Basic essential education program (BEEP): a brief introductory faculty development course for medical teachers

Background: Physicians have a unique role in teaching future physicians and allied health professionals. Yet, most medical doctors have limited instruction in this critical component of their daily activity. Methods: This study was a prospective cohort study of the effectiveness of a local teaching program at two teaching hospitals for junior faculty. Based on a needs analysis and literature review, the teaching program was developed in an accessible and compact format of six consecutive, one-hour "lunch and learn" sessions, held locally over a six week period. Pre-post questionnaires and focus groups were used to evaluate the program. Results: Participants reported being satisfied with the course as whole, particularly in respect to the format and location. There was an improvement in their knowledge in all content areas covered. The greatest benefits were derived from fostering a community of practice and having the opportunity to role play and simulate teaching skills. An attitudinal change towards teaching was noted. Conclusions: A brief, local faculty development program was effective in enhancing physicians’ knowledge, skills, and attitudes in teaching

α-FAPbI3 powder presynthesized by microwave irradiation for photovoltaic applications

The development of up-scalable and high-throughput methodologies to fabricate high-efficiency lead halide perovskite solar cells (PSCs) based on α-phase formamidinium lead iodide (FAPbI3) is one of the main challenges of making solar energy economical. In this context, PSCs based on α-phase formamidinium lead iodide (FAPbI3) are receiving special attention as this perovskite has the highest theoretical photoconversion efficiency (PCE). This manuscript reports an easy, fast and environmentally-friendly way to prepare α-FAPbI3 black powders by a microwave-assisted synthesis and their application in solar cells. The α-FAPbI3 powders consist of micrometric particles that can be stored for weeks in a closed vial at ambient conditions. This technique presents an enormous potential for upscaling FAPbI3 powders synthesis prerequisite necessary for large scale commercialization. The performance of the presynthesized FAPbI3-based solar cell was comparable with that of PSCs fabricated with the conventional procedure from precursors solutions, leading to a maximum PCE value of 18.15%, with an VOC=1.07 V, a Jsc=24.28 mA/cm2 and an FF=70%. The presynthesized FAPbI3-based solar cell was further modified through the addition of methylammonium chloride (MACl) in order to study the generality of the approach. The optical band gap for the presynthesized perovskite shifted from ∼1.43 eV to ∼1.55 eV with the MACl addition (30 mol%), indicating the formation of a mixed methylammonium and formamidinium based perovskite material (MAFAPbI3). In addition, the incorporation of MACl led to an increase in the grain size and the disappearance of the residual δ-phase perovskite, thus improving the efficiency of the final device.Funding for open access charge: CRUE-Universitat Jaume

A sociological exploration of the tensions related to interprofessional collaboration in acute-care discharge planning

Patient discharge is a key concern in hospitals, particularly in acute care, given the multifaceted and challenging nature of patients' healthcare needs. Policies on discharge have identified the importance of interprofessional collaboration, yet research has described its limitations in this clinical context. This study aimed to extend our understanding of interprofessional interactions related to discharge in a general internal medicine setting by using sociological theories to illuminate the existence of, and interplay between, structural factors and microlevel practices. An ethnographic approach was employed to obtain an in-depth insight into healthcare providers' perspectives, behaviours, and interactions regarding discharge. Data collection involved observations, interviews, and document analysis. Approximately 65 hours of observations were undertaken, 23 interviews were conducted with healthcare providers, and government and hospital discharge documents were collected. Data were analysed using a directed content approach. The findings indicate the existence of a medically dominated division of healthcare labour in patient discharge with opportunities for some interprofessional negotiations; the role of organizational routines in facilitating and challenging interprofessional negotiations in patient discharge; and tensions in organizational priorities that impact an interprofessional approach to discharge. The findings provide insight into the various levels at which interventions can be targeted to improve interprofessional collaboration in discharge while recognizing the organizational tensions that challenge an interprofessional approach

Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations

All authors: Olga Y. Gorlova , Yafang Li, Ivan Gorlov, Jun Ying, Wei V. Chen, Shervin Assassi, John D. Reveille, Frank C. Arnett, Xiaodong Zhou, Lara Bossini-Castillo, Elena Lopez-Isac, Marialbert Acosta-Herrera, Peter K. Gregersen, Annette T. Lee, Virginia D. Steen, Barri J. Fessler, Dinesh Khanna, Elena Schiopu, Richard M. Silver, Jerry A. Molitor, Daniel E. Furst, Suzanne Kafaja, Robert W. Simms, Robert A. Lafyatis, Patricia Carreira, Carmen Pilar Simeon, Ivan Castellvi, Emma Beltran, Norberto Ortego, Christopher I. Amos, Javier Martin, Maureen D. Mayes.Data Availability Statement: Genetic data is available from dbGaP repository (https://www.ncbi. nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_ id=phs000357.v1.p1).Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly due to the limited sample size of African Americans.Funding was provided to MDM by the National Institutes of Health (NIH) the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS https://www.niams.nih.gov/) Centers of Research Translation (CORT) P50-AR054144, NIH grant N01-AR-02251 and R01-AR-055258, and the Department of Defense (DD) Congressionally Directed Medical Research Program (http://cdmrp.army.mil/) W81XWH-07-1-011 and WX81XWH-13-1-0452 for the collection, analysis and interpretation of the data

Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts.

Inhibition of vascular endothelial growth factor increases response rates to chemotherapy and progression-free survival in glioblastoma. However, resistance invariably occurs, prompting the urgent need for identification of synergizing agents. One possible strategy is to understand tumor adaptation to microenvironmental changes induced by antiangiogenic drugs and test agents that exploit this process. We used an in vivo glioblastoma-derived xenograft model of tumor escape in presence of continuous treatment with bevacizumab. U87-MG or U118-MG cells were subcutaneously implanted into either BALB/c SCID or athymic nude mice. Bevacizumab was given by intraperitoneal injection every 3 days (2.5 mg/kg/dose) and/or dichloroacetate (DCA) was administered by oral gavage twice daily (50 mg/kg/dose) when tumor volumes reached 0.3 cm(3) and continued until tumors reached approximately 1.5-2.0 cm(3). Microarray analysis of resistant U87 tumors revealed coordinated changes at the level of metabolic genes, in particular, a widening gap between glycolysis and mitochondrial respiration. There was a highly significant difference between U87-MG-implanted athymic nude mice 1 week after drug treatment. By 2 weeks of treatment, bevacizumab and DCA together dramatically blocked tumor growth compared to either drug alone. Similar results were seen in athymic nude mice implanted with U118-MG cells. We demonstrate for the first time that reversal of the bevacizumab-induced shift in metabolism using DCA is detrimental to neoplastic growth in vivo. As DCA is viewed as a promising agent targeting tumor metabolism, our data establish the timely proof of concept that combining it with antiangiogenic therapy represents a potent antineoplastic strategy

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)