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Kevin Bray,1 Kaitlin Burge,1 Om Patel,1 Ishant Yadav,1 William Haynes,1 Nicholas Van Wagoner,2 Charles A Khoury3 1Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 2Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Kevin Bray, Email kevbray@uab.eduBackground: Beginning January 26th, 2022, the National Board of Medical Examiners transitioned scoring of the United States Medical Licensing Examination (USMLE) Step 1 from a 3-digit score to pass/fail. In the past, the Step 1 score has been weighted heavily by program directors (PDs) as one of the most important metrics when assessing medical student’s competitiveness.Objective: The objective of this study was to evaluate the perceptions of emergency medicine (EM) PDs on the transition to a pass/fail USMLE Step 1 exam, and to elicit the opinions of EM PDs on the USMLE examinations’ ability to predict resident performance.Methods: A survey consisting of ranking and multiple-choice questions was sent to EM PDs. The multiple-choice questions were asked to determine EM PDs level of confidence in the ability of Step 1 and Step 2 Clinical Knowledge (CK) to predict a student’s ability to succeed in residency. The ranking questions focused on assessing each program’s current resident selection practices in comparison to expected selection criteria changes following a transition to pass/fail Step 1. R studio and MATLAB were used for statistical analysis, and a P value < 0.05 was considered significant.Results: The survey was completed by 57 (20.21%) EM PDs. When asked if Step 1 and Step 2 CK are accurate predictors of a resident’s ability to perform clinically within EM, only 10.5% of PDs answered ‘yes’ to Step 1 being predictive, compared to 31.6% for Step 2 CK. Regarding selection criteria, the top quartile of attributes (standardized letters of evaluation [1st], away rotations [2nd], clerkship grades [3rd] and Step 2 CK score [4th]) remained the same following the transition.Conclusion: Our results indicate that the top quartile of attributes might remain the same, despite most PDs agreeing that Step 2 CK is a better predictor of a resident’s performance.Keywords: USMLE, NBME, Step 1, Step 2, emergency medicine, residency, program director, medical student

The recirculation zone created through vortex breakdown mechanisms in swirling flows plays a vital role for aerodynamic stabilization of turbulent flames in practical combustion systems. This zone interacts with the central recirculation zone (CRZ) of an upstream bluff body and this leads to a complex flow behavior that depends on the blockage ratio and swirl number. It has been previously observed that the vortex breakdown bubble (VBB) merges with the CRZ at large swirl number or blockage ratio. In this study, the influences of heat release on this flow structure and their physical mechanisms are explored through a series of large eddy simulations and experiments of bluff body stabilized premixed flames with swirling flows. Comparisons of simulation results with measurements are good. It is observed that in isothermal flows, as the swirl number or blockage ratio is increased, the vortex breakdown bubble moves upstream and its mean structure changes. The effect of heat release leads to considerable differences in the flow characteristics as the vortex breakdown bubble is pushed downstream due to dilatation. The critical swirl number, at which the VBB and CRZ merge, is observed to be higher in reacting flows for the same blockage ratio. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood's drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717-0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720-0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests' performance and evaluating its long-term impact on IBD management.

Background/objectives: Although there is a need for evidence-based physical activity programs in rural communities, evaluating such programs is often challenging due to access-related barriers and measurement tools that are not designed for rural contexts. This study aimed to explore and better understand the day-to-day experiences of rural-dwelling children using wrist-worn PA trackers as part of a study to develop a health promotion program., Methods: Ten caregivers and child dyads were enrolled ( n = 20). The children wore accelerometers pre- and post-intervention. Semi-structured interviews were completed post-intervention and were audio recorded, transcribed, and summary reports were generated based on recurring themes., Results: The children had a mean age of 8.7 (SD = 1.4) years and the majority were male (80%). The caregivers were female, white, and had a mean age of 43.6 (SD = 8.5) years, with an annual income of ≥USD 40,000. Factors contributing to device wear times included low caregiver burden, device functioning as a watch, and device interactivity. The children reported that the devices were acceptable, but may have changed their physical activity behaviors, with children regularly checking their step count. The caregivers preferred devices that monitored the children's activity levels without sharing location data., Conclusions: Identifying acceptable and feasible strategies to measure physical activity is vital to developing effective health promotion efforts. The lessons learned may help develop evaluation plans for implementing rural physical activity programming.

Objective: To identify differential trajectories of neurocognitive outcomes following pediatric concussion and investigate predictors associated with patterns of recovery up to 3 months., Methods: 74 participants aged 8-17 years completed attention/working memory, processing speed, and executive function measures at 2 weeks, 1 month, and 3 months post-injury. We used principal component analysis to generate a composite of information processing. Group-based trajectory modeling identified latent trajectories. Multinominal logistic regression was used to examine associations between risk factors and trajectory groups., Results: We identified three trajectories of neurocognitive outcomes. The medium (54.6%) and high improving groups (35.8%) showed ongoing increase in information processing, while the low persistent group showed limited change 3 months post-injury. This group recorded below average scores on Digit Span Forward and Backward at 3 months. History of pre-injury headache was significantly associated with the persistent low scoring group, relative to the medium improving ( p  = 0.03) but not the high improving group ( p  = 0.09)., Conclusions: This study indicates variability in neurocognitive outcomes according to three differential trajectories, with groups partially distinguished by preexisting child factors (history of frequent headaches). Modelling that accounts for heterogeneity in individual outcomes is essential to identify clinically meaningful indices that are indicative of children requiring intervention.

Background: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects., Methods/design: The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05., Discussion: This study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways., Trial Registration: ClinicalTrials.gov NCT06361381. Registered on 09 April 2024., (© 2024. The Author(s).)

Symptoms of hypocalcemia are reported in up to 50% of patients undergoing leukapheresis procedures. There is no set standard of practice for administering calcium supplementation in the prevention or treatment of hypocalcemia symptoms. The goal of this descriptive, retrospective study was to determine the prevalence of baseline hypocalcemia and symptomatic hypocalcemia during leukapheresis with acid citrate dextrose solution A and to identify patient characteristics associated with symptomatic hypocalcemia. Three percent of patients were found to have hypocalcemia before leukapheresis with 35% experiencing hypocalcemia symptoms during leukapheresis. Older age, higher albumin levels, and longer procedure time were associated with increased risk of hypocalcemia symptoms., (© 2023 Wiley Periodicals LLC.)

Background: Patients with rheumatoid arthritis (RA) have difficulties maintaining employment due to the impact of the disease on their work ability. This review aims to investigate the employment rates at different stages of disease and to identify predictors of employment among individuals with RA., Methods: The study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines focusing on studies reporting employment rate in adults with diagnosed RA. The literature review included cross-sectional and cohort studies published in the English language between January 1966 and January 2023 in the PubMed, Embase and Cochrane Library databases. Data encompassing employment rates, study demographics (age, gender, educational level), disease-related parameters (disease activity, disease duration, treatment), occupational factors, and comorbidities were extracted. Quality assessment was performed employing Newcastle-Ottawa Scale. Meta-analysis was conducted to ascertain predictors for employment with odds ratios and confidence intervals, and test for heterogeneity, using chi-square and I 2 -statistics were calculated. This review was registered with PROSPERO (CRD42020189057)., Results: Ninety-one studies, comprising of a total of 101,831 participants, were included in the analyses. The mean age of participants was 51 years and 75.9% were women. Disease duration varied between less than one year to more than 18 years on average. Employment rates were 78.8% (weighted mean, range 45.4-100) at disease onset; 47.0% (range 18.5-100) at study entry, and 40.0% (range 4-88.2) at follow-up. Employment rates showed limited variations across continents and over time. Predictors for sustained employment included younger age, male gender, higher education, low disease activity, shorter disease duration, absence of medical treatment, and the absence of comorbidities. Notably, only some of the studies in this review met the requirements for high quality studies. Both older and newer studies had methodological deficiencies in the study design, analysis, and results reporting., Conclusions: The findings in this review highlight the prevalence of low employment rates among patients with RA, which increases with prolonged disease duration and higher disease activity. A comprehensive approach combining clinical and social interventions is imperative, particularly in early stages of the disease, to facilitate sustained employment among this patient cohort., (© 2023. The Author(s).)

Objective: To evaluate changes in toothbrushing behaviour and plaque removal performance with usage of a next generation oscillating-rotating electric toothbrush (NG-OR)., Methods: This exploratory clinical study had a two-treatment, three-period, single-group, sequential design. Generally healthy adults with a screening whole mouth mean Turesky modified Quigley-Hein Plaque Index (TQHPI) score of at least 1.75 on a 0-5 scale and who were primarily OR brush users were enrolled. Participants used each OR toothbrush in A-B-B order, where a currently marketed OR brush with a traditional mechanical drive system (T-OR) was used in period A, and the NG-OR brush with a linear magnetic drive was used in period B. At Visit 1, qualifying participants brushed on-site with T-OR. After a 48 h washout, participants returned for Visit 2 and brushed on-site with NG-OR. Participants then used NG-OR for 1 week, twice daily, at home and returned for Visit 3 to brush on-site with NG-OR again. For all on-site brushings, participants were instructed to brush for 2 min without interactive features. Each toothbrush was tagged with a transmitter chip connected to a Motion Tracking System to record movements of the toothbrush and participant using infrared light transmission to determine Isochronicity (brushing time uniformly distributed across the dentition). Plaque was measured using TQHPI. Primary variables were Isochronicity and TQHPl whole mouth mean plaque reduction (pre-brushing minus post-brushing)., Results: Overall, 41 participants enrolled and received treatment; 40 completed the trial. NG-OR showed significantly greater Isochronicity after a single brushing (p = 0.043) and after a 1-week at-home use (p = 0.001) versus T-OR. NG-OR showed 41% greater whole mouth plaque removal than T-OR (p < 0.001) after a single brushing. Plaque reduction by region/surface was consistent with whole mouth results., Conclusion: The NG-OR brush showed greater brushing uniformity and plaque removal versus the T-OR brush., (© 2023 Procter & Gamble. International Journal of Dental Hygiene published by John Wiley & Sons Ltd.)

Introduction: Previous studies have shown that the population attributable risk of low forced expiratory volume in one second (FEV 1 ) for coronary artery disease (CAD) is substantial. FEV 1 can be low either because of airflow obstruction or ventilatory restriction. It is not known if low FEV 1 arising from spirometric obstruction or restriction are differently associated with CAD., Methods: We analyzed high resolution computed tomography (CT) scans acquired at full inspiration in lifetime non-smoker adults with no lung disease (controls) and those with chronic obstructive pulmonary disease enrolled in the Genetic Epidemiology of COPD (COPDGene) study. We also analyzed CT scans of adults with idiopathic pulmonary fibrosis (IPF) from a cohort of patients attending a quaternary referral clinic. Participants with IPF were matched 1:1 by FEV 1 %predicted to adults with COPD and 1:1 by age to lifetime non-smokers. Coronary artery calcium (CAC), a surrogate for CAD, was measured by visual quantification on CT using the Weston score. Significant CAC was defined as Weston score ≥7. Multivariable regression models were used to test the association of the presence of COPD or IPF with CAC, with adjustment for age, sex, body-mass-index, smoking status, hypertension, diabetes mellitus, and hyperlipidemia., Results: We included 732 subjects in the study; 244 with IPF, 244 with COPD, and 244 lifetime non-smokers. The mean (SD) age was 72.6 (8.1), 62.6 (7.4), and 67.3 (6.6) years, and median (IQR) CAC was 6 (6), 2 (6), and 1 (4), in IPF, COPD, and non-smokers, respectively. On multivariable analyses, the presence of COPD was associated with higher CAC compared to non-smokers (adjusted regression coefficient, β = 1.10 ± SE0.51; P = 0.031). The presence of IPF was also associated with higher CAC compared to non-smokers (β = 03.43 ± SE0.41; P < 0.001). The adjusted odds ratio for having significant CAC was 1.3, 95% CI 0.6 to 2.8; P = 0.53 in COPD and 5.6, 95% CI 2.9 to 10.9; P < 0.001 in IPF, compared to non-smokers. In sex stratified analyses, these associations were mainly noted in women., Conclusion: Adults with IPF displayed higher coronary artery calcium than those with COPD after accounting for age and lung function impairment., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The negative impact of adverse experiences in childhood on neurodevelopment is well documented. Less attention however has been given to the impact of variations in "normative" parenting behaviors. The influence of these parenting behaviors is likely to be marked during periods of rapid brain reorganization, such as late childhood. The aim of the current study was to investigate associations between normative parenting behaviors and the development of structural brain networks across late childhood. Data were collected from a longitudinal sample of 114 mother-child dyads (54% female children, M age 8.41 years, SD = 0.32 years), recruited from low socioeconomic areas of Melbourne, Australia. At the first assessment parenting behaviors were coded from two lab-based interaction tasks and structural magnetic resonance imaging (MRI) scans of the children were performed. At the second assessment, approximately 18 months later ( M age 9.97 years, SD = 0.37 years) MRI scans were repeated. Cortical thickness (CT) was extracted from T1-weighted images using FreeSurfer. Structural covariance (SC) networks were constructed from partial correlations of CT estimates between brain regions and estimates of network efficiency and modularity were obtained for each time point. The change in these network measures, from Time 1 to Time 2, was also calculated. At Time 2, less positive maternal affective behavior was associated with higher modularity (more segregated networks), while negative maternal affective behavior was not related. No support was found for an association between local or global efficacy and maternal affective behaviors at Time 2. Similarly, no support was demonstrated for associations between maternal affective behaviors and change in network efficiency and modularity, from Time 1 to Time 2. These results indicate that normative variations in parenting may influence the development of structural brain networks in late childhood and extend current knowledge about environmental influences on structural connectivity in a developmental context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Richmond, Beare, Johnson, Bray, Pozzi, Allen, Seal and Whittle.)

Objectives: Autologous chimeric antigen receptor (CAR) αβ T-cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. γδ T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T-cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood-derived CAR + Vδ1 γδ T cells expressing a second-generation CAR targeting the B-cell-restricted CD20 antigen., Methods: Donor-derived Vδ1 γδ T cells from peripheral blood were ex vivo -activated, expanded and engineered to express a novel anti-CD20 CAR. In vitro and in vivo assays were used to evaluate CAR-dependent and CAR-independent antitumor activities of CD20 CAR + Vδ1 γδ T cells against B-cell tumors., Results: Anti-CD20 CAR + Vδ1 γδ T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B-cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR + Vδ1 γδ T cells did not induce xenogeneic graft-versus-host disease in immunodeficient mice., Conclusion: These preclinical data support the clinical evaluation of ADI-001, an allogeneic CD20 CAR + Vδ1 γδ T cell, and a phase 1 study has been initiated in patients with B-cell malignancies (NCT04735471)., Competing Interests: KPN, TB, AA, AM, JMR, LB, MMB, JK‐W, HS, SP, AD, CM, NTH, HT, VDR, AG‐R, M Hoopes, DS, RS, M Herrman, SEA, BTA, ZA, SP and SMH are, or were, employees of Adicet Bio, Inc., and FD, KS and KB are employees of Regeneron Pharmaceuticals, Inc., (© 2022 Adicet Bio Inc. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)