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Importance: The feasibility of implementing genome sequencing as an adjunct to traditional newborn screening (NBS) in newborns of different racial and ethnic groups is not well understood., Objective: To report interim results of acceptability, feasibility, and outcomes of an ongoing genomic NBS study in a diverse population in New York City within the context of the New York State Department of Health Newborn Screening Program., Design, Setting, and Participants: The Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study was a multisite, single-group, prospective, observational investigation of supplemental newborn genome screening with a planned enrollment of 100 000 participants. Parent-reported race and ethnicity were recorded at the time of recruitment. Results of the first 4000 newborns enrolled in 6 New York City hospitals between September 2022 and July 2023 are reported here as part of a prespecified interim analysis., Exposure: Sequencing of 156 early-onset genetic conditions with established interventions selected by the investigators were screened in all participants and 99 neurodevelopmental disorders associated with seizures were optional., Main Outcomes and Measures: The primary outcome was screen-positive rate. Additional outcomes included enrollment rate and successful completion of sequencing., Results: Over 11 months, 5555 families were approached and 4000 (72.0%) consented to participate. Enrolled participants reflected a diverse group by parent-reported race (American Indian or Alaska Native, 0.5%; Asian, 16.5%; Black, 25.1%; Native Hawaiian or Other Pacific Islander, 0.1%; White, 44.7%; 2 or more races, 13.0%) and ethnicity (Hispanic, 44.0%; not Hispanic, 56.0%). The majority of families consented to screening of both groups of conditions (both groups, 90.6%; disorders with established interventions only, 9.4%). Testing was successfully completed for 99.6% of cases. The screen-positive rate was 3.7%, including treatable conditions that are not currently included in NBS., Conclusions and Relevance: These interim findings demonstrate the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in a population of different racial and ethnic groups. DNA sequencing offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots. Additional studies are required to understand if these findings are generalizable to populations of different racial and ethnic groups and whether introduction of sequencing leads to changes in management and improved health outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT05990179.

Instrumenting the six-minute walk test (6MWT) adds information about gait quality and insight into fall risk. Being physically active and preserving multi-directional stepping abilities are also important for fall risk reduction. This analysis investigated the relationship of gait quality during the 6MWT with physical functioning and physical activity. Twenty-one veterans (62.2 ± 6.4 years) completed the four square step test (FSST) multi-directional stepping assessment, a gait speed assessment, health questionnaires, and the accelerometer-instrumented 6MWT. An activity monitor worn at home captured free-living physical activity. Gait measures were not significantly different between minutes of the 6MWT. However, participants with greater increases in stride time (ρ = -0.594, p < 0.01) and stance time (ρ = -0.679, p < 0.01) during the 6MWT reported lower physical functioning. Neither physical activity nor sedentary time were related to 6MWT gait quality. Participants exploring a larger range in stride time variability (ρ = 0.614, p < 0.01) and stance time variability (ρ = 0.498, p < 0.05) during the 6MWT required more time to complete the FSST. Participants needing at least 15 s to complete the FSST meaningfully differed from those completing the FSST more quickly on all gait measures studied. Instrumenting the 6MWT helps detect ranges of gait performance and provides insight into functional limitations missed with uninstrumented administration. Established FSST cut points identify aging adults with poorer gait quality.

Introduction: Severe metabolic alkaloses are relatively rare but can carry a high mortality rate. Treatment involves supportive care and treatment of underlying causes., Case Report: A 55-year-old male dependent on a gastrojejunostomy tube presented to the emergency department for altered mental status. The patient had metabolic alkalosis, electrolyte abnormalities, and prolonged QT interval on electrocardiogram. Examination and history revealed that chronic drainage of gastric fluid via malfunctioning a gastrojejunostomy tube resulted in profound alkalosis. The patient recovered with supportive care, electrolyte repletion, and gastrojejunostomy tube replacement., Conclusion: This case highlights the importance of gastrointestinal acid-base pathophysiology., Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.

Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age-related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise-related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Competing Interests: Competing interests: None declared.

Although Sc doped AlN (ScAlN) has been used extensively in micro-electro-mechanical systems (MEMS) devices and more recently in optical devices, there have not been thorough studies of its intrinsic optical losses. Here we explore the optical losses of the Sc 0.30 Al 0.70 N waveguide system by observing racetrack resonator waveguide quality factors. Using a partial physical etch, we fabricate waveguides and extract propagation losses as low as 1.6 ± 0.3 dB/cm at wavelengths around 1550 nm, mostly dominated by intrinsic material absorption from the Sc 0.30 Al 0.70 N thin film layer. The highest quality factor of the resonators was greater than 87,000. The propagation loss value is lower than any value previously published and shows that this material can be broadly used in optical modulators without significant loss.

Objective: Programs for early detection of psychosis help identify individuals experiencing emerging psychosis and link them with appropriate services, thereby reducing the duration of untreated psychosis (DUP). The authors used the cascade-of-care framework to identify various care stages between screening and enrollment in coordinated specialty care (CSC) and to determine attrition at each stage, with the goal of identifying points in the referral process that may affect DUP., Methods: Project partners included a college counseling center and CSC program. All college students seeking mental health services at a counseling center between 2020 and 2022 (N=1,945) completed the Prodromal Questionnaire-Brief (PQ-B) at intake. Students who met the distress cutoff score were referred for a phone screening. Those who met criteria on the basis of this screening were referred for assessment and possible enrollment into CSC., Results: Six stages in the cascade of care for early detection were identified. Of the students who completed the PQ-B as part of intake (stage 1), 547 (28%) met the PQ-B cutoff score (stage 2). Counselors referred 428 (78%) students who met the PQ-B cutoff score (stage 3), and 212 (50%) of these students completed the phone screening (stage 4). Seventy-two (34%) students completed a CSC eligibility assessment (stage 5), 21 (29%) of whom were enrolled in CSC (stage 6)., Conclusions: The cascade-of-care framework helped conceptualize the flow within a program for early psychosis detection in order to identify stages that may contribute to lengthier DUP. Future research is warranted to better understand the factors that contribute to DUP at these stages., Competing Interests: Dr. Tohen reports receiving honoraria for consultation for AbbVie, Alkermes, Intercellular Therapies, Johnson & Johnson, Lundbeck, Merck, Otsuka, and Roche. Dr. Bustillo reports receiving book royalties from UpToDate. The other authors report no financial relationships with commercial interests.

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active D -glucose into healthy mice. The observed real-time responses to laser-induced disruption include rapid serum extravasation, platelet aggregation, and neutrophil recruitment. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, and by a nitric oxide donor. As a control, vessel thrombo-inflammation is significantly reduced in mice injected with metabolically inert L -glucose. Venules in mice with diabetes show a similar response to laser-induced disruption and damage is reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies between transient metabolic and physical vascular perturbations and can reveal new aspects of brain pathophysiology., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The resonant interaction of a dielectric-coated conductive rod with the X-band microwave field is investigated. The magnetic field distribution of the Goubau standing radial surface waves was experimentally visualized by using a thermo-elastic optical indicator microscope, and the corresponding electric field distribution was determined via numerical simulations. These field distributions are characterized by a certain pattern of antinodes distinctive for standing waves. An analysis of these field distributions allows one to couple a coated rod with a cut Goubau line. A rod placed in the gap region perpendicular to the Goubau line results in a sharp rejection band in the transmission spectrum which is extremely sensitive to the changes in the surrounding media. The shifting rate of the resonance as a function of the dielectric shell thickness is approximately 1.4 GHz/mm. The Q -factor of copper rods depends on their size and dielectric shell thickness. Longer rods with more energy localization areas have higher Q -factors, typically 1.7 times higher (12.7 vs. 7.5). Moreover, incorporating a dielectric shell enhances energy confinement and can elevate the Q -factor by as much as 22 %. When a 25 mm Cu rod is situated inside a cut Goubau line system, the Q -factor values are significantly higher, with a ratio of 275 to 13. With the addition of a dielectric shell, the Q -factor can be elevated by 58 %. The versatility of the proposed controllable system makes it possible to tune the operating spectrum towards higher GHz and THz frequencies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study examines the development of children's self-assessment of their prosociality in normative social comparisons with an average peer, who was either a concrete individual, or an abstract one, at a school of average socioeconomic level in south Israel (N = 148, Age 6-12 years, 51% females; June 2021). Results show that older children exhibited the better-than-average (BTA) effect by perceiving themselves as more generous than their average peer. Conversely, younger children exhibited a worse-than-average effect, in that they assumed that their peers would act more generously than themselves ( η p 2 = .23 ). Only the older children (aged 8 years onward) were significantly affected by the concreteness of the target of comparison by exhibiting the BTA effect only when the average peer was abstract (not concrete)., (© 2023 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Aim: This exploratory study aimed to examine differences in rates of self and clinician-reports of trauma in youth at clinical high risk for psychosis (CHR) and whether rates of reporting differed by ethnicity., Methods: Self-reported history of trauma was collected at intake amongst youth at CHR enrolled in Coordinated Specialty Care (CSC) services (N = 52). A structured chart review was conducted for the same sample to identify clinician-reported history of trauma throughout treatment in CSC., Results: For all patients, frequency of self-reported trauma at intake to CSC (56%) was lower compared to clinician-reports of trauma throughout treatment (85%). Hispanic patients self-reported trauma at intake (35%) less frequently than non-Hispanics (69%) (p = .02). No differences were found in clinician reported exposure to trauma by ethnicity throughout treatment., Conclusion: Whilst further research is needed, these findings suggest the need for formalised, repeated, and culturally appropriate assessments of trauma within CSC., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

This Article examines how the rapid deregulation and rampant possession of firearms is likely going to impact policing, and the constitutional law that governs it. For the longest time, lawful gun carry, concealed or open, was exceedingly rare. For a police officer to see a gun was both to see danger, and a crime in progress. This link among guns, danger, and unlawful possession has shaped much of the law of policing. But now, this understanding of the world is in its last stages of unraveling. In nearly all states, guns are no longer unlawful to own and carry by default. In many, they are barely regulated. Recent Supreme Court Second Amendment decisions like New York State Rifle & Pistol Association v. Bruen serve only to hasten where state laws already were headed. For police, however, the harm guns can do exists irrespective of what the law has to say about the legality of carrying them. As a result, the nation's gun laws are on a collision course with the practice and law of policing. This Article explores how the constitutional law governing policing is changing and will change in the face of gun legalization. Part I of this Article explains the ubiquitous role guns play in the life of a police officer, and what actions guns lead police to take. Part II is about the legal doctrine of policing, both before and after firearm legalization. It details how the law shaped what police could do in order to protect themselves and others, and how that law is changing to accommodate legalization. Police now must operate in a terrain that increasingly is uncertain as to their lawful authority, and that in many instances may put them or others in jeopardy. Part III examines how the shifting laws of guns and policing might impact police behavior, likely resulting in ad hoc carve-outs for police authority that-if history is any guide-overwhelmingly will be imposed on Black and Brown communities.

A new practical imaging technique was presented for metamaterial characterization and investigation by visualizations of the magnetic microwave near-field (H-MWNF) distributions on a metamaterial's surface using the method of thermo-elastic optical indicator microscopy (TEOIM). ITO-based transparent and ceramic-based opaque metamaterial structures were designed for magnetic near-field visualization. Depending on the incident microwave field polarization, the TEOIM system allows the characterization of the metamaterial properties and microwave interaction behavior. The working principle of the periodic structures was investigated through numerical simulations, and the obtained results exhibited strong agreement when compared with experimental observations. Moreover, the visualization of the H-MWNF revealed the potential to characterize and evaluate the absorption and transmission properties effectively., (© 2023. The Author(s).)

Headache is the fifth most common presenting chief complaint in emergency departments, and it is vital to quickly rule out life-threatening secondary causes. Though there are many medications, new and old, that can be used to treat primary headache, the evidence for their effectiveness can be conflicting. This review describes the pathology, workup, and treatment for migraine and other primary headaches based on the best available evidence, including novel medications, nerve blocks, and strategies for preventing postdrome recurrence. Other headache disorders, including cluster headache, medication overuse headache, and chronic migraine are also reviewed.

Contemporary personalized cancer diagnostic approaches encounter multiple challenges. The presence of cellular and molecular heterogeneity in patient samples introduces complexities to analysis protocols. Conventional analyses are manual, reliant on expert personnel, time-intensive, and financially burdensome. The copious data amassed for subsequent analysis strains the system, obstructing real-time diagnostics at the "point of care" and impeding prompt intervention. This study introduces PTOLEMI: Python-based Tensor Oncological Locator Examining Microfluidic Instruments. PTOLEMI stands out as a specialized system designed for high-throughput image analysis, particularly in the realm of microfluidic assays. Utilizing a blend of machine learning algorithms, PTOLEMI can process large datasets rapidly and with high accuracy, making it feasible for point-of-care diagnostics. Furthermore, its advanced analytics capabilities facilitate a more granular understanding of cellular dynamics, thereby allowing for more targeted and effective treatment options. Leveraging cutting-edge AI algorithms, PTOLEMI rapidly and accurately discriminates between cell viability and distinct cell types within biopsy samples. The diagnostic process becomes automated, swift, precise, and resource-efficient, rendering it well-suited for point-of-care requisites. By employing PTOLEMI alongside a microfluidic cell culture chip, physicians can attain personalized diagnostic and therapeutic insights. This paper elucidates the evolution of PTOLEMI and showcases its prowess in analyzing cancer patient samples within a microfluidic apparatus. While the integration of machine learning tools into biomedical domains is undoubtedly in progress, this study's innovation lies in the fusion of PTOLEMI with a microfluidic platform-an integrated, rapid, and independent framework for personalized drug screening-based clinical decision-making.

Purpose: Left atrial calcification (LAC), a primarily radiologic diagnosis, has been associated with rheumatic heart disease (RHD) and rheumatic fever (RF). However, left atrial calcification continues to be observed despite a significant decrease in the prevalence of rheumatic heart disease. The purpose of this study was to investigate other possible etiologies of left atrial calcification., Material and Methods: This retrospective, observational single-center study included patients from 2017 to 2022 identified as having left atrial calcification as well as age- and sex-matched controls. The prevalence of rheumatic heart disease, atrial ablation, and mitral valve disease was compared, and odds ratios were calculated for each independent variable., Results: Sixty-two patients with left atrial calcifications were included and compared with 62 controls. 87.1% of patients in the left atrial calcifications cohort had a history of atrial fibrillation compared with 21% in the control cohort ( p < 0.001). 16.1% of patients in the calcifications cohort presented a history of rheumatic fever compared with zero in the control cohort ( p = 0.004). 66.1% of the left atrial calcifications cohort had a history of atrial ablation compared with 6.5% of the control group ( p < 0.001). The odds ratio for left atrial calcification was 19.0 vs. 4.8 for rheumatic fever (comparative odds = 4.0 for atrial ablation vs. rheumatic fever). Multivariable log model found atrial ablation to explain 79.8% of left atrial calcifications identified., Conclusions: Our study found a 4-fold higher association between history of atrial ablation and left atrial calcification compared with rheumatic heart disease, suggesting a potential shift in etiology., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2023.)

Objective: To characterize the demographics, educational background, and scholarly characteristics of current urology residency program directors (PDs)., Methods: Urology programs were identified by the listing on the "Accredited US Urology Programs" section of American Urological Association website as of October 2021. Demographics and academic data were collected via publicly available department website and Google search engine. Metrics obtained included years of service as PD from time of appointment, sex, medical school/residency/fellowship, all-time H-index, dual degrees obtained, and professorial ranking., Results: One hundred and forty-seven accredited urological residencies were reviewed; every PD was included. The majority were male (78%) and fellowship trained (68%). Women represented only 22% of PDs. The median active time served as PD, as of 11/2021, was 4years (IQR: 2-7). Forty (28%) were faculty at the same program they completed their residency. The median all-time H-index was 12 (IQR: 7-19; range 1-61). Twelve PDs also served as chair of their department., Conclusion: The vast majority of PDs are male, fellowship trained, and have served for less than 5years. Future studies are necessary to follow the trends of representation in leaders of urology residency programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In the United States, sex-trafficking awareness and prevention has increasingly become part of government-mandated health education. This exploratory study surveyed 250 U.S. adolescents to learn more about the use of media narratives in curricula about sex trafficking in light of research findings about victim-blaming responses to survivor narratives, as well as adolescents' still-developing emotion-regulation skills. Victim blaming is counterproductive to the goals of trafficking awareness and prevention curricula. Participants viewed one of four narrative messages about a sex-trafficking victim/survivor. Over half of participants reported victim-blaming responses after viewing the message. Participants reported low perceived efficacy regarding the ability to recognize the signs of trafficking, and some participants experienced intense fear responses to the messages. Victim blaming was not associated with fear or perceived efficacy, contradicting predictions from the Extended Parallel Process Model. This study concludes with recommendations for educators and others tasked with communicating with adolescents about sex trafficking.

The International Standards Organization 81060-2:2018 is the current global Standard for the validation of automated sphygmomanometers. It specifies the requirements for clinical studies on the general population, as well as additional requirements for special populations, which might have physiologic characteristics that affect the accuracy of blood pressure measurements. This paper summarizes the statistical methodology behind the sample size required to test automated sphygmomanometers in these special populations and specifically addresses the pregnant patient population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The recent development of high spatial resolution microscopy and spectroscopy tools enabled reactivity analysis of homogeneous and heterogeneous (electro)catalysts at previously unattainable resolution and sensitivity. These techniques revealed that catalytic entities are more heterogeneous than expected and local variations in reaction mechanism due to divergences in the nature of active sites, such as their atomic properties, distribution, and accessibility, occur both in homogeneous and heterogeneous (electro)catalysts. In this review, we highlight recent insights in catalysis research that were attained by conducting high spatial resolution studies. The discussed case studies range from reactivity detection of single particles or single molecular catalysts, inter- and intraparticle communication analysis, and probing the influence of catalysts distribution and accessibility on the resulting reactivity. It is demonstrated that multiparticle and multisite reactivity analyses provide unique knowledge about reaction mechanism that could not have been attained by conducting ensemble-based, averaging, spectroscopy measurements. It is highlighted that the integration of spectroscopy and microscopy measurements under realistic reaction conditions will be essential to bridge the gap between model-system studies and real-world high spatial resolution reactivity analysis.

Osteoarthritis (OA) pathogenesis is associated with reduced chondrocyte homeostasis and increased levels of cartilage cellular senescence. Chondrosenescence is the development of cartilage senescence that increases with aging joints and disrupts chondrocyte homeostasis and is associated with OA. Adenosine A2A receptor (A2AR) activation in cartilage via intra-articular injection of liposomal A2AR agonist, liposomal-CGS21680, leads to cartilage regeneration in vivo and chondrocyte homeostasis. A2AR knockout mice develop early OA isolated chondrocytes demonstrate upregulated expression of cellular senescence and aging-associated genes. Based on these observations, we hypothesized that A2AR activation would ameliorate cartilage senescence. We found that A2AR stimulation of chondrocytes reduced beta-galactosidase staining and regulated levels and cell localization of common senescence mediators p21 and p16 in vitro in the human TC28a2 chondrocyte cell line. In vivo analysis similarly showed A2AR activation reduced nuclear p21 and p16 in obesity-induced OA mice injected with liposomal-CGS21680 and increased nuclear p21 and p16 in A2AR knockout mouse chondrocytes compared to wild-type mice. A2AR agonism also increased activity of the chondrocyte Sirt1/AMPK energy-sensing pathway by enhancing nuclear Sirt1 localization and upregulating T172-phosphorylated (active) AMPK protein levels. Lastly, A2AR activation in TC28a2 and primary human chondrocytes reduced wild-type p53 and concomitantly increased p53 alternative splicing leading to increase in an anti-senescent p53 variant, Δ133p53α. The results reported here indicate that A2AR signaling promotes chondrocyte homeostasis in vitro and reduces OA cartilage development in vivo by reducing chondrocyte senescence., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Drosophila melanogaster reproductive behaviors are orchestrated by fruitless neurons. We performed single-cell RNA-sequencing on pupal neurons that produce sex-specifically spliced fru transcripts, the fru P1-expressing neurons. Uniform Manifold Approximation and Projection (UMAP) with clustering generates an atlas containing 113 clusters. While the male and female neurons overlap in UMAP space, more than half the clusters have sex differences in neuron number, and nearly all clusters display sex-differential expression. Based on an examination of enriched marker genes, we annotate clusters as circadian clock neurons, mushroom body Kenyon cell neurons, neurotransmitter- and/or neuropeptide-producing, and those that express doublesex . Marker gene analyses also show that genes that encode members of the immunoglobulin superfamily of cell adhesion molecules, transcription factors, neuropeptides, neuropeptide receptors, and Wnts have unique patterns of enriched expression across the clusters. In vivo spatial gene expression links to the clusters are examined. A functional analysis of fru P1 circadian neurons shows they have dimorphic roles in activity and period length. Given that most clusters are comprised of male and female neurons indicates that the sexes have fru P1 neurons with common gene expression programs. Sex-specific expression is overlaid on this program, to build the potential for vastly different sex-specific behaviors., Competing Interests: CP, CA, SB, BF, AG, MA No competing interests declared, (© 2023, Palmateer et al.)

Healthcare personnel (HCP) are at potential risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in occupational and nonoccupational settings, even when fully vaccinated. This risk increased during Delta variant circulation. SARS-CoV-2 testing of fully vaccinated HCP working in the 14 days after exposure is important to prevent virus introduction into healthcare settings., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess the impact of post-thawing embryo culture on frozen embryo transfer (FET) outcomes., Methods: A retrospective cohort study including 678 consecutive FET cycles performed between the years 2004 and 2017 was conducted. Patients older than 45 years old were excluded. FET cycles were stratified as follows: (1) two-day (2d) embryos thawed and cultured to three-day (3d) versus 3d embryos thawed and transferred; (2) 2d or 3d embryos thawed and cultured to blastocysts versus blastocysts thawed and transferred. A p -value <.05 was considered statistically significant., Results: Maternal age, BMI, smoking, and basal FSH of the 2d and 3d cultured embryo group ( n  = 110) and the 3d non-cultured embryo group ( n  = 189) were comparable. Endometrium preparation protocols and the achieved endometrial thickness did not differ between groups. Pregnancy rate, implantation rate, clinical pregnancy, live birth rate, abortions, multiple pregnancies, perinatal outcomes, and birth weight were comparable.The 2d and 3d embryos cultured to blastocyst ( n  = 41) compared to non-cultured blastocyst ( n  = 338) showed that the non-cultured blastocyst patients had higher smoking rates and longer follicular phase. Endometrial thickness was comparable. The 2d and 3d embryos cultured to blastocyst stage had higher multiple pregnancies rate compared to the blastocyst non-cultured group, whereas pregnancy rate, implantation rate, live birth rate, miscarriages, perinatal outcomes, and birth weight were comparable., Conclusion: We could not demonstrate that the post-thaw culture had a significant impact on the outcome of FET cycles.

Abstract: Ethical allocation of scare medical resources is a ubiquitous challenge in many, if not all, medical specialties. The field of physical medicine and rehabilitation is no exception and presents its own unique dilemmas. We report on a small inpatient rehabilitation unit at a large university medical center with a large catchment area representing a vast range of socioeconomic classes. The decision of whom to admit is a constant challenge. We review the existing literature regarding ethical considerations in rehabilitation department admission criteria and attempt to analyze criteria used to admit patients to a general physical medicine and rehabilitation ward. Finally, we discuss our medical center approach to the ethical dilemma of admission priority. A systemic search was conducted in six sources (PubMed, Google Scholar, ScienceDirect, Cochrane Library, LILACS, Embase). Searches were limited to English language articles with no date restriction, reflecting all available data. A reviewer applied the inclusion criteria to identify relevant articles.This review highlights a number of important ethical issues in evaluation and selection criteria that may assist clinicians in improving selection procedures and standardizing access to inpatient rehabilitation. Further high-quality empirical studies and reviews of ethical admission practice with regard to rehabilitation acceptance are required., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Interactions between radiologists and emergency physicians are often diminished as imaging volume increases and more radiologists read off site. We explore how several commonly used phrasings are perceived by radiologists and emergency physicians to decrease ambiguity in reporting., Methods: An anonymous survey was distributed to attendings and residents at seven academic radiology and emergency departments across the USA via a digital platform as well as to an email group consisting of radiologists across the country with an interest in quality assurance. Physicians were asked to assign a percent score to probabilistic phrases such as, "suspicious of," or "concerned for." Additional questions including, "how often the report findings are reviewed," "what makes a good radiology report," and "when is it useful to use the phrase 'clinical correlation are recommended.'" Median scores and confidence intervals were compared using an independent Student's T-test., Results: Generally, there was agreement between radiologists and emergency room physicians in how they interpret probabilistic phrases except for the phrases, "compatible with," and "subcentimeter liver lesions too small to characterize." Radiologists consider a useful report to answer the clinical question, be concise, and well organized. Emergency physicians consider a useful report to be concise, definitive or include a differential diagnosis, answer the clinical question, and recommend a next step. Radiologists and emergency physicians did not agree on the usefulness of the phrase, "clinical correlation recommended," in which radiologists found the phrase more helpful under particular circumstances., Conclusion: The survey demonstrated a wide range of answers for probabilistic phrases for both radiologists and emergency physicians. While the medians and means of the two groups were often different by statistical significance, the actual percent difference was minor. These wide range of answers suggest that use of probabilistic phrases may sometimes lead to misinterpretation between radiologist and emergency room physician and should be avoided or defined if possible., (© 2022. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Purpose: To assess the association between BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and the risk of active noninfectious uveitis (NIU)., Design: Retrospective, population-based study., Participants: Two million six hundred two thousand five hundred fifty-seven people who received the first vaccine dose between December 20, 2020, and April 30, 2021, and 2 441 719 people who received the second vaccine dose between January 10, 2021, and April 30, 2021., Methods: Events of active NIU were included if they occurred within 21 days after either vaccine dose. Active NIU was defined as newly active or worsening ocular inflammation requiring initiation or increase in local or systemic corticosteroids. Observed cases were compared with the expected number, based on the experience of the population in 2019., Main Outcome Measures: Age- and sex-adjusted standardized incidence ratios (SIRs) and attributable risks after BNT126b2 vaccination., Results: Overall, 100 and 88 events of active NIU were recorded within 21 days after the first and second vaccine doses, respectively. Using the experience of the population in 2019 as a reference, after the first dose, the estimated age- and sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15-1.71) along with a 21-day attributable risk of 1.12 cases per 100 000 vaccinees. After the second dose, the SIR was 1.31 (95% CI, 1.05-1.62), with an estimated attributable risk of 0.86 cases per 100 000 vaccinees. Anterior uveitis was the most common site of inflammation, occurring in 90.96% of eyes, and idiopathic uveitis was the most common cause (56.38%)., Conclusions: This study suggests that the BNT162b2 mRNA COVID-19 vaccine may be associated with an increased risk of active NIU. However, considering the small effect size and study limitations, this study does not provide proof for a cause-and-effect relationship. The small estimated attributable risks suggest that the impact on public health is relatively minor., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

A key feature of chromosome segregation is the ability to sense tension between sister kinetochores. DNA between sister kinetochores must be packaged in a way that sustains tension propagation from one kinetochore to its sister, approximately 1 micron away. A molecular bottlebrush consisting of a primary axis populated with a crowded array of side chains provides a means to build tension over length scales considerably larger than the stiffness of the individual elements, that is, DNA polymer. Evidence for the bottlebrush organization of chromatin between sister kinetochores comes from genetic, cell biological, and polymer modeling of the budding yeast centromere. In this study, we have used polymer dynamic simulations of the bottlebrush to recapitulate experimental observations of kinetochore structure. Several aspects of the spatial distribution of kinetochore proteins and their response to perturbation lack a mechanistic understanding. Changes in physical parameters of bottlebrush, DNA stiffness, and DNA loops directly impact the architecture of the inner kinetochore. This study reveals that the bottlebrush is an active participant in building tension between sister kinetochores and proposes a mechanism for chromatin feedback to the kinetochore.

Background: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation., Methods: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk., Results: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed., Conclusions: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.)., (Copyright © 2022 Massachusetts Medical Society.)

A woman in her 30s presented to the dermatology clinic with widespread, pruritic, red papules and plaques involving the ears, trunk and extremities. The rash developed a few days after receiving her second injection of secukinumab, which was initiated for recalcitrant Hurley stage III hidradenitis suppurativa. Investigations revealed a psoriasiform drug hypersensitivity reaction secondary to secukinumab. In this report, we describe the clinical course, histopathological correlation and treatment of this rarely documented reaction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Visualizations of the microwave electric and magnetic near-field distributions of radio-frequency (RF) filters were performed using the technique of thermoelastic optical indicator microscopy (TEOIM). New optical indicators based on periodic dielectric-metal structures were designed for electric field visualization. Depending on the structure orientation, such metasurface-based indicators allow separately visualization of the E x and E y components of the in-plane electric field. Numerical simulations were conducted to examine the working principle of the designed indicator structures, and the results were compared to the experimental, showing good agreement. In addition, the 3D visualization of the microwave near-field distribution was built, to show the field intensity and distribution dependencies on the distance from the RF filter., (© 2022. The Author(s).)

Monetary sanctions are an integral and increasingly debated feature of the American criminal legal system. Emerging research, including that featured in this volume, offers important insight into the law governing monetary sanctions, how they are levied, and how their imposition affects inequality. Monetary sanctions are assessed for a wide range of contacts with the criminal legal system ranging from felony convictions to alleged traffic violations with important variability in law and practice across states. These differences allow for the identification of features of law, policy, and practice that differentially shape access to justice and equality before the law. Common practices undermine individuals' rights and fuel inequality in the effects of unpaid monetary sanctions. These observations lead us to offer a number of specific recommendations to improve the administration of justice, mitigate some of the most harmful effects of monetary sanctions, and advance future research.

Purpose: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC., Materials and Methods: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial., Results: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue., Conclusions: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Autosomal dominant polycystic kidney disease (ADPKD) eventually leads to end stage renal disease (ESRD) with an increase in size and number of cysts over time. Progression to ESRD has previously been shown to correlate with total kidney volume (TKV). An accurate and relatively simple method to perform measurement of TKV has been difficult to develop. We propose a semi-automated approach of calculating TKV inclusive of all cysts in ADPKD patients based on b0 images relatively quickly without requiring any calculations or additional MRI time. Our purpose is to evaluate the reliability and reproducibility of our method by raters of various training levels within the environment of an advanced 3D viewer. Thirty patients were retrospectively identified who had DWI performed as part of 1.5T MRI renal examination. Right and left TKVs were calculated by five radiologists of various training levels. Interrater reliability (IRR) was estimated by computing the intraclass correlation (ICC) for all raters. ICC values calculated for TKV measurements between the five raters were 0.989 (95% CI = (0.981, 0.994), p < 0.01) for the right and 0.961 (95% CI = (0.936, 0.979), p < 0.01) for the left. Our method shows excellent intraclass correlation between raters, allowing for excellent interrater reliability.

Adenosine signaling plays a critical role in the maintenance of articular cartilage and may serve as a novel therapeutic for osteoarthritis (OA), a highly prevalent and morbid disease without effective therapeutics in the current market. Mice lacking adenosine A2A receptors (A2AR) develop spontaneous OA by 16 weeks of age, a finding relevant to human OA since loss of adenosine signaling due to diminished adenosine production (NT5E deficiency) also leads to development of OA in mice and humans. To better understand the mechanism by which A2AR and adenosine generation protect from OA development, we examined differential gene expression in neonatal chondrocytes from WT and A2AR null mice. Analysis of differentially expressed genes was analyzed by KEGG pathway analysis, and oPOSSUM and the flatiron database were used to identify transcription factor binding enrichment, and tissue-specific network analyses and patterns were compared to gene expression patterns in chondrocytes from patients with OA. There was a differential expression of 2211 genes (padj<0.05). Pathway enrichment analysis revealed that pro-inflammatory changes, increased metalloprotease, reduced matrix organization, and homeostasis are upregulated in A2AR null chondrocytes. Moreover, stress responses, including autophagy and HIF-1 signaling, seem to be important drivers of OA and bear marked resemblance to the human OA transcriptome. Although A2AR null mice are born with grossly intact articular cartilage, we identify here the molecular foundations for early-onset OA in these mice, further establishing their role as models for human disease and the potential use of adenosine as a treatment for human disease., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, a KA manifests as a rapidly growing, well-differentiated, squamoid lesion with a predilection for sun-exposed sites in elderly people and a tendency to spontaneously regress. Historically, KAs have been considered a variant of cutaneous squamous cell carcinoma (cSCC) and are often reported as KA-type cSCC. However, the penchant for regression has led many to categorize KAs as biologically benign tumours with distinct pathophysiological mechanisms from malignant cSCC. The clinical and histopathological similarities between KA and cSCC, particularly the well-differentiated variant of cSCC, have made definitive differentiation difficult or impossible in many cases. The ambiguity between entities has led to the general recommendation for surgical excision of KAs to ensure a potentially malignant cSCC is not left untreated. This current standard creates unnecessary surgical morbidity and financial strain for patients, especially the at-risk elderly population. There have been no reports of death from a definitive KA to date, while cSCC has an approximate mortality rate of 1·5%. Reliably distinguishing cSCC from KA would shift management strategies for KAs towards less-invasive treatment modalities, prevent unnecessary surgical morbidity, and likely reduce associated healthcare costs. Herein, we review the pathophysiology and clinical characteristics of KA, and conclude on the balance of current evidence that KA is a benign lesion and distinct from cSCC., (© 2021 British Association of Dermatologists.)

Introduction: Variations in laser pulse energy and it's frequency during lithotripsy, affect the rate and the method of stone breaking. The main modes of lithotripsy are dusting and fragmentation., Aims: Comparison between long term results of dusting versus fragmentation, by defining the stone free rate (SFR) for each method and the time period until re-treatment need., Methods: Clinical and radiological follow-up of 43 patients who underwent laser intervention using dusting or fragmentation. Both groups shared similar demographic features, stone sizes and locations. For each group, the percentage of patients without stones requiring intervention during the follow-up period of 36 months was defined as a success parameter. The incidence of emergency department (ED) admissions and auxiliary interventions were assessed., Results: Thirty-eight patients were included in the study. No difference in the median period of time to clinically significant stone was seen (p=0.213). No difference was found in SFR between the dusting (83.3%) and the fragmentation (84.6%) groups respectively (p=1.000). No statistically significant difference was shown in ED admissions due to renal colic occurring in 31.6% and 10.5% within dusting and fragmentation groups respectively (p=0.116)., Conclusions: No difference in time period until clinically significant stone appearance was seen. No significant difference in SFR was found between the groups at the long term follow-up., Discussion: It seems that within the dusting group, the ED admission rate could be somewhat higher. However, this impression lacks statistical significance. A long term prospective study with a larger population is needed to confirm these results.

Background: Reports have indicated an association of large vessel peripheral arterial occlusion in the setting of Coronavirus Disease 2019 (COVID-19). While prior investigations have mostly focused on venous or cerebral arterial occlusions, we examined patients presenting exclusively with peripheral arterial extremity occlusions to investigate for any predisposing factors in this subset of COVID-19 patients., Materials and Methods: This is a retrospective study of COVID-19 patients with peripheral arterial occlusions presenting to a multi-hospital health care system in New York City between February 1st, 2020 and April 30th, 2020. Patient data and computed tomography angiography (CTA) exams in this subset were then collected and analyzed., Results: For the months of February, March, and April 2020, we identified 9 patients (ages 37-93 yrs) at our health care system who underwent extremity CTA for large vessel upper or lower extremity arterial occlusion and were diagnosed with COVID-19. Patient medical histories and clinical parameters were evaluated to identify common risk factors including obesity, hypertension, hyperlipidemia, and diabetes. Patients presented with increased inflammatory markers including ferritin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as increased D-dimer., Conclusion: Our findings suggest patients with COVID-19 and comorbidities presenting with elevated inflammatory markers and D-dimer may be at increased risk of large vessel peripheral arterial occlusion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors., Competing Interests: JT, JP, JL, SL, PT, BH, SZ, DK, BF, FW No competing interests declared, (© 2021, Takatoh et al.)

The microvasculature underlies the supply networks that support neuronal activity within heterogeneous brain regions. What are common versus heterogeneous aspects of the connectivity, density, and orientation of capillary networks? To address this, we imaged, reconstructed, and analyzed the microvasculature connectome in whole adult mice brains with sub-micrometer resolution. Graph analysis revealed common network topology across the brain that leads to a shared structural robustness against the rarefaction of vessels. Geometrical analysis, based on anatomically accurate reconstructions, uncovered a scaling law that links length density, i.e., the length of vessel per volume, with tissue-to-vessel distances. We then derive a formula that connects regional differences in metabolism to differences in length density and, further, predicts a common value of maximum tissue oxygen tension across the brain. Last, the orientation of capillaries is weakly anisotropic with the exception of a few strongly anisotropic regions; this variation can impact the interpretation of fMRI data., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)