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Objectives Extracorporeal membrane oxygenation (ECMO) is used to support patients in severe cardiogenic shock. In the absence of recovery, these patients may need to be listed for heart transplant (HT), which offers the best long-term prognosis. However, posttransplantation mortality is significantly elevated in patients who receive ECMO. The objective of the present study was to describe and risk-stratify different profiles of patients listed for HT supported by ECMO. Methods Patients listed for HT in the United Network for Organ Sharing database were analyzed. The primary outcome was 1-year survival and was assessed in patients bridged to transplant with ECMO (ECMOBTT) and patients who were previously supported on ECMO but had it removed before HT (ECMOREMOVED). Results Among 65,636 adult candidates listed for HT (between 2001 and 2017), 712 were supported on ECMO, 292 of whom (41%) underwent HT (ECMOBTT, n = 202; ECMOREMOVED, n = 90). Most of the patients with ECMOREMOVED were transplanted with a ventricular assist device. In ECMOBTT, recipient age (each 10-year increase), time on the waitlist (both defined as minor risk factors), need for dialysis, and need for mechanical ventilation (both defined as major risk factors) were independent predictors of mortality. ECMOREMOVED and ECMOBTT with no risk factors showed 1-year survival comparable to that in patients who were never supported on ECMO. Compared with patients who were never on ECMO, patients in ECMOBTT group with minor risk factors, 1 major risk factor, and 2 major risk factors had ~2-, ~5-, and >10-fold greater 1-year mortality, respectively (P Conclusions The HT recipients in the ECMOREMOVED and ECMOBTT groups with no risk factors showed similar survival as the HT recipients who were never supported on ECMO. In the ECMOBTT group, posttransplantation mortality increased significantly with increasing risk factors.

Background Individuals with autism spectrum disorder (ASD) exhibit frequent behavioral deficits in facial emotion recognition (FER). It remains unknown whether these deficits arise because facial emotion information is not encoded in their neural signal or because it is encodes but fails to translate to FER behavior (deployment). This distinction has functional implications, including constraining when differences in social information processing occur in ASD, and guiding interventions (i.e., developing prosthetic FER vs. reinforcing existing skills). Methods We utilized a discriminative and contemporary machine learning approach—deep convolutional neural networks—to classify facial emotions viewed by individuals with and without ASD (N = 88) from concurrently recorded electroencephalography signals. Results The convolutional neural network classified facial emotions with high accuracy for both ASD and non-ASD groups, even though individuals with ASD performed more poorly on the concurrent FER task. In fact, convolutional neural network accuracy was greater in the ASD group and was not related to behavioral performance. This pattern of results replicated across three independent participant samples. Moreover, feature importance analyses suggested that a late temporal window of neural activity (1000–1500 ms) may be uniquely important in facial emotion classification for individuals with ASD. Conclusions Our results reveal for the first time that facial emotion information is encoded in the neural signal of individuals with (and without) ASD. Thus, observed difficulties in behavioral FER associated with ASD likely arise from difficulties in decoding or deployment of facial emotion information within the neural signal. Interventions should focus on capitalizing on this intact encoding rather than promoting compensation or FER prostheses.

Background & Aims Coronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada. Methods We used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April–September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts. Results We identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P Conclusions Before and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

Rationale and Objectives Although metrics-based systems may incentivize academic output, no prior studies have evaluated the impact on publication metrics in academic radiology. This study presents a metrics-based system of awarding research protected time, and retrospectively evaluates its 9-year impact on publication productivity and impact factor. Materials and Methods Based on a metrics-based algorithm to award department funded Research Protected Time (RPT), metrics pre-RPT (2003–2009) and during the RPT period (2010–2018) from an academic radiology department were retrospectively analyzed to test the hypothesis that the RPT program resulted in higher publication productivity and journal impact factor at the departmental level and for faculty members receiving the award. Comparison was made between (1) pre-RPT and RPT periods and (2) during the RPT period, between RPT and non-RPT faculty members, for annual publication productivity normalized to faculty count (Student's t test) and median impact factor (Wilcoxon rank sum test). Results For the evaluation period of 2003–2018, 724 unique publications were identified: 15% (107/724) pre-RPT period and 85% (617/724) RPT period. Normalized annual publication productivity was higher during the RPT period compared to the Pre-RPT period (1.2 vs. 0.3, p = 0.002), and within the RPT period, higher among faculty who received RPT vs. non-RPT faculty (3.5 vs. 0.4, p = 0.002). Median impact factor was higher during the RPT period compared to pre-RPT period (2.843 vs. 2.322, p = 0.044), and within the RPT period, higher in RPT vs. non-RPT faculty (3.016 vs. 2.346, p Conclusion The implementation of a metrics-based system of funded, research protected time, was associated with increased publication productivity and increased impact factor.

Purpose: To examine the influence of occupational socialization on the beliefs and actions of six sport pedagogy doctoral students (DSs) in terms of physical education (PE) teaching and physical education teacher education (PETE). Method: Data were collected with five qualitative techniques and analyzed by employing analytic induction and constant comparison. Results: DSs had conservative or liberal views about PE and endorsed hybrid forms of PETE, which included elements of the behavioristic, traditional/craft, and critical inquiry orientations. Patterns of socialization that shaped these beliefs and actions were both congruent and contrasting with those described in past research. Conclusions: The study highlights the importance of asking potential DSs about their beliefs and the forces that shaped those beliefs during recruitment. In addition, it indicates that the potency of doctoral education can be enhanced when it has a dual focus on PETE and research and when DSs experience it within a cohort.

Background: The incidence of hypertensive disorders of pregnancy (HDP) are on the rise in the United States, especially in the South, which has a heavy chronic disease burden and large number of Medicaid nonexpansion states. Sizeable disparities in HDP outcomes exist by race/ethnicity, geography, and health insurance coverage. Our objective is to explore HDP in the Alabama Medicaid maternity population, and the association of maternal sociodemographic, clinical, and care utilization characteristics with HDP diagnosis. Materials and Methods: Data were from Alabama Medicaid delivery claims in 2017. Bivariate analyses were used to examine maternal characteristics by HDP diagnosis. Hierarchical generalized linear models, with observations nested at the county level, were used to assess multivariable relationships between maternal characteristics and HDP diagnosis. Results: Among women with HDP diagnosis, a higher proportion were older, Black, had other comorbidities, and had more perinatal hospitalizations or emergency visits compared with those without HDP diagnosis. There were increased odds of an HDP diagnosis for older women and those with comorbidities. Black women (adjusted odds ratio [aOR] = 1.24, 95% confidence interval [CI]: 1.16–1.33), women insured only during pregnancy by Sixth Omnibus Reconciliation Act Medicaid (aOR = 1.08, 95% CI: 1.02–1.15), and women entering prenatal care (PNC) in the second trimester (aOR = 1.10, 95% CI: 1.03–1.18) had elevated odds of HDP diagnosis compared with their counterparts. Conclusions: Beyond traditional demographic and clinical risk factors, not having preconception insurance coverage or first trimester PNC entry were associated with higher odds of HDP diagnosis. Improving the provision and timing of maternity coverage among Medicaid recipients, particularly in nonexpansion states, may help identify and treat women at risk of HDP and associated adverse perinatal outcomes.

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Purpose: To determine the influence of an elementary methods course and early field experience on eight preservice teachers’ (PTs’) value orientations. Method: The theoretical perspective employed was occupational socialization. Data were collected with the short form of the value orientation inventory and five qualitative techniques (formal and informal interviews, nonparticipant observation, critical incidents, and stimulated recall). The value orientation inventory profiles for the instructor and PTs were visually inspected for similarities and changes. Analytic induction and constant comparison were employed to analyze the qualitative data. Results: Value orientations of PTs with teaching and moderate coaching orientations were influenced by the methods course and early field experience, while those of PTs with strong coaching orientations were not. Factors leading to this evolution were the curriculum model employed, the instructor, and PTs’ increased confidence and knowledge of students. Summary and Conclusions: The study highlights the importance of faculty facilitating reflection on connections between instructional models and value orientations and how these relate to PTs’ beliefs.

Objective The aim of the study was to investigate the effectiveness of user testing for improving healthcare professionals' retrieval and comprehension of information in medicines guidelines. Methods The United Kingdom's Injectable Medicines Guide was selected as a case study. This gives guidance to nurses on preparing and administering intravenous medicines on hospital wards, in line with standard UK practice. Three rounds of user testing were completed with 10 hospital nurses per round, using the Injectable Medicines Guide for voriconazole and aminophylline. Participants used the guidelines to answer 17 questions related to the administration of these medicines. Answers were scored for "finding" and "understanding" the required information. Semistructured interviews explored participants' opinions of guideline content, design, and wording, with responses analyzed thematically. The guidelines were revised between rounds. Results In round 1, 8 of 17 questions were answered correctly by all participants. Participants had difficulty with dose, dilution, administration rate, and adverse effects questions. Revisions included new subsections and increased calculation support. In round 2, 14 of 17 questions were answered correctly by all participants. Difficulty persisted with dose and administration rate questions and further revisions made. In round 3, 15 of 17 questions were answered correctly by all participants. Across all rounds, participants considered appropriate subheadings and information order as important for fast location of information. Specific, detailed, and practical instructions were perceived as important to improve understandability and usefulness. Conclusions Key information in medicines guidelines may not be found and/or understood by healthcare professionals. User testing increased information retrieval and comprehension and could have an important role in improving the safety of medicines use.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (similar to 22x) and seven to similar to 1x coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence., Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe; 1332

Venturia effusa (syn. Fusicladium effusum), causal agent of pecan scab, is the most prevalent pathogen of pecan (Carya illinoinensis), causing severe yield losses in the southeastern United States. V. effusa is currently known only by its asexual (conidial) stage. However, the degree and distribution of genetic diversity observed within and among populations of V. effusa are typical of a sexually reproducing fungal pathogen, and comparable with other dothideomycetes with a known sexual stage, including the closely related apple scab pathogen, V. inaequalis. Using the mating type (MAT) idiomorphs from V. inaequalis, we identified a single MAT gene, MAT1-1-1, in a draft genome of V. effusa. The MAT1-1-1 locus is flanked by two conserved genes encoding a DNA lyase (APN2) and a hypothetical protein. The MAT locus spanning the flanking genes was amplified and sequenced from a subset of 14 isolates, of which 7 contained MAT1-1-1 and the remaining samples contained MAT1-2-1. A multiplex polymerase chain reaction screen was developed to amplify MAT1-1-1, MAT1-2-1, and a conserved reference gene encoding β-tubulin, and used to screen 784 monoconidial isolates of V. effusa collected from 11 populations of pecan across the southeastern United States. A hierarchical sampling protocol representing region, orchard, and tree allowed for analysis of MAT structure at different spatial scales. Analysis of this collection revealed the frequency of the MAT idiomorphs is in a 1:1 equilibrium of MAT1-1:MAT1-2. The apparent equilibrium of the MAT idiomorphs provides impetus for a renewed effort to search for the sexual stage of V. effusa. [Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Prostate-specific antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer; however, the significance of PSA at or near the time of death is not well understood. This study aimed to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC).The Mount Sinai Genitourinary Cancer Biorepository, an institutional review board-approved, single-institution database containing all consented genitourinary cancer patients seen between 2010 and 2018, was used to identify and stratify patients into the following cohorts based on their PSA at or near death:100 ng/mL, 100-1000 ng/mL, and1000 ng/mL. Analyses were performed to assess clinical characteristics of disease, treatment response, and outcomes.We identified 1097 patients with prostate cancer, and 101 were confirmed to be deceased following a diagnosis of mCRPC. In patients with mCRPC, cohorts of higher PSA level at death were associated with lower Gleason score at diagnosis and a trend toward longer time to mCRPC and longer time from diagnosis to death, despite a higher burden of disease at death. Conversely, subgroup analysis of PSA10 ng/mL at death was associated with lower rates of imaging within 6 months of death, lower treatment rate, and worse clinical outcomes.Cohorts of different PSA levels at death in mCRPC patients showed distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Imaging for the patient population with very low PSA levels may be underutilized and should be considered more routinely.

Mental toughness has been associated with factors related to psychological well-being, but little is known about its relationship with stigma toward mental health and mental health help-seeking. This study investigated the relationship between mental toughness, sport-related well-being, and personal stigma toward mental health in a sample of 154 National Collegiate Athletic Association Division I student-athletes. The moderating effect of mental toughness on the relationship between public stigma and self-stigma toward mental health help-seeking was also explored. Mental toughness was significantly and positively associated with sport-related well-being, but not significantly related to personal stigma toward mental health. Moderation analysis indicated that mental toughness was not a significant moderator of the relationship between public stigma and self-stigma, but higher levels of mental toughness were significantly associated with lower levels of stigma toward mental health help-seeking. Building mental toughness may be a way to increase well-being and to reduce stigma toward help-seeking in student-athletes.

Background Antidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP. Methods We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0–100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason. Results We included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI − 6.15 to − 2.50) on a 0–100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo. Conclusions Treatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP. Trial registration We prospectively registered the protocol for this systematic review on PROSPERO (CRD42020149275).

Given the importance of the period of life from 10 to 30 years in terms of cognitive development and education, combined with the high incidence of traumatic brain injury (TBI) during this period, and limited consensus as to the pattern and degree of cognitive impairment post TBI during this period, we conducted a systematic review to investigate cognitive performance across a range of domains among individuals between the ages of 10 and 30 years who had sustained a TBI. We searched five databases and identified 799 unique records; 52 met our inclusion criteria. These studies reported cognitive function for intelligence, attention, memory, processing speed, and executive function. The majority of the studies reported significant effects, suggesting that TBI is associated with cognitive impairments in these domains. Nine of the studies used physiological tests (EEG and fMRI), the outcomes of which supported behaviorally demonstrated cognitive deficits. In the studies we reviewed, individuals aged 10-30 years who had experienced a TBI performed worse than healthy controls on cognitive function measures - specifically for attention, memory, processing speed, and executive function. In the studies that subjected the individuals with TBI to EEG and fMRI, atypical activation in associated brain regions was demonstrated while the individuals were undergoing cognitive tasks. However, caution should be taken when interpreting the overall results due to the high risk of bias across the majority of the studies. The broader implications of reduced cognitive performance after TBI across this age range are yet to be fully understood. Refereed/Peer-reviewed

Background Perforated peptic ulcer is a morbid emergency general surgery condition. Best practices for postoperative care remain undefined. Surgical dogma preaches practices such as peritoneal drain placement, prolonged nil per os, and routine postoperative enteral contrast imaging despite a lack of evidence. We aimed to evaluate the role of postoperative enteral contrast imaging in postoperative perforated peptic ulcer care. Our primary objective was to assess effects of routine postoperative enteral contrast imaging on early detection of clinically significant leaks. Methods We conducted a multicenter retrospective cohort study of patients who underwent repair of perforated peptic ulcer between July 2016 and June 2018. We compared outcomes between those who underwent routine postoperative enteral contrast imaging and those who did not. Results Our analysis included 95 patients who underwent primary/omental patch repair. The mean age was 60 years, and 54% were male. Thirteen (14%) had a leak. Eighty percent of patients had a drain placed. Nine patients had leaks diagnosed based on bilious drain output without routine postoperative enteral contrast imaging. Use of routine postoperative enteral contrast imaging varied significantly between institutions (30%–87%). Two late leaks after initial normal postoperative enteral contrast imaging were confirmed by imaging after a clinical change triggered the second study. Two patients had contained leaks identified by routine postoperative enteral contrast imaging but remained clinically well. Duration of hospital stay was longer in those who received routine postoperative enteral contrast imaging (12 vs 6 days, median; P = .000). Conclusion Routine postoperative enteral contrast imaging after perforated peptic ulcer repair likely does not improve the detection of clinically significant leaks and is associated with increased duration of hospital stay.

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Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

Purpose: To determine the impact of two preservice teachers’ value orientations on their interpretation and delivery of the skill themes approach. Method: The short form of the value orientations inventory and five qualitative techniques were used to collect data. Participants’ value orientations inventory profiles were illustrated graphically. Interpretive data were analyzed using analytic induction and constant comparison. Findings: Results from the short form of the value orientations inventory indicated that Meagan prioritized social responsibility, learning process, and disciplinary mastery, while Jared favored social responsibility, self-actualization, and ecological integration. Qualitative data largely supported these value orientation profiles and indicated that the preservice teachers’ approaches to teaching skill themes differed and were influenced by their pedagogical beliefs. Moreover, qualitative data illustrated how Meagan’s and Jared’s value orientations and interpretations of the skill themes approach had changed and developed. Conclusions: These findings emphasize the importance of preservice teachers engaging in philosophical reflection on the connections between their beliefs and their interpretations of curriculum models.

Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease.

Purpose: Unstable pelvic ring injuries produced by external rotation of the hemipelvis and a symphyseal disruption are most often treated with internal fixation of the anterior ring, with percutaneous treatment of the posterior ring as needed. In some clinical situations, patients are treated with external fixation for their anterior injuries and the long-term functional outcomes associated with external fixation are not well understood. We ask if there is a difference in functional outcome, between treatment of these injuries with internal versus external fixation, when measured at a minimum of three years after injury. Method: This was a retrospective cohort study performed at a level one regional trauma center. Trauma database review identified 128 patients, with 70 subsequently excluded, with unstable anterior posterior compression (APC) pelvic ring injuries (OTA 61B2.3 & 61C1.2) treated with surgery with minimum three years of follow-up. An intervention of internal fixation versus external fixation of anterior pelvic ring was performed, and depending on the injury, supplemented with posterior iliosacral screw fixation. Main outcome was measured with the Majeed functional outcome score (0-100). Results: Patients treated with external fixation reported a Majeed score of 70 (95% CI 28-100) compared to 79 (95% CI 36-100) in those with internal fixation (p-value 0.28). Subgroups of the Majeed score were not significantly different (p value > 0.05). Open fractures, severity of injury, and ISS were worse in those treated with external fixation. There was no differential loss to follow-up. Conclusion Patients with unstable pelvic ring injuries with symphyseal disruptions treated with external fixation as definitive treatment versus internal fixation may fare no different in the long term.

Background Familiarity among cardiac surgery team members may be an important contributor to better outcomes and thus serve as a target for enhancing outcomes. Methods Adult cardiac surgical procedures (n = 4,445) involving intraoperative providers were evaluated at a tertiary hospital between 2016 and 2020. Team familiarity (mean of prior cardiac surgeries performed by participating surgeon/nonsurgeon pairs within 2 years before the operation) were regressed on cardiopulmonary bypass duration (primary—an intraoperative measure of care efficiency) and postoperative complication outcomes (major morbidity, mortality), adjusting for provider experience, surgeon 2-year case volume before the surgery, case start time, weekday, and perioperative risk factors. The relationship between team familiarity and outcomes was assessed across predicted risk strata. Results Median (interquartile range) cardiopulmonary bypass duration was 132 (91–192) minutes, and 698 (15.7%) patients developed major postoperative morbidity. The relationship between team familiarity and cardiopulmonary bypass duration significantly differed across predicted risk strata (P = .0001). High (relative to low) team familiarity was associated with reduced cardiopulmonary bypass duration for medium-risk (–24 minutes) and high-risk (–27 minutes) patients. Increasing team familiarity was not significantly associated with the odds of major morbidity and mortality. Conclusion Team familiarity, which was predictive of improved intraoperative efficiency without compromising major postoperative outcomes, may serve as a novel quality improvement target in the setting of cardiac surgery.

Background Radium-223 is a bone-seeking, alpha-emitting radionuclide used in metastatic castration-resistant prostate cancer (mCRPC). Radium-223 increases the risk of fracture when used in combination with abiraterone and prednisolone. The risk of fracture in men receiving radium-223 monotherapy is unclear. Patients and Methods This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort (n = 36) matched for fracture risk and not treated with radium-223. Bone fractures were assessed using whole-body magnetic resonance imaging. The primary outcome was risk of new fractures. Results Thirty-six patients were treated with up to six 4-week cycles of radium-223. With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% confidence interval, 35.3-71.6) at 12 months. On multivariate analysis, prior corticosteroid use was associated with risk of fracture. In the reference cohort (n = 36), 16 new fractures were identified in 12 patients over a median follow-up of 24 months. Across both cohorts, 67% of all fractures occurred at uninvolved bone. Conclusions Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce the risk of fragility fractures., Micro-Abstract Radium-223 increases the risk of fracture in combination with abiraterone and prednisolone. The fracture risk of radium-223 monotherapy is unclear. This prospective study assessed fracture incidence in men treated with radium-223 matched with a cohort that did not have radium-223. We identified 74 new fractures in 20 patients receiving radium-223. Most fractures occurred in bones without apparent metastases. Bone health agents should be mandatory before starting radium-223.

Student-athletes are susceptible to mental health problems that disrupt optimal functioning and well-being. Despite having many protective factors, student-athletes represent an at-risk subgroup of college students who experience mental health concerns due to the distress of balancing multiple obligations. However, many student-athletes underutilize psychological services. Stigma is the main barrier preventing student-athletes from seeking help, and mental health literacy (MHL) interventions addressing knowledge and beliefs about mental disorders have traditionally been used to destigmatize mental illness. This study investigated the impact of a 4-week program on stigma, MHL, and attitudes and intentions toward seeking help with 33 National Collegiate Athletic Association Division I student-athletes. The program was composed of four science-based interventions—MHL, empathy, counter stereotyping, and contact—delivered face-to-face within a group setting. MHL, attitudes toward seeking help, and intentions to seek counseling improved from preintervention to postintervention and to 1-month follow-up. Self-stigma was reduced from preintervention to postintervention.

OBJECTIVE The diagnosis of single-suture craniosynostosis can be made by physical examination, but the use of confirmatory imaging is common practice. The authors sought to investigate preoperative imaging use and to describe intracranial findings in children with single-suture synostosis from a large, prospective multicenter cohort. METHODS In this study from the Synostosis Research Group, the study population included children with clinically diagnosed single-suture synostosis between March 1, 2017, and October 31, 2020, at 5 institutions. The primary analysis correlated the clinical diagnosis and imaging diagnosis; secondary outcomes included intracranial findings by pathological suture type. RESULTS A total of 403 children (67% male) were identified with single-suture synostosis. Sagittal (n = 267), metopic (n = 77), coronal (n = 52), and lambdoid (n = 7) synostoses were reported; the most common presentation was abnormal head shape (97%), followed by a palpable or visible ridge (37%). Preoperative cranial imaging was performed in 90% of children; findings on 97% of these imaging studies matched the initial clinical diagnosis. Thirty-one additional fused sutures were identified in 18 children (5%) that differed from the clinical diagnosis. The most commonly used imaging modality by far was CT (n = 360), followed by radiography (n = 9) and MRI (n = 7). Most preoperative imaging was ordered as part of a protocolized pathway (67%); some images were obtained as a result of a nondiagnostic clinical examination (5.2%). Of the 360 patients who had CT imaging, 150 underwent total cranial vault surgery and 210 underwent strip craniectomy. The imaging findings influenced the surgical treatment 0.95% of the time. Among the 24% of children with additional (nonsynostosis) abnormal findings on CT, only 3.5% required further monitoring. CONCLUSIONS The authors found that a clinical diagnosis of single-suture craniosynostosis and the findings on CT were the same with rare exceptions. CT imaging very rarely altered the surgical treatment of children with single-suture synostosis.

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p.(Asp248Glu)] in the highly-conserved motor domain of KIF1A. In addition, three individuals with severe neurodevelopmental disorder along with clinical features overlapping with KAND are also reported carrying de novo heterozygous novel [NP_001230937.1:p.(Cys92Arg) & p.(Pro305Leu)] or previously reported [NP_001230937.1:p.(Thr99Met)] variants in KIF1A. In silico tools predicted these variants to be likely pathogenic, and 3D molecular modelling predicted defective ATP hydrolysis and/or microtubule binding. Using the neurite tip accumulation assay, we demonstrated that all novel KIF1A variants significantly reduced the ability of the motor domain of KIF1A to accumulate along neurite lengths of differentiated SH-SY5Y cells. In vitro microtubule gliding assays showed significantly reduced velocities for the variant p.(Asp248Glu) and reduced microtubule binding for the p.(Cys92Arg) and p.(Pro305Leu) variants, suggesting decreased ability of KIF1A to move along microtubules. Thus, this study further expanded the phenotypic characteristics of KAND individuals with pathogenic variants in KIF1A motor domain to include clinical features commonly seen in RTT individuals. This article is protected by copyright. All rights reserved.

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes., Region‐wise effect sizes and reproducibility rates of hemispheric asymmetry effects. In general, effects with higher effect sizes showed higher reproducibility, given the same conditions (e.g., sample size and data heterogeneity).

There is an urgent need to better understand the micronutrient demands of pregnancy due to the complex physiological adaptations during the gestational period and the importance of micronutrients in maternal-fetal health. Rigorous studies of micronutrients in pregnancy are significantly lacking due to a number of issues including the exclusion of pregnant people in research, methodological barriers to studying micronutrients, and the multidisciplinary expertise required for such studies. Stable isotopes present a unique methodological opportunity to quantify pregnancy-related changes in the absorption, distribution, metabolism, and excretion of micronutrients. We demonstrate here through a rapid review of the published literature that this approach is dramatically underutilized outside of calcium. In this perspective, we discuss the use of stable isotopes to study micronutrient physiology and our experiences in addressing the need for more studies in this area. Finally, we discuss how we might overcome major barriers to move toward a better understanding of micronutrient physiology in pregnancy.

The infection of Pseudomonas syringae pv. actinidiae in kiwifruit is currently assessed by numerous methodologies, each with their own limitations. Most studies are based on either a laborious method of growth quantification of the pathogen or qualitative assessments by visual scoring following stem or cutting inoculation. Additionally, when assessing for resistance against specific pathogen effectors, confounding interactions between multiple genes in the pathogen can make mapping resistance phenotypes nearly impossible. Here, we present robust alternative methods to quantify pathogen load based on rapid bacterial DNA quantification by PCR, the use of Pseudomonas fluorescens, and a transient reporter eclipse assay for assessing resistance conferred by isolated bacterial avirulence genes. These assays compare well with bacterial plate counts to assess bacterial colonization as a result of plant resistance activation. The DNA-based quantification, when coupled with the P. fluorescens and reporter eclipse assays to independently identify bacterial avirulence genes, is rapid, highly reproducible, and scalable for high-throughput screens of multiple cultivars or genotypes. Application of these methodologies will allow rapid and high-throughput identification of resistant cultivars and the bacterial avirulence genes they recognize, facilitating resistance gene discovery for plant breeding programs.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Unrest in Chile over inequalities has underscored the need to improve public hospitals. Nursing has been overlooked as a solution to quality and access concerns, and nurse staffing is poor by international standards. Using Chile's new diagnosis-related groups system and surveys of nurses and patients, we provide information to policy makers on feasibility, net costs, and estimated improved outcomes associated with increasing nursing resources in public hospitals.For this multilevel cross-sectional study, we used data from surveys of hospital nurses to measure staffing and work environments in public and private Chilean adult high-complexity hospitals, which were linked with patient satisfaction survey and discharge data from the national diagnosis-related groups database for inpatients. All adult patients on medical and surgical units whose conditions permitted and who had been hospitalised for more than 48 h were invited to participate in the patient experience survey until 50 responses were obtained in each hospital. We estimated associations between nurse staffing and work environment quality with inpatient 30-day mortality, 30-day readmission, length of stay (LOS), patient experience, and care quality using multilevel random-effects logistic regression models and zero-truncated negative binomial regression models, with clustering of patients within hospitals.We collected and analysed surveys of 1652 hospital nurses from 40 hospitals (34 public and six private), satisfaction surveys of 2013 patients, and discharge data for 761 948 inpatients. Nurse staffing was significantly related to all outcomes, including mortality, after adjusting for patient characteristics, and the work environment was related to patient experience and nurses' quality assessments. Each patient added to nurses' workloads increased mortality (odds ratio 1·04, 95% CI 1·01-1·07, p0·01), readmissions (1·02, 1·01-1·03, p0·01), and LOS (incident rate ratio 1·04, 95% CI 1·01-1·06, p0·05). Nurse workloads across hospitals varied from six to 24 patients per nurse. Patients in hospitals with 18 patients per nurse, compared with those in hospitals with eight patients per nurse, had 41% higher odds of dying, 20% higher odds of being readmitted, 41% higher odds of staying longer, and 68% lower odds of rating their hospital highly. We estimated that savings from reduced readmissions and shorter stays would exceed the costs of adding nurses by US$1·2 million and $5·4 million if the additional nurses resulted in average workloads of 12 or ten patients per nurse, respectively.Improved hospital nurse staffing in Chile was associated with lower inpatient mortality, higher patient satisfaction, fewer readmissions, and shorter hospital stays, suggesting that greater investments in nurses could return higher quality of care and greater value.Sigma Theta Tau International, University of Pennsylvania Global Engagement Fund, University of Pennsylvania School of Nursing's Center for Health Outcomes, and Policy Research and Population Research Center.For the Spanish translation of the abstract see Supplementary Materials section.

Using optical tweezers, we investigate target search and cleavage by CRISPR–Cas12a on force-stretched λ-DNA. Cas12a uses fast, one-dimensional hopping to locate its target. Binding and cleavage occur rapidly and specifically at low forces (≤5 pN), with a 1.8 nm rate-limiting conformational change. Mechanical distortion slows diffusion, increases off-target binding but hinders cleavage., CRISPR-Cas12a target search and cleavage on force-stretched λ-DNA using optical tweezers.

Purpose of review Craniosynostosis, a condition of premature cranial suture fusion, can have significantly detrimental effects on development and growth due to sequelae of increased intracranial hypertension (ICP), exophthalmos, and upper airway obstruction. Evolving surgical treatments now include distraction osteogenesis (DO) due to its many benefits relative to standard cranial vault remodeling procedures. This article provides an overview and update of different surgical applications of DO for patients with craniosynostosis. Recent findings DO has been utilized successfully for single and multisuture craniosynostosis with or without midface hypoplasia to increase intracranial volume, decrease ICP and improve aesthetics. It has been applied in single suture synostosis, posterior vault DO, fronto-orbital advancement, monobloc DO and Le Fort III DO. DO has been applied through modification of traditional surgical procedures with success in maintaining goals of surgery while reducing risk. Summary DO is still a relatively new and evolving surgical technique for patients with syndromic and nonsyndromic craniosynostosis. With promising benefits, consideration for each procedure should be weighed until longer-term data is available.

Background: Expert guidelines recommend annual monitoring of 25-hydroxyvitamin D (25-OHD) and maintaining 25-OHD ≥30 ng/ml in patients with dystrophinopathies. Objective: We hypothesized that 25-OHD remains stable and requires less frequent monitoring in patients taking stable maintenance doses of vitamin D. Methods: We performed a retrospective cohort study, using the electronic health record to identify 26 patients with dystrophinopathies with a baseline 25-OHD ≥30 ng/mL and at least one additional 25-OHD measurement. These patients had received a stable dose of vitamin D for ≥3 months prior to their baseline 25-OHD measurement and throughout follow-up. The main outcome measured was the mean duration time the subjects spent with a 25-OHD ≥30 ng/mL. Results: Only 19% of patients dropped their 25-OHD to

Background Several studies have reported an association between inflammatory bowel disease (IBD) and Parkinson’s disease (PD). The aim of this study is to re-evaluate for an association between IBD and PD while controlling for potential socioeconomic and environmental confounders. Methods We performed a retrospective cohort study using the Truven Health Marketscan database between January 1, 2005, and December 31, 2014. Individuals with IBD and household age-matched controls were identified. Adjusted hazard ratios (HRs) were calculated for the development of incident PD, adjusting for age, sex, residence type, US region, comorbidities, and behavior. Results In all, 154 051 subjects with IBD and an equal number of controls were identified. During a mean (SD) follow-up of 3.8 (2.2) years, 132 incident PD cases were identified. There was no significant association between IBD and PD (adjusted HR, 1.01; 0.72–1.42) when adjusting for the confounders previously mentioned. Conclusions We found no statistically significant association between these disorders. It is possible that previous associations identified between these disorders were confounded by environmental and socioeconomic factors.

Background: The use of factor Xa inhibitors has grown in popularity; however, the risk of major bleeding events requires for the appropriate reversal agent. The recent approved agent for factor Xa inhibitor reversal, andexanet alfa, has limited clinical efficacy and safety data, and it can be a financial burden on healthcare systems due to its high cost. Four-factor prothrombin complex concentrate (4F-PCC) has been utilized off label in patients with factor Xa inhibitor-related bleedings. Objective: The aim of this study was to assess the safety and efficacy of 4F-PCC in managing factor Xa inhibitor-related bleedings. Methods: This is an observational, retrospective review of 4F-PCC usage in treating factor Xa inhibitor-related bleeds from May 2014 to December 2018 at a single health system. Efficacy was evaluated using the assessment criteria described by Sarode et al. Secondary outcomes analyzed included thromboembolic events, length of stay, mortality, and discharge disposition. Results: Fifty-nine patient charts were reviewed, and 48 patients were included in the study analysis. The administration of 4F-PCC achieved effective hemostasis in 33 patients (68%), and effective hemostasis was achieved in 12 patients (86%) who had intracranial hemorrhage and did not receive any surgical intervention. Thromboembolic events occurred in 4 patients within 30 days from 4F-PCC use. A majority of patients (85.4%) were discharged from the hospital to home or long-term care; 7 patients (14.6%) expired in the hospital. Conclusion: Efficacy was achieved in over half of the patient population in this cohort who received 4F-PCC for factor Xa inhibitor-related bleeding events.

BACKGROUND. Incidental homogeneous renal masses are frequently encountered at portal venous phase CT. The American College of Radiology Incidental Findings Committee's white paper on renal masses r...

We used male BTBR mice carrying the Lep(ob) mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lep(ob/ob) (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O(2) followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.

Background: dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non-small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. Patients and methods: aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR

Purpose Although peer review in radiation oncology (RO) has been recommended to improve quality of care, an analysis of modifications resulting from an RO multidisciplinary presimulation standardized review process has yet to be empirically demonstrated. Methods and Materials A standardized simulation directive was used for patients undergoing simulation for external beam radiation therapy at a single tertiary care institution. The simulation directives were presented, and all aspects were reviewed by representatives from key RO disciplines. Modifications to the original directives were prospectively captured in a quality improvement registry. Association between key variables and the incidence of modifications were performed using Fisher exact test and t test. Results A registry of 500 consecutive simulations for patients undergoing radiation therapy was reviewed. A median of 105 simulations occurred per month. All simulation directives were entered by a physician a median of 3 days before simulation (range, 1-76 days). The treatment intent was curative for 269 patients (53.8%), palliative for 203 patients (40.6%), and benign for 3 patients (0.6%). Twenty-five (5%) patients did not have a treatment intent selected. Based on RO multidisciplinary review, 105 directives (21%) were modified from the original intent, with 29 (5.8%) requiring more than 1 modification. A total of 149 modifications were made and categorized as changes to patient positioning and immobilization (n = 100, 20%), treatment site and care path (n = 34, 6.8%), simulation coordination activities (n = 6, 1.2%), and treatment technique and planning instructions (n = 9, 1.8%). A higher proportion of modifications occurred at the time of multidisciplinary review in patients receiving more complex treatments (intensity modulated radiation therapy/stereotactic radiosurgery/stereotactic body radiation therapy [IMRT/SRS/SBRT] vs 3-dimensional radiation therapy [3DCRT] radiation therapy, 25% vs 16%, P Conclusions Given the complexity of radiation therapy simulation, standardization of directives with prospective RO multidisciplinary presimulation peer review is critical to optimizing department processes and reducing errors. Approximately 1 in 5 patients benefits from this peer review process, especially patients treated with IMRT/SRS/SBRT.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The molecular characteristics of histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed total RNA sequencing with fresh frozen thyroid tissues from a cohort of three categories of samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex or the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 256 coding genes and 5 noncoding genes have been reported as cancer genes involved in cell proliferation, apoptosis, and/or tumorigenesis. Bioinformatics analysis with Ingenuity Pathway Analysis software revealed that “Cancer, Organismal Injury and Abnormalities, Cellular Response to Therapeutics, and Cellular Movement” were major dysregulated pathways in the NAT tissues. This study provides improved insight into the complexity of gene expression changes in the thyroid glands of patients with PTC.

Background Clinical decisions regarding the utility of carotid revascularization are informed by randomized controlled trial (RCT) results. However, RCTs generally require participating surgeons to meet strict inclusion criteria with respect to procedure volume. The purpose of this study was to compare annual surgeon volume for carotid endarterectomy (CEA) in contemporary practice to RCT inclusion thresholds. Methods Surgeon volume thresholds were identified in 17 RCTs evaluating the efficacy of CEA (1986-present, n = 17). Contemporary annual surgeon volumes (2012–2017) were identified by aggregating data from the Medicare Provider Utilization Database and Healthcare Cost and Utilization Project Network (HCUP), and compared to RCT inclusion thresholds. Further comparisons were performed over time, and across specialties (i.e., vascular surgeon vs. other, based on board certification associated with provider NPI). Results Minimal surgeon volume in 17 RCTs ranged from 10 to 25 CEA annually when specific case volumes were required. From 2012 to 2017, CEA incidence in Medicare beneficiaries declined from 68,608 to 56,004 and became increasingly consolidated in fewer providers (7,331 vs. 6,626). However, in 2016 only 26.2% of surgeons performing CEA in Medicare beneficiaries would have met the least stringent volume requirement (10 CEA/year). Only 6.5% of surgeons performing CEA met the most stringent RCT volume threshold (25 cases/year) during the same time period. In 2017, 819 vascular surgeons (25.5% of those certified in the specialty) performed >10 CEA in Medicare beneficiaries. Conclusions The majority of surgeons performing CEA do not meet the annual volume thresholds required for participation in the RCTs that have evaluated the efficacy of carotid revascularization. Given the established volume-outcome relationship in CEA, the disparity between surgeon experience in the context of RCTs versus contemporary practice is concerning. These findings have potential implications for informed decision-making, hospital privileging, and regionalization of care.

Purpose To test if the relative change in FDG-PET SUVmax over the course of treatment was associated with disease progression and overall survival. Additionally, the prognostic values of other first-order PET-metric changes were investigated. Methods The study included 38 patients with stage II–III NSCLC, who underwent concurrent chemoradiotherapy. Patients received two pre-treatment FDG-PET scans and four during-treatment scans at weekly intervals. SUVmax was normalized to the start of treatment and analyzed using linear regression. Linear regression coefficients of other first order PET-metrics were grouped according to dissimilarity. Associations to patient outcome were analyzed using Cox hazard ratio. Results Twenty-eight patients satisfied the criteria for analysis. All PET-metrics demonstrated a strong linear correlation with time during treatment [median R-range: −0.87: −0.97]. No strong associations (p > 0.10) were found for the relative slope of SUVmax to patient outcomes. Other first-order metrics did correlate with outcome but the single imaging time-point maximizing the association of PET response with outcome varied per PET metric and outcome parameter. Conclusion All investigated FDG PET metrics linearly decreased during treatment. Relative change in SUVmax was not associated to patient outcome while several other first order PET-metrics were related to patient outcome. A single optimal imaging time-point could not be identified.

Background: Hospice patients are frequently confronted with potentially infectious complications necessitating antibiotic consideration. Information regarding the appropriate use of antibiotics and their impact on symptom management in hospice patients are unknown. Objectives: This study aimed to evaluate and describe the use of an antibiotic initiation tool in patients admitted to outpatient hospice services. The primary outcome assessed the percentage of antibiotics that were appropriately initiated based on Loeb’s Minimum Criteria (LMC) for Antibiotic Initiation Tool. Secondary outcomes included the number of patients with documented symptom resolution following antibiotic completion, the number of antibiotic courses that were successfully completed, and treatment-related adverse events. Methods: This was a retrospective, multisite, descriptive analysis of hospice patients treated with antibiotics between April 2019 and September 2020. Results: Two hundred and thirty patients were assessed for inclusion, with 172 meeting eligibility criteria and receiving a total of 201 antibiotic courses. Based on LMC, 84 of the 201 (42%) antibiotics ordered were appropriate, with 60% of these LMC-approved courses resulting in symptom resolution. Out of 201 total courses, 99 (49%) resulted in symptom resolution. Overall, 160 (80%) antibiotic courses were successfully completed. Conclusion: In this study, antibiotic initiation in hospice patients frequently did not meet LMC. Less than half of the antibiotics prescribed led to symptom resolution despite antibiotic course completion in most patients. There is no consensus or guidelines directing appropriate antibiotic decision-making in hospice patients. The appropriate use of antibiotics in terminally ill patients warrants additional research.

The Bosniak classification of cystic renal masses version 2019 (v.2019) includes an expanded number of types of masses in class II; such masses are considered benign in clinical practice. Data supporting these additions have not been well-documented. We aim to determine the proportion of malignant or probably malignant renal masses among the types added to Bosniak v.2019 class II. Multiple databases were searched for studies evaluating the proportion of malignant or probably malignant renal masses among new Bosniak v.2019 class II types, four for CT and two for MRI. Risk of bias and applicability was assessed using the QUADAS-2 tool. Ten studies (2068 renal masses) met inclusion criteria. Among the four added class II types at CT, the proportion of malignancy among (1) ‘homogeneous hyperattenuating (≥ 70 HU) masses at unenhanced CT’ was 0% (0/32) in three studies; (2) ‘homogeneous masses − 9 to 20 HU at unenhanced CT’ was 0% (0/1454) in two studies, and (3) ‘homogeneous masses 21 to 30 HU at portal-venous phase CT’ was 0% (0/454) in four studies. Masses that are homogeneous, have low attenuation, and are too small to characterize on CT had no supportive evidence. Among the two added class II types at MRI, the proportion of malignancy among (1) ‘homogeneous masses markedly hyperintense at unenhanced T2-weighted MR imaging (similar to CSF) was 0% (0/72) in one study, and (2) ‘homogeneous masses markedly hyperintense at T1-weighted MR imaging (~ 2.5 × renal parenchyma signal intensity)’ was 0% (0/32) and 5% (2/37) in two studies. Nine studies were at risk of bias within at least one QUADAS-2 domain. The addition of six types of cystic renal masses to Class II in the Bosniak v.2019 proposal may be justified but based on limited evidence, with no evidence for ‘homogeneous low attenuation masses that are too small to characterize’ on CT, and thus considering them benign is in part based on expert opinion. Protocol Registration: PROSERO CRD42020196408

Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers† (1). In addition, 27% of parents of children aged

ObjectiveTo identify novel disease associated loci for amyotrophic lateral sclerosis (ALS), we used sequencing data and performed in vitro and in vivo experiments to demonstrate pathogenicity of mutations identified inTP73.MethodsWe analyzed exome sequences of 87 patients with sporadic ALS and 324 controls, with confirmatory sequencing in independent ALS cohorts of >2,800 patients. For the top hit,TP73, a regulator of apoptosis and differentiation and a binding partner and homolog of the tumor suppressor geneTP53, we assayed mutation effects using in vitro and in vivo experiments. C2C12 myoblast differentiation assays, characterization of myotube appearance, and immunoprecipitation of p53-p73 complexes were performed in vitro. In vivo, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 targeting of zebrafishtp73to assay motor neuron number and axon morphology.ResultsFour heterozygous rare, nonsynonymous mutations inTP73were identified in our sporadic ALS cohort. In independent ALS cohorts, we identified an additional 19 rare, deleterious variants inTP73. PatientTP73mutations caused abnormal differentiation and increased apoptosis in the myoblast differentiation assay, with abnormal myotube appearance. Immunoprecipitation of mutant ΔN-p73 demonstrated that patient mutations hinder the ability of ΔN-p73 to bind p53. CRISPR/Cas9 knockout oftp73in zebrafish led to impaired motor neuron development and abnormal axonal morphology, concordant with ALS pathology.ConclusionTogether, these results strongly suggest that variants inTP73correlate with risk for ALS and indicate a role for apoptosis in ALS disease pathology.

Background Vioptix is a near-infrared spectroscopy tissue oximetry technology that allows for noninvasive monitoring of flap perfusion. Despite the reported benefits of Vioptix, the cost-effectiveness of this flap monitoring technology has not been compared to clinical examination alone. Methods A cost-effectiveness model, from the patient perspective, was constructed with two treatment arms: clinical examination versus clinical examination combined with Vioptix for flap monitoring after autologous, free flap breast reconstruction. Costs, utilities, and other model inputs were identified from the literature. One-way and probabilistic sensitivity analyses were performed. Gamma distributions were created for cost variables, and beta distributions were created for probability variables. An incremental cost-effectiveness ratio under $50,000 per quality-adjusted life-year (QALY) was considered cost-effective. All analyses were performed using TreeAge Pro (Williamstown, Mass.). Results Mean cost of autologous free tissue transfer breast reconstruction with clinical examination-based flap monitoring was found to be $37,561 with an effectiveness of 0.79, whereas the mean cost of clinical examination with Vioptix for flap monitoring was $39,361 with effectiveness of 0.82. This yielded an incremental cost-effectiveness ratio of $60,507 for clinical examination combined with Vioptix for flap monitoring. One-way sensitivity analysis revealed that clinical examination with Vioptix became cost-effective when the cost of Vioptix was less than $1487. Probabilistic sensitivity analysis found that clinical examination was cost-effective in 86.5 percent of cases. Conclusion Although clinical examination combined with Vioptix is minimally more effective for flap monitoring after autologous, free flap breast reconstruction, clinical examination alone is the more cost-effective flap monitoring option.