educationally sound, well designed online instruction. Instruction was delivered to 15 participants via a six session seminar on developing web based lessons, supplemented with web-based instruction. First, the participants learned the basics of instructional design via a web based module. They then completed content outlines for their online lessons prior to the first seminar. Lesson development, web site development and the use of a web based instructional shell to implement the online lessons were each taught in two two hour sessions. Eight participants developed online lessons and four actually implemented them. Feedback was mostly positive, with suggestions for improvement. All eight participants who completed the series said they would recommend it to their colleagues. Because a longitudinal workshop type of seminar series requires a large amount of participant time outside of class, a six month seminar series may be too long. It is important at the beginning of the series to help participants select topics suitable for online instruction and to help them narrow their topics. We may change the attendance guidelines so faculty would attend only the session on instructional design and have their staff attend the technical sessions on web site design, HTML editing and online course delivery systems. This would better match the actual practice of faculty designing the instruction and staff developing it

Climatic change controls productivity variation in global grasslands.

Detection and identification of the impacts of climate change on ecosystems have been core issues in climate change research in recent years. In this study, we compared average annual values of the normalized difference vegetation index (NDVI) with theoretical net primary productivity (NPP) values based on temperature and precipitation to determine the effect of historic climate change on global grassland productivity from 1982 to 2011. Comparison of trends in actual productivity (NDVI) with climate-induced potential productivity showed that the trends in average productivity in nearly 40% of global grassland areas have been significantly affected by climate change. The contribution of climate change to variability in grassland productivity was 15.2-71.2% during 1982-2011. Climate change contributed significantly to long-term trends in grassland productivity mainly in North America, central Eurasia, central Africa, and Oceania; these regions will be more sensitive to future climate change impacts. The impacts of climate change on variability in grassland productivity were greater in the Western Hemisphere than the Eastern Hemisphere. Confirmation of the observed trends requires long-term controlled experiments and multi-model ensembles to reduce uncertainties and explain mechanisms

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression1. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR–Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells.M.L.B. is supported by a Cancer Research UK Clinician Scientist Fellowship (C53779/A20097), Addenbrooke’s Charitable Trust award and NIHR fellowship. P.J.L. is supported by a Wellcome Trust PRF (101835/Z/13/Z) and work in the Lehner laboratory is supported by NHSBT, NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke’s Charitable Trust M.A.D. is supported by a Senior Leukaemia Foundation Australia Fellowship and work in the Dawson laboratory is supported by the NHMRC (Grants 1085015, 1106444 and 1106447) Cancer Council Victoria and Leukaemia Foundation Australia. Cancer Research UK (C53779/A20097

Rural Opioid Prevention and Treatment Strategies: The Experience in Four States [Working Paper]

Although opioid use rates are comparable in rural and urban counties, rural opioid users tend to be younger, unmarried, have lower incomes, and are more likely to lack health insurance, all vulnerabilities that may negatively impact their ability to seek treatment and recover. Additionally, the rural health care system is characterized by numerous resource, workforce, access, and geographic challenges that complicate the delivery of specialized care for OUDs in rural communities. The nature and scope of the opioid crisis vary across rural communities and require multifaceted, community-based strategies to address the problem. Based on interviews with key stakeholders in Indiana, North Carolina, Vermont, and Washington State, this qualitative study explores promising state and community strategies to tackle the opioid crisis in rural communities and identifies rural challenges to the provision of OUD prevention, treatment, and recovery services

Torus fibrations and localization of index II

We give a framework of localization for the index of a Dirac-type operator on an open manifold. Suppose the open manifold has a compact subset whose complement is covered by a family of finitely many open subsets, each of which has a structure of the total space of a torus bundle. Under an acyclic condition we define the index of the Dirac-type operator by using the Witten-type deformation, and show that the index has several properties, such as excision property and a product formula. In particular, we show that the index is localized on the compact set.Comment: 47 pages, 2 figures. To appear in Communications in Mathematical Physic

Usability and Psychosocial Impact of Decision Support to Increase Sexual Health Education in American Indian and Alaska Native Communities

Despite sexual and reproductive health disparities, few evidence-based sexual health education programs exist for American Indian/Alaska Native (AI/AN) youth, with even fewer tools available to assist AI/AN communities in adopting, implementing, and maintaining such programs. iCHAMPSS (Choosing And Maintaining effective Programs for Sex education in Schools) is a theory- and web-based decision-support-system designed to address dissemination barriers and increase the reach and fidelity of evidence-based programs (EBPs), specifically sexual health education programs. To investigate the potential of iCHAMPSS in AI/AN communities, we pilot-tested iCHAMPSS with adult stakeholders (N = 36) from agencies across the country that serve AI/AN communities. Stakeholders were recruited to review selected iCHAMPSS tools over two weeks in spring 2016. Pre- and post-surveys were administered to assess usability constructs, short-term psychosocial outcomes, and perceived feasibility. Data were analyzed using descriptive and non-parametric statistics. iCHAMPSS was perceived as acceptable, easy to use, credible, appealing, more helpful than current resources, and impactful of EBP adoption, implementation, and maintenance. Conversely, using iCHAMPSS significantly increased participants’ perceived barriers to adopting an EBP (p = 0.01). Overall, AI/AN stakeholders responded positively to iCHAMPSS, indicating the potential for adaptation to support the dissemination and implementation of evidence-based sexual health education in AI/AN communities

A protocol for developing, disseminating, and implementing a core outcome set for stress urinary incontinence.

INTRODUCTION: Randomized trials evaluating interventions for stress urinary incontinence (SUI) have been using variable outcome measures, reporting a variety of outcomes. Alongside this variation across studies, outcome-reporting flaws contribute to a limited use of research to inform clinical practice. The development and use of core outcome sets (COSs) in future trials would ensure that outcomes important to different stakeholders and primarily women with SUI are reported more consistently and comprehensively. METHODS: An international steering group including healthcare professionals, researchers, and women with urinary incontinence will guide the development of this COS. Potential outcomes will be identified through comprehensive literature reviews. These outcomes will be entered into an international, multiperspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and women with urinary incontinence, will be invited to participate. The modified Delphi method encourages stakeholder group convergence toward collective agreement, also referred as consensus, core outcomes. DISCUSSION: Dissemination and implementation of the resulting COS within an international context will be promoted and reviewed. Embedding the COS for SUI within future clinical trials, systematic reviews and clinical practice guidelines could make a significant contribution to advancing the value of research in informing clinical practice, enhancing patient care and improving outcomes. The infrastructure created by developing a COS for SUI could be leveraged in other settings, for example, selecting research priorities and clinical practice guideline development

Substitutions in the redox-sensing PAS domain of the NifL regulatory protein define an inter-subunit pathway for redox signal transmission

The Per-ARNT-Sim (PAS) domain is a conserved a/ß fold present within a plethora of signalling proteins from all kingdoms of life. PAS domains are often dimeric and act as versatile sensory and interaction modules to propagate environmental signals to effector domains. The NifL regulatory protein from Azotobacter vinelandii senses the oxygen status of the cell via an FAD cofactor accommodated within the first of two amino-terminal tandem PAS domains, termed PAS1 and PAS2. The redox signal perceived at PAS1 is relayed to PAS2 resulting in conformational reorganization of NifL and consequent inhibition of NifA activity. We have identified mutations in the cofactor-binding cavity of PAS1 that prevent 'release' of the inhibitory signal upon oxidation of FAD. Substitutions of conserved ß-sheet residues on the distal surface of the FAD-binding cavity trap PAS1 in the inhibitory signalling state, irrespective of the redox state of the FAD group. In contrast, substitutions within the flanking A'a-helix that comprises part of the dimerization interface of PAS1 prevent transmission of the inhibitory signal. Taken together, these results suggest an inter-subunit pathway for redox signal transmission from PAS1 that propagates from core to the surface in a conformation-dependent manner requiring a flexible dimer interface

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool.

To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT)

Native IYG: Improving Psychosocial Protective Factors for HIV/STI and Teen Pregnancy Prevention among Youth in American Indian/Alaska Native Communities

Background: Few HIV/STI and pregnancy prevention programs for youth in American Indian and Alaska Native (AI/AN) communities have been rigorously evaluated despite sexual health disparities in this population. This study reports the evaluation of a culturally adapted Internet-based HIV/STI and pregnancy prevention program for AI/AN youth, Native It’s Your Game (Native IYG). Methods: A randomized study was conducted with 523 youth (12 to 14 years old), recruited from 25 tribal sites in Alaska, Arizona, and the Pacific Northwest. Participants were surveyed at baseline and upon completion of treatment or comparison interventions. Multivariable linear regression models were used to assess impact on short term psychosocial determinants of sexual initiation. Results: A sample of 402 intervention (n=290) and comparison (n=112) youth completed the post-intervention survey (76.9% retention) from 1 to 462 days post-baseline (mean = 114, SD = ±96.67). Participants were 55.5% female, mean age of 13.0 (± 0.97) years with 86.1% self-reporting as AI/AN. Reasons not to have sex, STI knowledge, condom knowledge, condom availability self-efficacy, and condom use self-efficacy were significantly impacted (all P ≤ .01). Limitations included variability in intervention exposure and time between data collection time points. Conclusions: Native IYG demonstrated efficacy to impact short-term psychosocial determinants of sexual behavior in a sample of predominantly AI/AN middle school youth