Publications by authors named "John Green"

278 Publications

Intracerebellar infusion of an mGluR1/5 agonist enhances eyeblink conditioning.

Behav Neurosci 2021 Feb 25. Epub 2021 Feb 25.

Neuroscience Graduate Program, University of Vermont.

Cerebellar metabotropic glutamate receptor 1 (mGluR1) expressed by Purkinje cells may play an important role in learning-related cerebellar plasticity. Eyeblink conditioning (EBC) is a well-studied form of Pavlovian learning that engages discrete areas of cerebellar cortex and deep cerebellar nuclei. EBC is impaired in mGluR1 knockout mice. Here, we show that infusion of the mGluR1/5 agonist DHPG into the lobulus simplex region of cerebellar cortex facilitates EBC in rats. Infusion was made prior to Sessions 1 and 2 of EBC but the facilitatory effects persisted throughout subsequent, noninfusion sessions. The facilitatory effects were confined to frequency of eyeblink conditioned responses (CRs); there were no effects on amplitude or latency of CRs. There were also no effects on reflexive responding to the tone conditioned stimulus or eyelid stimulation unconditioned stimulus. The current results provide further evidence that cerebellar mGluR1 plays a role in cerebellar-dependent associative learning and complement previous studies using mGluR1 knockout mice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/bne0000429DOI Listing
February 2021

LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors.

Clin Cancer Res 2020 Dec 22. Epub 2020 Dec 22.

Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.

Purpose: Targeting RAF for antitumor therapy in RAS-mutant tumors holds promise. Herein, we describe in detail novel properties of the type II RAF inhibitor, LXH254.

Experimental Design: LXH254 was profiled in biochemical, , and assays, including examining the activities of the drug in a large panel of cancer-derived cell lines and a comprehensive set of models. In addition, activity of LXH254 was assessed in cells where different sets of RAF paralogs were ablated, or that expressed kinase-impaired and dimer-deficient variants of ARAF.

Results: We describe an unexpected paralog selectivity of LXH254, which is able to potently inhibit BRAF and CRAF, but has less activity against ARAF. LXH254 was active in models harboring BRAF alterations, including atypical BRAF alterations coexpressed with mutant K/NRAS, and mutants, but had only modest activity in mutants. In RAS-mutant lines, loss of ARAF, but not BRAF or CRAF, sensitized cells to LXH254. ARAF-mediated resistance to LXH254 required both kinase function and dimerization. Higher concentrations of LXH254 were required to inhibit signaling in RAS-mutant cells expressing only ARAF relative to BRAF or CRAF. Moreover, specifically in cells expressing only ARAF, LXH254 caused paradoxical activation of MAPK signaling in a manner similar to dabrafenib. Finally, , LXH254 drove complete regressions of isogenic variants of RAS-mutant cells lacking ARAF expression, while parental lines were only modestly sensitive.

Conclusions: LXH254 is a novel RAF inhibitor, which is able to inhibit dimerized BRAF and CRAF, as well as monomeric BRAF, while largely sparing ARAF.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2563DOI Listing
December 2020

Differential effects of two early life stress paradigms on cerebellar-dependent delay eyeblink conditioning.

Neurobiol Stress 2020 Nov 17;13:100242. Epub 2020 Jul 17.

Department of Psychological Science, University of Vermont, Burlington, VT, United States.

Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2-9, n = 15) and maternal separation (60 min per day during postnatal day 2-14, n = 13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.
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http://dx.doi.org/10.1016/j.ynstr.2020.100242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739029PMC
November 2020

A Proof of Concept for Biomarker-Guided Targeted Therapy against Ovarian Cancer Based on Patient-Derived Tumor Xenografts.

Cancer Res 2020 10 3;80(19):4278-4287. Epub 2020 Aug 3.

Laboratory of Systems Pharmacology, Harvard Medical School, Boston, Massachusetts.

Advanced ovarian cancers are a leading cause of cancer-related death in women and are currently treated with surgery and chemotherapy. This standard of care is often temporarily successful but exhibits a high rate of relapse, after which, treatment options are few. Here we investigate whether biomarker-guided use of multiple targeted therapies, including small molecules and antibody-drug conjugates, is a viable alternative. A panel of patient-derived ovarian cancer xenografts (PDX), similar in genetics and chemotherapy responsiveness to human tumors, was exposed to 21 monotherapies and combination therapies. Three monotherapies and one combination were found to be active in different subsets of PDX. Analysis of gene expression data identified biomarkers associated with responsiveness to each of the three targeted therapies, none of which directly inhibits an oncogenic driver. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. The distribution of biomarker positivity in The Cancer Genome Atlas data suggests the potential for a similar precision approach in human patients. SIGNIFICANCE: This study exploits a panel of patient-derived xenografts to demonstrate that most ovarian tumors can be matched to effective biomarker-guided treatments.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541581PMC
October 2020

Distractions During Patient Handoff: The Application-Based Messaging Volume on General Surgery Interns.

J Surg Educ 2020 Nov - Dec;77(6):e201-e208. Epub 2020 Jul 20.

Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina. Electronic address:

Objective: Mobile phone-based paging systems have become increasingly common for communication within hospitals. Surgical interns receive the most pages, and our aim is to objectively quantify and evaluate this burden to allow for targeted improvement.

Design: We performed a retrospective review of our institutions mobile phone-based paging system data (Halo Health, Cincinnati, OH) from July 2019 to September 2019.

Setting: Carolinas Medical Center, Charlotte, NC, USA.

Participants: Seven general surgery postgraduate year (PGY) 1 residents.

Results: Forty-five thousand eight hundred and one messages met inclusion criteria, with 27,397 messages received and 18,404 sent. PGY 1 residents each received an average of 48 ± 41 messages per shift, with 8 ± 17 messages per day while off-duty. Night shifts averaged more messages than day shifts (80 ± 39 vs 38 ± 32, p < 0.0001), and had more shifts with high message volume (30% vs 11%, p = 0.0005). Evaluating the total number of messages received per minute of the day, the largest number of high-volume message intervals (21) occurred during patient handoff (1700-1900 hours). Most messages were sent by nursing staff (55.8%), followed by medical providers (38.2%).

Conclusions: PGY 1 residents receive a large number of pages using a messaging application, with many occurring at critical times. Residents received a higher volume of pages on night shifts, during patient handoff, and while off-duty. Since most pages are from nursing staff, targeted education and preventative actions may help decrease the volume of pages during these critical times.
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http://dx.doi.org/10.1016/j.jsurg.2020.06.032DOI Listing
July 2020

Rural Population Health and Aging: Toward a Multilevel and Multidimensional Research Agenda for the 2020s.

Am J Public Health 2020 09 16;110(9):1328-1331. Epub 2020 Jul 16.

Leif Jensen is with the Population Research Institute, Pennsylvania State University, University Park. Shannon M. Monnat is with the Lerner Center for Public Health Promotion, Syracuse University, Syracuse, NY. John J. Green is with the Center for Population Studies, University of Mississippi, University. Lori M. Hunter is with the University of Colorado Population Center, University of Colorado, Boulder. Martin J. Sliwinski is with the Center for Healthy Aging, Pennsylvania State University.

The unique health and aging challenges of rural populations often go unnoticed. In fact, the rural United States is home to disproportionate shares of older and sicker people, there are large and growing rural-urban and within-rural mortality disparities, many rural communities are in population decline, and rural racial/ethnic diversity is increasing.Yet rural communities are not monolithic, and although some rural places are characterized by declining health, others have seen large improvements in population health. We draw on these realities to call for new research in five areas.First, research is needed to better describe health disparities between rural and urban areas and, because rural places are not monolithic, across rural America. Second, research is needed on how trends in rural population health and aging are affecting rural communities. Third, research is needed on the ways in which economic well-being and livelihood strategies interact with rural health and aging. Fourth, we need to better understand the health implications of the physical and social isolation characterizing many rural communities. Finally, we argue for new research on the implications of local natural environments and climate change for rural population health and aging.
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http://dx.doi.org/10.2105/AJPH.2020.305782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427233PMC
September 2020

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

Ann Surg 2020 09;272(3):469-478

University of Kentucky, Lexington, Kentucky.

Background And Objective: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI.

Methods: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding.

Results: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ± 15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ± 2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP.

Conclusion: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.
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http://dx.doi.org/10.1097/SLA.0000000000004102DOI Listing
September 2020

Surgery Residents Spend Nearly 8 Months of Their 5-Year Training on the Electronic Health Record (EHR).

J Surg Educ 2020 Nov - Dec;77(6):e237-e244. Epub 2020 Jul 10.

Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina. Electronic address:

Objective: Electronic health records (EHRs) are an integral part of the medical system and are used in all aspects of care. Despite multiple advantages of an EHR, concerns exist over the amount of time that residents spend on computers rather than in direct patient care. This study aims to quantify the time a general surgery resident spends on the EHR during their training.

Design/participants: Active usage time data from our institution's EHR were extracted for 34 unique general surgery residents from October 2014 to June 2019. Career time on the EHR was calculated and a "work month" was defined as a 4-week period of 80 hours per week.

Setting: Carolinas Medical Center, Charlotte, NC.

Results: Total career EHR usage for a general surgery resident was 2512 continuous hours, corresponding to 31.4 work weeks or 7.9 work months. In total, 7133 charts were opened with an average of 20.5 minutes on the EHR per patient chart. Career time spent on specific tasks included: chart review 10.6 work weeks, documentation 10.4 work weeks, and order entry 5.4 work weeks. The total number of orders entered were 57,739 and total number of documents created were 9222. EHR time in all aspects, patient charts opened, documents created, and number of orders entered decreased as postgraduate year increased.

Conclusions: This is the first study quantifying the total time a general surgery resident spends on the EHR during their clinical training. Total EHR time equated to nearly 8 work months. General surgery residents spend considerable time on the EHR and this underscores the importance of implementing methods to improve EHR efficiency and maximize time for clinical training.
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http://dx.doi.org/10.1016/j.jsurg.2020.06.017DOI Listing
July 2020

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

J Surg Educ 2020 Nov - Dec;77(6):1465-1472. Epub 2020 Jul 6.

Department of Surgery, Warren Alport School of Medicine, Brown University, Providence, Rhode Island.

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.
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http://dx.doi.org/10.1016/j.jsurg.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336917PMC
December 2020

Ibuprofen: Fish Short-Term Reproduction Assay with Zebrafish (Danio rerio) Based on an Extended OECD 229 Protocol.

Environ Toxicol Chem 2020 08 8;39(8):1534-1545. Epub 2020 Jul 8.

Eurofins Agroscience Services, Easton, Maryland, USA.

A study was conducted to understand the potential for ibuprofen to impact the hypothalamus-pituitary-gonadal endocrine axis resulting in disruption of fish reproduction. The Good Laboratory Practice study was conducted according to the Organisation for Economic Co-operation and Development 229 Protocol, Fish Short-Term Reproduction Assay, and extended an additional 4 d to evaluate hatching success in the F1 generation. Test organisms were exposed to nominal test concentrations of 0.5, 2.4, 11.5, 55.3, and 265.4 µg ibuprofen/L and a negative control (dilution water). To strengthen the statistical power of the study, twice the number of replicates were used in the negative control versus individual treatment levels. A 21-d pre-exposure to identify groups of actively spawning fish was immediately followed by a 36-d exposure. Results for apical endpoints of survival, growth, and reproduction (fecundity and fertility), as well as the biomarker vitellogenin in the F0 generation and time to hatch and hatching success in the F1 generation are presented. Based on mean measured exposure concentrations and effects on fecundity in the F0 generation and hatching success in the F1 generation, overall no-observed-effect concentration and lowest-observed-effect concentration for the present study were 55.2 and 265.9 µg ibuprofen/L, respectively. Results from the present study indicate a lack of endocrine-mediated reproductive effects in zebrafish at environmentally relevant concentrations of ibuprofen. Environ Toxicol Chem 2020;39:1534-1545. © 2020 SETAC.
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http://dx.doi.org/10.1002/etc.4742DOI Listing
August 2020

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress.

Sci Rep 2020 04 29;10(1):7236. Epub 2020 Apr 29.

Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.

Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions.
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http://dx.doi.org/10.1038/s41598-020-64075-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190863PMC
April 2020

Investigation of ward fidelity to a multicomponent delirium prevention intervention during a multicentre, pragmatic, cluster randomised, controlled feasibility trial.

Age Ageing 2020 07;49(4):648-655

Academic Unit for Ageing and Stroke Research, University of Leeds, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.

Background: delirium is a frequent complication of hospital admission for older people and can be reduced by multicomponent interventions, but implementation and delivery of such interventions is challenging.

Objective: to investigate fidelity to the prevention of delirium system of care within a multicentre, pragmatic, cluster randomised, controlled feasibility trial.

Setting: five care of older people and three orthopaedic trauma wards in eight hospitals in England and Wales.

Data Collection: research nurse observations of ward practice; case note reviews and examination of documentation.

Assessment: 10 health care professionals with experience in older people's care assessed the fidelity to 21 essential implementation components within four domains: intervention installation (five items; maximum score = 5); intervention delivery (12 items; maximum score = 48); intervention coverage (three items; maximum score = 16); and duration of delivery (one item; maximum score = 1).

Results: the mean score (range) for each domain was: installation 4.5 (3.5-5); delivery 32.6 (range 27.3-38.3); coverage 7.9 (range 4.2-10.1); and duration 0.38 (0-1). Of the 10 delirium risk factors, infection, nutrition, hypoxia and pain were the most and cognitive impairment, sensory impairment and multiple medications the least consistently addressed. Overall fidelity to the intervention was assessed as high (≥80%) in two wards, medium (51-79%) in five wards and low (≤50%) in one ward.

Conclusion: the trial was designed as a pragmatic evaluation, and the findings of medium intervention fidelity are likely to be generalisable to delirium prevention in routine care and provide an important context to interpret the trial outcomes.
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http://dx.doi.org/10.1093/ageing/afaa042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331099PMC
July 2020

A multicentre, pragmatic, cluster randomised, controlled feasibility trial of the POD system of care.

Age Ageing 2020 07;49(4):640-647

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Objective: to provide a preliminary estimate of the effectiveness of the prevention of delirium (POD) system of care in reducing incident delirium in acute hospital wards and gather data for a future definitive randomised controlled trial.

Design: cluster randomised and controlled feasibility trial.

Setting: sixteen acute care of older people and orthopaedic trauma wards in eight hospitals in England and Wales.

Participants: patients 65 years and over admitted to participating wards during the trial period.

Interventions: participating wards were randomly assigned to either the POD programme or usual care, determined by existing local policies and practices. The POD programme is a manualised multicomponent delirium prevention intervention that targets 10 risk factors for delirium. The intervention wards underwent a 6-month implementation period before trial recruitment commenced. Main outcome measure incidence of new-onset delirium measured using the Confusion Assessment Method (CAM) measured daily for up to 10 days post consent.

Results: out of 4449, 3274 patients admitted to the wards were eligible. In total, 714 patients consented (713 registered) to the trial, thirty-three participants (4.6%) withdrew. Adherence to the intervention was classified as at least medium for seven wards. Rates of new-onset delirium were lower than expected and did not differ between groups (24 (7.0%) of participants in the intervention group versus 33 (8.9%) in the control group; odds ratio (95% confidence interval) 0.68 (0.37-1.26); P = 0.2225).

Conclusions: based on these findings, a definitive trial is achievable and would need to recruit 5220 patients in 26 two-ward hospital clusters. Trial registration: ISRCTN01187372. Registered 13 March 2014.
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http://dx.doi.org/10.1093/ageing/afaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331094PMC
July 2020

Surgery Resident Time Consumed by the Electronic Health Record.

J Surg Educ 2020 Sep - Oct;77(5):1056-1062. Epub 2020 Apr 16.

Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, North Carolina. Electronic address:

Objective: Time spent on the Electronic Health Record (EHR) influences surgical residents' clinical availability. Objective data assessing EHR usage among surgical residents are lacking and necessary.

Design/participants: Active EHR usage data for 70 surgical residents were collected from April 2015 through April 2016. Active EHR usage was defined as more than 15 keystrokes, or 3 mouse clicks, or 1700 "mouse miles" per minute. Usage data of different specialties, interns (PGY 1), juniors (PGY 2, 3), and seniors (PGY 4, 5) were compared.

Setting: Carolinas Medical Center, Charlotte, NC.

Results: Interns spent more time than juniors on total EHR activities per day (134.5 vs 105.5 minutes, p < 0.001) and juniors spent more time per day than seniors (105.5 vs 78.7 minutes, p < 0.001). Among different EHR activities per patient, interns spent greater time than juniors on chart review (8.1 vs 6.2 minutes, p < 0.001), documentation (9.0 vs 6.5 minutes, p < 0.001), and orders (3.6 vs 3.0 minutes, p < 0.001). Juniors spent the same time as seniors on chart review (6.2 vs 6.5 minutes, p = 0.2). Juniors spent more time than seniors on documentation (6.5 vs 5.2 minutes, p < 0.001) and orders (3.0 vs 2.7 minutes, p < 0.05). Comparing EHR activities per patient among different specialties, General Surgery residents spent more time than Orthopedic residents on total EHR time (19.9 vs 15.9 minutes, p < 0.001), chart review (6.8 vs 5.7 minutes, p < 0.001), documentation (6.3 vs 5.6 minutes, p < 0.001), and orders (3.6 vs 2.6 minutes, p < 0.001). General Surgery residents spent less time than OB/GYN residents on total EHR time (19.9 vs 22 minutes, p < 0.01), chart review (6.8 vs. 7.5 minutes, p < 0.05), and documentation (6.3 vs 7.6 minutes, p < 0.001), but more time on orders (3.6 vs 2.9 minutes, p < 0.001).

Conclusions: These are the first reported objective findings on surgical resident use of the EHR and may provide an opportunity for improvement in EHR training and usage.
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http://dx.doi.org/10.1016/j.jsurg.2020.03.008DOI Listing
April 2020

Maximizing the Calm before the Storm: Tiered Surgical Response Plan for Novel Coronavirus (COVID-19).

J Am Coll Surg 2020 06 30;230(6):1080-1091.e3. Epub 2020 Mar 30.

Division of Acute Care Surgery, Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC.

The novel coronavirus (COVID-19) was first diagnosed in Wuhan, China in December 2019 and has now spread throughout the world, being verified by the World Health Organization as a pandemic on March 11. This had led to the calling of a national emergency on March 13 in the US. Many hospitals, healthcare networks, and specifically, departments of surgery, are asking the same questions about how to cope and plan for surge capacity, personnel attrition, novel infrastructure utilization, and resource exhaustion. Herein, we present a tiered plan for surgical department planning based on incident command levels. This includes acute care surgeon deployment (given their critical care training and vertically integrated position in the hospital), recommended infrastructure and transfer utilization, triage principles, and faculty, resident, and advanced care practitioner deployment.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128345PMC
June 2020

Underrepresented Minorities in General Surgery Residency: Analysis of Interviewed Applicants, Residents, and Core Teaching Faculty.

J Am Coll Surg 2020 Jul 7;231(1):54-58. Epub 2020 Mar 7.

Department of Surgery, Maine Medical Center, Portland, ME.

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires diversity in residency. The self-identified race/ethnicities of general surgery applicants, residents, and core teaching faculty were assessed to evaluate underrepresented minority (URM) representation in surgery residency programs and to determine the impact of URM faculty and residents on URM applicants' selection for interview or match.

Study Design: Data from the 2018 application cycle were collated for 10 general surgery programs. Applicants without a self-identified race/ethnicity were excluded. URMs were defined as those identifying as black/African American, Hispanic/Latino/of Spanish origin, and American Indian/Alaskan Native/Native Hawaiian/Pacific Islander-Samoan. Statistical analyses included chi-square tests and a multivariate model.

Results: Ten surgery residency programs received 9,143 applications from 3,067 unique applicants. Applications from white, Asian, Hispanic/Latino, black/African American, and American Indian applicants constituted 66%, 19%, 8%, 7% and 1%, respectively, of those applications selected to interview and 66%, 13%, 11%, 8%, and 2%, respectively, of applications resulting in a match. Among programs' 272 core faculty and 318 current residents, 10% and 21%, respectively, were identified as URMs. As faculty diversity increased, there was no difference in selection to interview for URM (odds ratio [OR] 0.83; 95% CI 0.54 to 1.28, per 10% increase in faculty diversity) or non-URM applicants (OR 0.68; 95% CI 0.57 to 0.81). Similarly, greater URM representation among current residents did not affect the likelihood of being selected for an interview for URM (OR 1.20; 95%CI 0.90 to 1.61) vs non-URM applicants (OR 1.28; 95% CI 1.13 to 1.45). Current resident and faculty URM representation was correlated (r = 0.8; p = 0.005).

Conclusions: Programs with a greater proportion of URM core faculty or residents did not select a greater proportion of URM applicants for interview. However, core faculty and resident racial diversity were correlated. Recruitment of racially/ethnically diverse trainees and faculty will require ongoing analysis to develop effective recruitment strategies.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.02.042DOI Listing
July 2020

Inactivation of the prelimbic cortex attenuates operant responding in both physical and behavioral contexts.

Neurobiol Learn Mem 2020 05 14;171:107189. Epub 2020 Feb 14.

Department of Psychological Science, University of Vermont, Burlington, VT 05405, United States. Electronic address:

The present experiments aimed to expand our understanding of the role of the prelimbic cortex (PL) in the contextual control of instrumental behavior. Research has previously shown that the PL is involved when the "physical context," or chamber in which an instrumental behavior is trained, facilitates performance of the instrumental response (Trask, Shipman, Green, & Bouton, 2017). Recently, evidence has suggested that when a sequence of two instrumental behaviors is required to earn a reinforcing outcome, the first response (rather than the physical chamber) can be the "behavioral context" for the second response (Thrailkill, Trott, Zerr, and Bouton, 2016). Could the PL also be involved in this kind of contextual control? Here rats first learned a heterogenous behavior chain in which the first response (i.e., pressing a lever or pulling a chain) was cued by a discriminative stimulus and led to a second stimulus which cued a second response (i.e., pulling a chain or pressing a lever); the second response led to a sucrose reward. When the first and second responses were tested in isolation in the training context, pharmacological inactivation of the PL resulted in a reduction of the first response, but not the second response. When the second response was performed in the "context" of the first response (i.e., as part of the behavior chain) however, PL inactivation reduced the second response. Overall, these results support the idea that the PL is important for mediating the effects of a training context on instrumental responding, whether the context is physical or behavioral.
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http://dx.doi.org/10.1016/j.nlm.2020.107189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198320PMC
May 2020

Some factors that restore goal-direction to a habitual behavior.

Neurobiol Learn Mem 2020 03 9;169:107161. Epub 2020 Jan 9.

University of Vermont, United States. Electronic address:

Recent findings from our laboratory suggest that an extensively-practiced instrumental behavior can appear to be a goal-directed action (rather than a habit) when a second behavior is added and reinforced during intermixed final sessions (Shipman et al., 2018). The present experiments were designed to explore and understand this finding. All used the taste aversion method of devaluing the reinforcer to distinguish between goal-directed actions and habits. Experiment 1 confirmed that reinforcing a second response in a separate context (but not mere exposure to that context) can return an extensively-trained habit to the status of goal-directed action. Experiment 2 showed that training of the second response needs to be intermixed with training of the first response to produce this effect; training the second response after the first-response training was complete preserved the first response as a habit. Experiment 3 demonstrated that reinforcing the second response with a different reinforcer breaks the habit status of the first response. Experiment 4 found that free reinforcers (that were not response-contingent) were sufficient to restore goal-directed performance. Together, the results suggest that unexpected reinforcer delivery can render a habitual response goal-directed again.
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http://dx.doi.org/10.1016/j.nlm.2020.107161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787053PMC
March 2020

Effects of an Acute Strength and Conditioning Training Session on Dual-Energy X-Ray Absorptiometry Results.

J Strength Cond Res 2020 Apr;34(4):901-904

Department of Health and Kinesiology, Texas A&M University, College Station, Texas.

Lytle, JR, Stanelle, ST, Kravits, DM, Ellsworth, RL, Martin, SE, Green, JS, and Crouse, SF. Effects of an acute strength and conditioning training session on dual-energy x-ray absorptiometry results. J Strength Cond Res 34(4): 901-904, 2020-The purpose of this study was to determine whether an athletic strength and conditioning (S&C) session will alter body composition estimates of a dual-energy x-ray absorptiometry (DXA) scan. Twenty-two strength-trained individuals (15 men, 7 women, 24 ± 2 years, 174.2 ± 8.5 cm, 83.5 ± 15.0 kg) volunteered to participate in the study. Each subject underwent 2 DXA scans, before and after completion of the S&C session, which consisted of upper- and lower-body resistance exercises and interval running. Subjects consumed a free-living meal before the first scan, after which only ad libitum water intake was consumed until completing the second scan. Results were analyzed through sex by time repeated-measures analysis of variance. If no interaction effect was observed, results were next analyzed through correlated t-test (α = 0.05). Significant sex by time interactions were observed for arm total and lean mass, as well as a significant main effect of time showing a decrease in arm lean mass after the S&C session. Values before and after the S&C session that resulted in significant differences via correlated t-test are displayed in Table 1. Results revealed a significant decrease in total mass, arm and leg percent fat, and trunk lean mass, and an increase in leg lean mass.
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http://dx.doi.org/10.1519/JSC.0000000000003504DOI Listing
April 2020

Process of implementing and delivering the Prevention of Delirium system of care: a mixed method preliminary study.

BMC Geriatr 2019 12 31;20(1). Epub 2019 Dec 31.

Academic Unit of Elderly Care and Rehabilitation, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, West Yorkshire, UK.

Background: Delirium is a frequent complication of hospital admission among older people. Multicomponent interventions which can reduce incident delirium by ≈one-third are recommended by the National Institute of Health and Care Excellence. Currently, a standardised delirium prevention system of care suitable for adoption in the UK National Health Service does not exist. The Prevention of Delirium (POD) system of care is a theory informed, multicomponent intervention and systematic implementation process which includes a role for hospital volunteers. We report POD implementation and delivery processes in NHS hospital wards, as part of a feasibility study.

Methods: A comparative case study design and participatory, multi-method evaluation was performed with sequential six month preparatory and six month delivery stages. Six wards in five hospitals in Northern England were recruited. Methods included: facilitated workshops; observation of POD preparatory activities; qualitative interviews with staff; collection of ward organisational and patient profiles; and structured observation of staff workload.

Results: POD implementation and delivery was fully accomplished in four wards. On these wards, implementation strategies informed by Normalization Process Theory operated synergistically and cumulatively. An interactive staff training programme on delirium and practices that might prevent it among those at risk, facilitated purposeful POD engagement. Observation of practice juxtaposed to action on delirium preventive interventions created tension for change, legitimating new ways of organising work around it. Establishing systems, processes and documentation to make POD workable in the ward setting, enhanced staff ownership. 'Negotiated experimentation' to involve staff in creating, appraising and modifying systems and practices, helped integrate the POD care system in ward routines. Activating these change mechanisms required a particular form of leadership: pro-active 'steer', and senior ward 'facilitator' to extend 'reach' to the staff group. Organisational discontinuity (i.e. ward re-location and re-modelling) disrupted and extended POD implementation; staff shortages adversely affected staff capacity to invest in POD. Findings resulted in the development of 'site readiness' criteria without which implementation of this complex intervention was unlikely to occur.

Conclusions: POD implementation and delivery is feasible in NHS wards, but a necessary context for success is 'site readiness.'
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http://dx.doi.org/10.1186/s12877-019-1374-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938603PMC
December 2019

Metabolic Basis for Nonlinearity in 1,3-Dichloropropene Toxicokinetics and Use in Setting a Kinetically-derived Maximum Inhalation Exposure Concentration in Mice.

Toxicol Sci 2020 03;174(1):16-24

Corteva AgriscienceTM, Research and Development, Indianapolis, Indiana.

1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.
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http://dx.doi.org/10.1093/toxsci/kfz241DOI Listing
March 2020

Rare Orbital Metastasis Originating From a Neuroendocrine Tumor.

Radiol Technol 2019 Nov;91(2):112-119

Background: This case study details a rare orbital metastasis originating from the gastrointestinal tract. A patient presented with proptosis of the right eye precipitated by a slow-growing orbital tumor. A biopsy confirmed a low-grade neuroendocrine tumor. Imaging studies were completed, with magnetic resonance (MR) imaging of the orbits providing the most detailed images of the mass. Fusion software images were created from the MR images and indium In 111 pentetreotide (octreoscan) studies, which confirmed the presence of the neuroendocrine carcinoid tumor.

Discussion: Orbital metastases are a rare condition associated with various symptoms, most commonly proptosis and diplopia. Imaging modalities, such as MR, computed tomography, and nuclear medicine technology, are instrumental in detecting and assessing these masses. Fusion imaging software can provide additional opportunities for facilities without hybrid scanners. The treatment of choice for orbital metastases is octreotide therapy; however, radiation therapy, partial or complete surgical removal of the tumor, and chemotherapy also are used.

Conclusion: Traditional imaging techniques and fusion imaging techniques are essential for diagnosing and treating orbital metastases.
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November 2019

Impacts of deletion and ichthyosis prematurity syndrome-associated mutations in fatty acid transport protein 4 on the function of RPE65.

FEBS Lett 2020 02 20;594(3):540-552. Epub 2019 Oct 20.

Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, LA, USA.

The retinal pigment epithelium-specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65-catalyzed synthesis of 11-cis-retinol from all-trans-retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE65 and the impacts of IPS-associated FATP4 mutations on RPE65 expression, 11-cis-retinol synthesis, and all-trans-retinyl ester synthesis. Our results suggest that the interaction between FATP4 and RPE65 contributes to the inhibition of RPE65 function and that IPS-associated nonsense and missense mutations in FATP4 have different effects on the visual cycle.
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http://dx.doi.org/10.1002/1873-3468.13633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012757PMC
February 2020

How to pass the emergency OSCE station.

BMJ 2019 Oct 1;367:l2414. Epub 2019 Oct 1.

Cardiff and Vale University Health Board, UK.

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http://dx.doi.org/10.1136/sbmj.l2414DOI Listing
October 2019

Chemogenetic Silencing of Prelimbic Cortex to Anterior Dorsomedial Striatum Projection Attenuates Operant Responding.

eNeuro 2019 Sep/Oct;6(5). Epub 2019 Oct 22.

Department of Psychological Science

Operant (instrumental) conditioning is a laboratory analog for voluntary behavior and involves learning to make a response for a reinforcing outcome. The prelimbic cortex (PL), a region of the rodent medial prefrontal cortex, and the dorsomedial striatum (DMS), have been separately established as important in the acquisition of minimally-trained operant behavior. Despite dense anatomical connections between the two regions, experimenters have only recently linked projections from the PL to the posterior DMS (pDMS) in the acquisition of an operant response. Yet, it is still unknown if these projections mediate behavioral expression, and if more anterior regions of the DMS (aDMS), which receive dense projections from the PL, are also involved. Therefore, we utilized designer receptors exclusively activated by designer drugs (DREADDs) to test whether or not projections from the PL to the aDMS influence the expression of operant behavior. Rats underwent bilateral PL-targeted infusions of either a DREADD virus (AAV8-hSyn-hM4D(Gi)-mCherry) or a control virus (AAV8-hSyn-GFP). In addition, guide cannulae were implanted bilaterally in the aDMS. Rats were tested with both clozapine-N-oxide (CNO) (DREADD ligand) and vehicle infusions into the aDMS. Animals that had received the DREADD virus, but not the control virus, showed attenuated responding when they received CNO microinfusions into the aDMS, compared to vehicle infusions. Patch clamp electrophysiology verified the inhibitory effect of CNO on DREADDs-expressing PL neurons in acute brain slices. GFP-expressing control PL neurons were unaffected by CNO. The results add to the recent literature suggesting that connections between the PL and aDMS are important for the expression of minimally-trained operant responding.
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http://dx.doi.org/10.1523/ENEURO.0125-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817716PMC
May 2020

Author's Reply.

Integr Environ Assess Manag 2019 07;15(4):497-498

DuPont, Wilmington, Delaware, USA.

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http://dx.doi.org/10.1002/ieam.4172DOI Listing
July 2019

Multicentre randomised controlled trial comparing standard and high resolution optical technologies in colorectal cancer screening.

Frontline Gastroenterol 2019 Jul 26;10(3):244-252. Epub 2019 Feb 26.

GI Services, University College London Hospitals NHS Foundation Trust, London, UK.

Background And Objectives: The UK bowel cancer screening programme (BCSP) has been established for the early detection of colorectal cancer offering colonoscopy to patients screened positive by faecal occult blood tests. In this multisite, prospective, randomised controlled trial, we aimed to compare the performance of Standard Definition Olympus Lucera (SD-OL) with Scope Guide and the High Definition Pentax HiLine (HD-PHL).

Patients And Methods: Subjects undergoing a colonoscopy as part of the UK National BCSP at four UK sites were randomised to an endoscopy list run using either SD-OL or HD-PHL. Primary endpoints were polyp and adenoma detection rate (PDR and ADR, respectively) as well as polyp size, morphology and histology characteristics.

Results: 262 subjects (168 males, mean age 66.3±4.3 years) were colonoscoped (133 patients with HD-PHL while 129 with SD-OL). PDR and ADR were comparable within the two optical systems. The HD-PHL group resulted in a PDR 55.6% and ADR 43.6%; the SD-OL group had PDR 56.6% and ADR 45.7%. HD-PHL was significantly superior to SD-OL in detection of flat adenomas (18.6% vs 5.2%, p<0.001), but not detection of pedunculated or sessile polyps. Patient comfort, use of sedation and endoscopist perception of procedural difficulty resulted similar despite the use of Scope Guide with SD-OL.

Conclusion: PDR and ADR were not significantly different between devices. The high-resolution colonoscopy system HD-PHL may improve polyp detection as compared with standard resolution technology in detecting flat adenomas. This advantage may have clinically significant implications for missed lesion rates and post-colonoscopy interval colorectal cancer rates.
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http://dx.doi.org/10.1136/flgastro-2018-101130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583579PMC
July 2019

Impact of the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) on endoscopy services in the UK and beyond.

Frontline Gastroenterol 2019 Apr 13;10(2):93-106. Epub 2018 Nov 13.

Joint Advisory Group on Gastrointestinal Endoscopy, Royal College of Physicians, London, UK.

The Joint Advisory Group on Gastrointestinal Endoscopy (JAG) was initially established in 1994 to standardise endoscopy training across specialties. Over the last two decades, the position of JAG has evolved to meet its current role of quality assuring all aspects of endoscopy in the UK to provide the highest quality, patient-centred care. Drivers such as changes to healthcare agenda, national audits, advances in research and technology and the advent of population-based cancer screening have underpinned this shift in priority. Over this period, JAG has spearheaded various quality assurance initiatives with support from national stakeholders. These have led to the achievement of notable milestones in endoscopy quality assurance, particularly in the three major areas of: (1) endoscopy training, (2) accreditation of endoscopy services (including the Global Rating Scale), and (3) accreditation of screening endoscopists. These developments have changed the landscape of UK practice, serving as a model to promote excellence in endoscopy. This review provides a summary of JAG initiatives and assesses the impact of JAG on training and endoscopy services within the UK and beyond.
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http://dx.doi.org/10.1136/flgastro-2018-100969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540274PMC
April 2019

Underrepresented Minorities are Underrepresented Among General Surgery Applicants Selected to Interview.

J Surg Educ 2019 Nov - Dec;76(6):e15-e23. Epub 2019 Jun 5.

Maine Medical Center, Portland, Maine.

Objective: Diversity is an ill-defined entity in general surgery training. The Accreditation Council for Graduate Medical Education recently proposed new common program requirements including verbiage requiring diversity in residency. "Recruiting" for diversity can be challenging within the constraints of geographic preference, type of program, and applicant qualifications. In addition, the Match process adds further uncertainty. We sought to study the self-identified racial/ethnic distribution of general surgery applicants to better ascertain the characteristics of underrepresented minorities (URM) within the general surgery applicant pool.

Design: Program-specific data from the Electronic Residency Application Service was collated for the 2018 medical student application cycle. Data were abstracted for all participating programs' applicants and those selected to interview. Applicants who did not enter a self-identified race/ethnicity were excluded from analysis. URM were defined as those identifying as Black/African American, Hispanic/Latino/of Spanish origin, American Indian/Alaskan Native, or Native Hawaiian/Pacific Islander-Samoan. Appropriate statistical analyses were accomplished.

Setting: Ten general surgery residency programs-5 independent programs and 5 university programs.

Participants: Residency applicants to the participating general surgery residency programs.

Results: Ten surgery residency programs received 10,312 applications from 3192 unique applicants. Seven hundred and seventy-eight applications did not include a self-identified race/ethnicity and were excluded from analysis. The racial/ethnic makeup of applicants in this study cohort was similar to that from 2017 to 2018 Electronic Residency Application Service data of 4262 total applicants to categorical general surgery. Programs received a median of 1085 (range: 485-1264) applications each and altogether selected 617 unique applicants for interviews. Overall, 2148 applicants graduated from US medical schools, and of those, 595 (28%) were offered interviews. The mean age of applicants was 28.8 ± 3.8 years and 1316 (41%) were female. Hispanic/Latino/of Spanish origin, Black, and American Indian/Alaskan Native/Hawaiian/Pacific Islander-Samoan applicants constituted 12%, 8%, and 1% of total applicants, but only 8%, 6%, and 1% of those selected for interview. Overall, 29% of applicants had United States Medical Licensing Examination (USMLE) Step 1 scores ≤220; 37 (6%) of those selected for interviews had a USMLE Step 1 score of ≤220. A higher proportion of URM applicants had USMLE scores ≤220 compared to White and Asian applicants. Non-white self-identification was a significant independent predictor of a lower likelihood of interview selection. Female gender, USMLE Step 1 score >220, and graduating from a US medical school were associated with an increased likelihood of being selected to interview.

Conclusions: URM applicants represented a disproportionately smaller percentage of applicants selected for interview. USMLE Step 1 scores were lower among the URM applicants. Training programs that use discreet USMLE cutoffs are likely excluding URM at a higher rate than their non-URM applicants. Attempts to recruit racially/ethnically diverse trainees should include program-level analysis to determine disparities and a focused strategy to interview applicants who might be overlooked by conventional screening tools.
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http://dx.doi.org/10.1016/j.jsurg.2019.05.018DOI Listing
December 2020

Phase 2 study of anastrozole in recurrent estrogen (ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial - ANZGOG 0903.

Gynecol Oncol 2019 07 23;154(1):29-37. Epub 2019 May 23.

Royal Hospital for Women, Prince of Wales Hospital and Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.

Background: The clinical benefit rate with aromatase inhibitors and the impact of treatment on quality of life (QOL) in endometrial cancer is unclear. We report the results of a phase 2 trial of anastrozole in endometrial cancer.

Methods: Investigator initiated single-arm, open label trial of anastrozole, 1 mg/d in patients with ER and/or PR positive hormonal therapy naive metastatic endometrial cancer. Patients were treated until progressive disease (PD) or unacceptable toxicity. The primary end-point was clinical benefit (response + stable disease) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life (QOL) and toxicity.

Results: Clinical benefit rate in 82 evaluable patients at 3 months was 44% (95% CI: 34-55%) with a best response by RECIST of partial response in 6 pts. (7%; 95% CI: 3-15%). The median PFS was 3.2 months (95% CI: 2.8-5.4). Median duration of clinical benefit was 5.6 months (95% CI: 3.0-13.7). Treatment was well tolerated. Patients who had clinical benefit at 3 months reported clinically significant improvements in several QOL domains compared to those with PD; this was evident by 2 months including improvements in: emotional functioning (39 vs 6%: p = 0.002), cognitive functioning (45 vs 19%: p = 0.021), fatigue (47 vs 19%: p = 0.015) and global health status (42 vs 9%: p = 0.003).

Conclusion: Although the objective response rate to anastrozole was relatively low, clinical benefit was observed in 44% of patients with ER/PR positive metastatic endometrial cancer and associated with an improvement in QOL.
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http://dx.doi.org/10.1016/j.ygyno.2019.05.007DOI Listing
July 2019