EQIP\u27s First Year: A Step Closer to Higher Quality in Surgical Education.

OBJECTIVE: To describe the first year of the Educational Quality Improvement Program (EQIP) DESIGN: The Educational Quality Improvement Program (EQIP) was formed by the Association of Program Directors in Surgery (APDS) in 2018 as a continuous educational quality improvement program. Over 18 months, thirteen discrete goals for the establishment of EQIP were refined and executed through a collaborative effort involving leaders in surgical education. Alpha and beta pilots were conducted to refine the data queries and collection processes. A highly-secure, doubly-deidentified database was created for the ingestion of resident and program data. SETTING & PARTICIPANTS: 36 surgical training programs with 1264 trainees and 1500 faculty members were included in the dataset. 51,516 ERAS applications to programs were also included. Uni- and multi-variable analysis was then conducted. RESULTS: EQIP was successfully deployed within the timeline described in 2020. Data from the ACGME, ABS, and ERAS were merged with manually entered data by programs and successfully ingested into the EQIP database. Interactive dashboards have been constructed for use by programs to compare to the national cohort. Risk-adjusted multivariable analysis suggests that increased time in a technical skills lab was associated with increased success on the ABS\u27s Qualifying Examination, alone. Increased time in a technical skills lab and the presence of a formal teaching curriculum were associated with increased success on both the ABS\u27s Qualifying and Certifying Examination. Program type may be of some consequence in predicting success on the Qualifying Examination. CONCLUSIONS: The APDS has proved the concept that a highly secure database for the purpose of continuous risk-adjusted quality improvement in surgical education can be successfully deployed. EQIP will continue to improve and hopes to include an increasing number of programs as the barriers to participation are overcome

Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting

Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.Boston Children's Hospital (Frederick H. Lovejoy Fund)Harvard Global Health InstituteNational Institute of Allergy and Infectious Diseases (U.S.) (Grant AI100023)National Institute of Allergy and Infectious Diseases (U.S.) (Grant AI077883

Worldwide impacts of climate change on energy for heating and cooling

The energy sector is not only a major contributor to greenhouse gases, it is also vulnerable to climate change and will have to adapt to future climate conditions. The objective of this study is to analyze the impacts of changes in future temperatures on the heating and cooling services of buildings and the resulting energy and macro-economic effects at global and regional levels. For this purpose, the techno-economic TIAM-WORLD (TIMES Integrated Assessment Model) and the general equilibrium GEMINI-E3 (General Equilibrium Model of International-National Interactions between Economy, Energy and Environment) models are coupled with a climate model, PLASIM-ENTS (Planet-Simulator - Efficient Numerical Terrestrial Scheme). The key results are as follows. At the global level, the climate feedback induced by adaptation of the energy system to heating and cooling is found to be insignificant, partly because heating and cooling-induced changes compensate and partly because they represent a limited share of total final energy consumption. However, significant changes are observed at regional levels, more particularly in terms of addi- tional power capacity required to satisfy additional cooling services, resulting in increases in electricity prices. In terms of macro-economic impacts, welfare gains and losses are associated more with changes in energy exports and imports than with changes in energy consumption for heating and cooling. The rebound effect appears to be non-negligible. To conclude, the coupling of models of different nature was successful and showed that the energy and economic impacts of climate change on heating and cooling remain small at the global level, but changes in energy needs will be visible at more local scale

Pre-diagnostic leukocyte mitochondrial DNA copy number and colorectal cancer risk

Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case–control study of 324 female cases and 658 matched controls nested within the Nurses’ Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative polymerase chain reaction-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the fourth quartile, multivariable-adjusted OR [95% confidence interval (CI)] was 1.10 (0.69, 1.76) for the third quartile, 1.40 (0.89, 2.19) for the second quartile and 2.19 (1.43, 3.35) for the first quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest versus highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years’ follow-up, and marginally significant among those with ≥ 10 years’ follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis

Race, ethnicity, community-level socioeconomic factors, and risk of COVID-19 in the United States and the United Kingdom

BACKGROUND: There is limited prior investigation of the combined influence of personal and community-level socioeconomic factors on racial/ethnic disparities in individual risk of coronavirus disease 2019 (COVID-19). METHODS: We performed a cross-sectional analysis nested within a prospective cohort of 2,102,364 participants from March 29, 2020 in the United States (US) and March 24, 2020 in the United Kingdom (UK) through December 02, 2020 via the COVID Symptom Study smartphone application. We examined the contribution of community-level deprivation using the Neighborhood Deprivation Index (NDI) and the Index of Multiple Deprivation (IMD) to observe racial/ethnic disparities in COVID-19 incidence. ClinicalTrials.gov registration: NCT04331509. FINDINGS: Compared with non-Hispanic White participants, the risk for a positive COVID-19 test was increased in the US for non-Hispanic Black (multivariable-adjusted odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18–1.47) and Hispanic participants (OR, 1.42; 95% CI, 1.33–1.52) and in the UK for Black (OR, 1.17; 95% CI, 1.02–1.34), South Asian (OR, 1.39; 95% CI, 1.30–1.49), and Middle Eastern participants (OR, 1.38; 95% CI, 1.18–1.61). This elevated risk was associated with living in more deprived communities according to the NDI/IMD. After accounting for downstream mediators of COVID-19 risk, community-level deprivation still mediated 16.6% and 7.7% of the excess risk in Black compared to White participants in the US and the UK, respectively. INTERPRETATION: Our results illustrate the critical role of social determinants of health in the disproportionate COVID-19 risk experienced by racial and ethnic minorities. FUNDING: Please refer to the Funding section at the end of the article

Loss of LMO4 in the Retina Leads to Reduction of GABAergic Amacrine Cells and Functional Deficits

BACKGROUND: LMO4 is a transcription cofactor expressed during retinal development and in amacrine neurons at birth. A previous study in zebrafish reported that morpholino RNA ablation of one of two related genes, LMO4b, increases the size of eyes in embryos. However, the significance of LMO4 in mammalian eye development and function remained unknown since LMO4 null mice die prior to birth. METHODOLOGY/PRINCIPAL FINDINGS: We observed the presence of a smaller eye and/or coloboma in ∼40% LMO4 null mouse embryos. To investigate the postnatal role of LMO4 in retinal development and function, LMO4 was conditionally ablated in retinal progenitor cells using the Pax6 alpha-enhancer Cre/LMO4flox mice. We found that these mice have fewer Bhlhb5-positive GABAergic amacrine and OFF-cone bipolar cells. The deficit appears to affect the postnatal wave of Bhlhb5+ neurons, suggesting a temporal requirement for LMO4 in retinal neuron development. In contrast, cholinergic and dopaminergic amacrine, rod bipolar and photoreceptor cell numbers were not affected. The selective reduction in these interneurons was accompanied by a functional deficit revealed by electroretinography, with reduced amplitude of b-waves, indicating deficits in the inner nuclear layer of the retina. CONCLUSIONS/SIGNIFICANCE: Inhibitory GABAergic interneurons play a critical function in controlling retinal image processing, and are important for neural networks in the central nervous system. Our finding of an essential postnatal function of LMO4 in the differentiation of Bhlhb5-expressing inhibitory interneurons in the retina may be a general mechanism whereby LMO4 controls the production of inhibitory interneurons in the nervous system

Ad astra per aspera (Through Hardships to the Stars): Lessons Learned from the First National Virtual APDS Meeting, 2020

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective After COVID-19 rendered in-person meetings for national societies impossible in the spring of 2020, the leadership of the Association of Program Directors in Surgery (APDS) innovated via a virtual format in order to hold its national meeting. Design APDS leadership pre-emptively considered factors that would be important to attendees including cost, value, time, professional commitments, education, sharing of relevant and current information, and networking. Setting The meeting was conducted using a variety of virtual formats including a web portal for entry, pre-ecorded poster and oral presentations on the APDS website, interactive panels via a web conferencing platform, and livestreaming. Participants There were 298 registrants for the national meeting of the APDS, and 59 participants in the New Program Directors Workshop. The registrants and participants comprised medical students, residents, associate program directors, program directors, and others involved in surgical education nationally. Results There was no significant difference detected for high levels of participant satisfaction between 2019 and 2020 for the following items: overall program rating, topics and content meeting stated objectives, relevant content to educational needs, educational format conducive to learning, and agreement that the program will improve competence, performance, communication skills, patient outcomes, or processes of care/healthcare system performance. Conclusions A virtual format for a national society meeting can provide education, engagement, and community, and the lessons learned by the APDS in the process can be used by other societies for utilization and further improvement

Integrative multi-omics module network inference with Lemon-Tree

Module network inference is an established statistical method to reconstruct co-expression modules and their upstream regulatory programs from integrated multi-omics datasets measuring the activity levels of various cellular components across different individuals, experimental conditions or time points of a dynamic process. We have developed Lemon-Tree, an open-source, platform-independent, modular, extensible software package implementing state-of-the-art ensemble methods for module network inference. We benchmarked Lemon-Tree using large-scale tumor datasets and showed that Lemon-Tree algorithms compare favorably with state-of-the-art module network inference software. We also analyzed a large dataset of somatic copy-number alterations and gene expression levels measured in glioblastoma samples from The Cancer Genome Atlas and found that Lemon-Tree correctly identifies known glioblastoma oncogenes and tumor suppressors as master regulators in the inferred module network. Novel candidate driver genes predicted by Lemon-Tree were validated using tumor pathway and survival analyses. Lemon-Tree is available from http://lemon-tree.googlecode.com under the GNU General Public License version 2.0.Comment: minor revision; 13 pages text + 4 figures + 4 tables + 4 pages supplementary methods; supplementary tables available from the author

Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.Peer reviewe