Factors That Influence Medical Student Selection of an Emergency Medicine Residency Program: Implications for Training Programs

Objectives:  An understanding of student decision‐making when selecting an emergency medicine (EM) training program is essential for program directors as they enter interview season. To build upon preexisting knowledge, a survey was created to identify and prioritize the factors influencing candidate decision‐making of U.S. medical graduates. Methods:  This was a cross‐sectional, multi‐institutional study that anonymously surveyed U.S. allopathic applicants to EM training programs. It took place in the 3‐week period between the 2011 National Residency Matching Program (NRMP) rank list submission deadline and the announcement of match results. Results:  Of 1,525 invitations to participate, 870 candidates (57%) completed the survey. Overall, 96% of respondents stated that both geographic location and individual program characteristics were important to decision‐making, with approximately equal numbers favoring location when compared to those who favored program characteristics. The most important factors in this regard were preference for a particular geographic location (74.9%, 95% confidence interval [CI] = 72% to 78%) and to be close to spouse, significant other, or family (59.7%, 95% CI = 56% to 63%). Factors pertaining to geographic location tend to be out of the control of the program leadership. The most important program factors include the interview experience (48.9%, 95% CI = 46% to 52%), personal experience with the residents (48.5%, 95% CI = 45% to 52%), and academic reputation (44.9%, 95% CI = 42% to 48%). Unlike location, individual program factors are often either directly or somewhat under the control of the program leadership. Several other factors were ranked as the most important factor a disproportionate number of times, including a rotation in that emergency department (ED), orientation (academic vs. community), and duration of training (3‐year vs. 4‐year programs). For a subset of applicants, these factors had particular importance in overall decision‐making. Conclusions:  The vast majority of applicants to EM residency programs employed a balance of geographic location factors with individual program factors in selecting a residency program. Specific program characteristics represent the greatest opportunity to maximize the success of the immediate interview experience/season, while others provide potential for strategic planning over time. A working knowledge of these results empowers program directors to make informed decisions while providing an appreciation for the limitations in attracting applicants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/1/ACEM_1323_sm_DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91198/2/j.1553-2712.2012.01323.x.pd

Herd immunity drives the epidemic fadeout of avian cholera in Arctic-nesting seabirds

Avian cholera, caused by the bacterium Pasteurella multocida, is a common and important infectious disease of wild birds in North America. Between 2005 and 2012, avian cholera caused annual mortality of widely varying magnitudes in Northern common eiders (Somateria mollissima borealis) breeding at the largest colony in the Canadian Arctic, Mitivik Island, Nunavut. Although herd immunity, in which a large proportion of the population acquires immunity to the disease, has been suggested to play a role in epidemic fadeout, immunological studies exploring this hypothesis have been missing. We investigated the role of three potential drivers of fadeout of avian cholera in eiders, including immunity, prevalence of infection, and colony size. Each potential driver was examined in relation to the annual real-time reproductive number (Rt) of P. multocida, previously calculated for eiders at Mitivik Island. Each year, colony size was estimated and eiders were closely monitored, and evaluated for infection and serological status. We demonstrate that acquired immunity approximated using antibody titers to P. multocida in both sexes was likely a key driver for the epidemic fadeout. This study exemplifies the importance of herd immunity in influencing the dynamics and fadeout of epidemics in a wildlife population

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis:Design and rationale

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.Trial registration: ClinicalTrials.gov Identifier: NCT05946044.</p

Huckleberry Gold: A Specialty Market Potato Cultivar with Purple-Skin, Yellow-Flesh, High Tuber Antioxidants, and Resistance to Potato Cyst Nematode (H1) and Potato virus X (Nb and Rx1)

Huckleberry Gold is a purple-skin, yellow-flesh fresh market cultivar with similar culinary qualities to the market standard Yukon Gold. It has lower specific gravity, sucrose and vitamin C content, but a significantly higher level of tuber antioxidants than Yukon Gold. Notable disease resistant characteristics are Potato virus X resistance based on the presence of molecular markers for the PVX resistance genes, Nb and Rx1. In addition it also has the H1 gene present which confers resistance to the potato cyst nematode, Globodera rostochiensis, which has been confirmed by bioassay to pathotype Ro1. The size profile of Huckleberry Gold is smaller than Yukon Gold, allowing a better fit into specialty markets that are geared to smaller size for fresh use. Huckleberry Gold represents the first purple-skin, yellow-flesh cultivar to come from the Northwest (Tri-State) Potato Variety Development program.This is the publisher’s final pdf. The article is copyrighted by the Potato Association of America and published by Springer. It can be found at: http://link.springer.com/journal/12230Keywords: Solanum tuberosum, Variety, Globodera rostochiensis, PV

Amplification of HER2 is a marker for global genomic instability

<p>Abstract</p> <p>Background</p> <p>Genomic alterations of the proto-oncogene c-erbB-2 (HER-2/neu) are associated with aggressive behavior and poor prognosis in patients with breast cancer. The variable clinical outcomes seen in patients with similar HER2 status, given similar treatments, suggests that the effects of amplification of HER2 can be influenced by other genetic changes. To assess the broader genomic implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER2 status in patients with invasive breast cancer.</p> <p>Methods</p> <p>HER2 status was determined using the PathVysion^®assay. DNA was extracted after laser microdissection from the 181 paraffin-embedded HER2 amplified (n = 39) or HER2 negative (n = 142) tumor specimens with sufficient tumor available to perform molecular analysis. Allelic imbalance (AI) was assessed using a panel of microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer. Student t-tests and partial correlations were used to investigate relationships between genomic instability and HER2 status.</p> <p>Results</p> <p>The frequency of AI was significantly higher (<it>P </it>< 0.005) in HER2 amplified (27%) compared to HER2 negative tumors (19%). Samples with HER2 amplification showed significantly higher levels of AI (<it>P </it>< 0.05) at chromosomes 11q23, 16q22-q24 and 18q21. Partial correlations including ER status and tumor grade supported associations between HER2 status and alterations at 11q13.1, 16q22-q24 and 18q21.</p> <p>Conclusion</p> <p>The poor prognosis associated with HER2 amplification may be attributed to global genomic instability as cells with high frequencies of chromosomal alterations have been associated with increased cellular proliferation and aggressive behavior. In addition, high levels of DNA damage may render tumor cells refractory to treatment. In addition, specific alterations at chromosomes 11q13, 16q22-q24, and 18q21, all of which have been associated with aggressive tumor behavior, may serve as genetic modifiers to HER2 amplification. These data not only improve our understanding of HER in breast pathogenesis but may allow more accurate risk profiles and better treatment options to be developed.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study

Abstract Background Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored. Methods As part of the ‘Population Architecture using Genomics and Epidemiology (PAGE)’ Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses. Results We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, pinteraction = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5x10-5), vs. former/never smokers (β = 0.006, p = 0.05, pinteraction = 0.08). Conclusions These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results. Clinical Trial Registration NCT0000061

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice