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We describe a Lanczos-based algorithm for approximating the product of a rational matrix function with a vector. This algorithm, which we call the Lanczos method for optimal rational matrix function approximation (Lanczos-OR), returns the optimal approximation from a given Krylov subspace in a norm depending on the rational function's denominator, and can be computed using the information from a slightly larger Krylov subspace. We also provide a low-memory implementation which only requires storing a number of vectors proportional to the denominator degree of the rational function. Finally, we show that Lanczos-OR can be used to derive algorithms for computing other matrix functions, including the matrix sign function and quadrature based rational function approximations. In many cases, it improves on the approximation quality of prior approaches, including the standard Lanczos method, with little additional computational overhead.

Purpose: To evaluate the differences in corneal wavefront measurements in myopic and hyperopic eyes when calculated using three different reference centers and explore possible influencing factors for such differences. Methods: Corneal wavefront measurements were performed in myopic and hyperopic eyes using a GALILEI Placido Dual Scheimpflug Analyzer (Ziemer Ophthalmic Systems AG). Corneal higher order aberrations (HOAs), including total, vertical, and horizontal coma-like aberrations, spherical aberrations, and total corneal HOAs through a 6-mm pupil size, were calculated over three different reference center positions: pupil center, corneal vertex, and limbus to limbus. Values were then compared between the myopic and hyper-opic eyes, and correlations with kappa distance and spherical equivalent were tested. Results: A significant decrease in the level of total corneal HOAs (−0.04 ± 0.05 and −0.12 ± 0.09), total corneal coma (−0.07 ± 0.09 and −0.18 ± 0.12), and horizontal coma (−0.07 ± 0.11 and −0.22 ± 0.11) in myopic and hyperopic eyes, respectively, was found when recalculating from pupil center to corneal vertex centration, whereas a significant increase in the same aberrations was observed from pupil center or corneal vertex to limbus to limbus. Significant correlations were found between the kappa distance and changes in total corneal HOAs, total corneal coma, and horizontal coma from the pupil center to the corneal vertex in both groups. Conclusions: Corneal vertex centration generated the lowest level of corneal wavefront error in both groups. The differences in corneal aberrations between the reference centers for calculation were highly correlated with the kappa distance in hyperopic eyes. [ J Refract Surg . 2023;39(5):340–346.]

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade. Taken together, results from this cohort demonstrate the complexity of biological determinants underlying immunotherapy outcomes and reinforce the discovery potential of integrative analysis within large, well-curated, cancer-specific cohorts.

Dhaka's National Assembly building, designed by Louis Kahn, was built over several turbulent decades as East Pakistan fought for autonomy and became the new country of Bangladesh. Conventional critical narratives situate the National Assembly within Kahn's biography, treating Bangladesh as an empty canvas on which Kahn could enact design philosophies developed over his career. I contend that architects and critics are not the only arbiters of a building's meaning, and that local and political context should not be ignored in a building's historical narrative. There is ample recent scholarship decentering the Western canon, to which the National Assembly belongs, in architecture history, theory, and criticism. This article calls for decentering the architect as well, and acknowledging that the client's agenda, historical context, local interventions, popular perception, and the ongoing use of a building all influence the many layers of meaning architecture acquires over time. Continuing to perpetuate the myth of the lone artistic genius doggedly pursuing his creative vision gives unfounded agency to the individual architect alone. Design has agency and buildings shape worlds, but buildings themselves are shaped by complex collective actions, not singular visions. As a Western architect called to build on a grand scale in Asia, Kahn is an early example of a now prevalent trope. This research establishes a template for understanding this kind of work in context, and acknowledging the crucial role played by local actors in shaping each project and determining the project's cultural significance over time.

A growing body of research has examined the construct of bottom-line mentality (BLM), which captures a tunnel vision focus on securing bottom-line outcomes to the disregard of competing work priorities. We offer a systematic review of the literature to summarize current knowledge of BLM, what is missing in the literature, and key opportunities for advancing our theoretical understanding of the construct. Our review first defines and conceptualizes BLM and then organizes past BLM findings according to the key sources of BLM: (a) leader, (b) employee, and (c) collective BLM. When applicable, research on each source of BLM is synthesized with respect to its most prevalent theoretical frameworks and in relation to its (a) outcomes, (b) antecedents, and (c) instances whereby BLM serves as a moderator. Our discussion then examines the critical ways in which BLM research can advance with the most theoretical rigor. We first discuss whether there is value in studying a BLM with respect to non-financial, bottom-line outcomes. Second, we question whether BLMs always (or mostly) foster the desired bottom-line outcome. Third, we provide theoretical arguments that support BLM as a potentially activated psychological state that is driven by context and suggest specific contexts that could be the driving forces of BLMs at work. Finally, we discuss the ways in which BLM research can improve methodologically, including a suggestion of how to revise the current BLM measure to advance BLMs with respect to non-financial, bottom-line outcomes.

Objectives To explore the knowledge and skills of pharmacists practicing in Sydney, Australia, in preventing the use of prohibited medications by athletes. Methods Using a simulated-patient study design, the researcher (an athlete and pharmacy student herself) contacted 100 Sydney pharmacies by telephone requesting advice about taking a salbutamol inhaler (a WADA-prohibited substance with conditional requirements), for exercise-induced asthma, following a set interview protocol. Data were assessed for both clinical and anti-doping advice appropriateness. Key findings Appropriate clinical advice was provided by 66% of pharmacists in the study, appropriate anti-doping advice was provided by 68%, and 52% provided appropriate advice across both aspects. Of the respondents, only 11% provided both clinical and anti-doping advice at a comprehensive level. Identification of accurate resources was made by 47% of pharmacists. Conclusions Whilst most participating pharmacists had the skills to deliver assistance regarding the use of prohibited substances in sports, many lacked core knowledge and resources to enable them to deliver comprehensive care to prevent harm and protect athlete-patients from anti-doping violations. A gap was identified regarding advising/counselling athletes, indicating the need for additional education in sport-related pharmacy. This education would need to be coupled with the incorporation of sport-related pharmacy into current practice guidelines to enable pharmacists to uphold their duty of care and for athletes to benefit from their medicines-related advice.

We aim to compare in-hospital and 30-day outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) for native aortic insufficiency (AI).TAVR is increasingly used off-label in patients with AI deemed high risk for SAVR. There is a paucity of data comparing TAVR and SAVR with current commercially available TAVR devices.A single-center, retrospective cohort study of patients undergoing TAVR or SAVR for native AI between 2014 and 2020 was performed. Data were obtained from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, Transcatheter Valve Therapy (TVT) registry, and chart review. In-hospital and 30-day outcomes are reported.Of 125 total patients, 91 underwent SAVR and 34 underwent TAVR. The TAVR group had a higher STS predictive risk of mortality (PROM) (TAVR = 3.96 %, SAVR = 1.25 %, p0.0001). In the postoperative period, the SAVR group had higher rates of new-onset atrial fibrillation (20.9 % vs. 0 %, p0.001), while the TAVR group had higher rates of complete heart block requiring permanent pacemaker implantation (20.6 % vs. 2.2 %, p0.001). There was no difference in in-hospital or 30-day mortality, stroke, myocardial infarction, residual AI, or repeat valve intervention.Despite higher STS PROM and more comorbidities, patients who underwent TAVR for AI had similar in-hospital and 30-day outcomes as patients who underwent SAVR for AI. These results support TAVR in selected high-risk patients with AI, with the knowledge that pacemaker needs may be higher than patients undergoing SAVR.

BACKGROUND: Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children/adolescents with ADPKD. METHODS: This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR ≥60 ml/min per 1.73 m2. Participants aged 12-17 years were the target group (group 1, enrollment goal n≥60); participants aged 4-11 years could additionally enroll (group 2, anticipated enrollment approximately 40). Treatments were tolvaptan or placebo titrated by body weight and tolerability. Coprimary end points, change from baseline in spot urine osmolality and specific gravity at week 1, assessed inhibition of antidiuretic hormone activity. The key secondary end point was change in height-adjusted total kidney volume (htTKV) to month 12 in group 1. Additional end points were safety/tolerability and quality of life. Statistical comparisons were exploratory and post hoc. RESULTS: Among the 91 randomized (group 1, n=66; group 2, n=25), least squares (LS) mean reduction (±SEM) in spot urine osmolality at week 1 was greater with tolvaptan (-390 [28] mOsm/kg) than placebo (-90 [29] mOsm/kg; P0.05). For tolvaptan and placebo, respectively, 65% and 16% of subjects experienced aquaretic adverse events, and 2% and 0% experienced hypernatremia. There were no elevated transaminases or drug-induced liver injuries. Four participants discontinued tolvaptan, and three discontinued placebo. Quality-of-life assessments remained stable. CONCLUSIONS: Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273. ispartof: CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY vol:18 issue:1 pages:36-46 ispartof: location:United States status: published

Organophosphate flame retardants (OPFRs) have become the predominant substitution for legacy brominated flame retardants but there is concern about their potential developmental neurotoxicity (DNT). OPFRs readily dissociate from the fireproofed substrate to the environment, and they (or their metabolites) have been detected in diverse matrices including air, water, soil, and biota, including human urine and breastmilk. Given this ubiquitous contamination, it becomes increasingly important to understand the potential effects of OPFRs on the developing nervous system. We have previously shown that maternal exposure to OPFRs results in neuroendocrine disruption, alterations to developmental metabolism of serotonin (5-HT) and axonal extension in male fetal rats, and potentiates adult anxiety-like behaviors. The development of the serotonin and dopamine systems occur in parallel and interact, therefore, we first sought to enhance our prior 5-HT work by first examining the ascending 5-HT system on embryonic day 14 using whole mount clearing of fetal heads and 3-dimensional (3D) brain imaging. We also investigated the effects of maternal OPFR exposure on the development of the mesocortical dopamine system in the same animals through 2-dimensional and 3D analysis following immunohistochemistry for tyrosine hydroxylase (TH). Maternal OPFR exposure induced morphological changes to the putative ventral tegmental area and substantia nigra in both sexes and reduced the overall volume of this structure in males, whereas 5-HT nuclei were unchanged. Additionally, dopaminergic axogenesis was disrupted in OPFR exposed animals, as the dorsoventral spread of ventral telencephalic TH afferents were greater at embryonic day 14, while sparing 5-HT fibers. These results indicate maternal exposure to OPFRs alters the development trajectory of the embryonic dopaminergic system and adds to growing evidence of OPFR DNT.

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a M Jup widely separated (∼8″, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color–magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256 b with JWST's NIRSpec IFU and MIRI MRS modes for coverage from 1 to 20 μm at resolutions of ∼1000–3700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the JWST spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion.

Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited.A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure.Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe ( 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score 4 on kidney biopsy were associated with kidney failure.Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

The use of bioprosthetic prostheses during surgical aortic valve replacements has increased dramatically over the last two decades, accounting for over 85% of surgical implantations. Given limited long-term durability, there has been an increase in aortic valve reoperations and reinterventions. With the advent of new technologies, multiple treatment strategies are available to treat bioprosthetic valve failure, including valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR). However, ViV TAVR has an increased risk of higher gradients and patient prosthesis mismatch (PPM) secondary to placing the new valve within the rigid frame of the prior valve, especially in patients with a small surgical bioprosthesis in situ. Bioprosthetic valve fracture allows for placement of a larger transcatheter valve, as well as a fully expanded transcatheter valve, decreasing postoperative gradients and the risk of PPM.

Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM.Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%.Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival.MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.

Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.

Over the past 60 years, scientists have strived to understand the past, present and future of the Antarctic Ice Sheet. One of the key components of this research has been the mapping of Antarctic bed topography and ice thickness parameters that are crucial for modelling ice flow and hence for predicting future ice loss and ensuing sea level rise. Supported by the Scientific Committee on Antarctic Research (SCAR), the Bedmap3 Action Group aims not only to produce new gridded maps of ice thickness and bed topography for the international scientific community, but also to standardize and make available all the geophysical survey data points used in producing the Bedmap gridded products. Here, we document the survey data used in the latest iteration, Bedmap3, incorporating and adding to all of the datasets previously used for Bedmap1 and Bedmap2, including ice-bed, surface and thickness point data from all Antarctic geophysical campaigns since the 1950s. More specifically, we describe the processes used to standardize and make these and future survey and gridded datasets accessible under the ‘Findable, Accessible, Interoperable and Reusable’ (FAIR) data principles. With the goals to make the gridding process reproducible and to allow scientists to re-use the data freely for their own analysis, we introduce the new SCAR Bedmap Data Portal (bedmap.scar.org, last access: 18 October 2022) created to provide unprecedented open access to these important datasets, through a user-friendly webmap interface. We believe that this data release will be a valuable asset to Antarctic research and will greatly extend the life cycle of the data held within it. Data are available from the UK Polar Data Centre: https://data.bas.ac.uk.

Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

Black men who have sex with men (MSM) carry the greatest burden of new HIV diagnoses in the United States. Ending the HIV epidemic requires strategic, culturally specific approaches to target factors contributing to persistent HIV disparities.Safe Spaces 4 Sexual Health (SS4SH), a community-informed HIV/sexually transmitted infection (STI) testing strategy combining mobile van testing with online outreach, was implemented over a 14-month period from 2018 to 2019 in Baltimore, MD.We evaluated the reach of MSM at high risk with high acquisition or transmission risk by SS4SH mobile van combined with online outreach as compared with the Baltimore City Health Department's venue-based mobile van (with no online outreach) operating during the same period based on the following HIV/STI testing outcome measures: (1) number of MSM HIV or STI tested, (2) new HIV diagnosis rate, (3) percent with new syphilis diagnosis, (4) percent at high risk for HIV acquisition, and (5) percent people living with HIV at high risk for transmission.Over a 14-month period, SS4SH HIV/STI tested 151 MSM. Of these, 74% were Black and the mean age was 34 (SD = 10, range = 19-68). Seven percent (10/148) were new HIV diagnoses, and 10% (13/130) were diagnosed with syphilis. The Baltimore City Health Department's venue-based mobile van strategy yielded 53% (231) more MSM (71% Black, mean age 38, SD = 14, range = 15-74), but the HIV/syphilis positivity rate was significantly lower: 0.5% new HIV diagnosis rate (P0.001) and 0.5% with syphilis diagnosis (P0.001).Our findings suggest SS4SH combing online outreach with mobile van testing may be more effective at reaching high-risk Black MSM than venue-based mobile testing.

The geographically widespread species Afrixalus laevis (Anura: Hyperoliidae) currently has a disjunct distribution in western Central Africa (Cameroon, Equatorial Guinea, Gabon, and possibly adjacent countries) and the area in and near the Albertine Rift in eastern Democratic Republic of the Congo and neighboring countries. At least two herpetologists have previously suggested that these disjunct populations represent distinct species, and herein, we utilize an integrative taxonomic approach with molecular and morphological data to reconcile the taxonomy of these spiny reed frogs. We sequenced 1554 base pairs of the 16S and RAG1 genes from 34 samples of A. laevis and one sample of A. orophilus (sympatric with eastern populations of A. laevis), and combined these data with previously sequenced GenBank Afrixalus samples via the bioinformatics toolkit SuperCRUNCH. Phylogenetic trees, dated phylogenetic analyses, and species-delimitation analyses were generated with RAxML, BEAST, and BPP, respectively. Eleven mensural characters were taken from multiple specimens of A. laevis and A. orophilus, and compared with paired t-tests and analyses of covariance. These combined results suggested populations of A. laevis in western Central Africa (Cameroon and Bioko Island, Equatorial Guinea) represent one species, whereas populations from the Albertine Rift and nearby forests represent two undescribed taxa that are sister to A. dorsimaculatus. The two new species (A. lacustris sp. nov. and A. phantasma sp. nov.) are distinguished by our phylogenetic and species-delimitation analyses, significant differences in several mensural characters, qualitative morphological differences, and by their non-overlapping elevational distribution.

Evaluating the impact of delayed care, secondary to coronavirus disease 2019 (COVID-19) pandemic lockdowns, on visual acuity in previously treated neovascular age-related macular degeneration (nAMD) patients.This was a multicenter, retrospective, study of patients with nAMD previously treated with anti-VEGF injections who were followed up during 2019 (pre-COVID-19) and compared with patients with nAMD during 2020 (COVID-19).A total of 1,192 patients with nAMD with a mean age of 81.5 years met the inclusion criteria. Of these, 850 patients were assessed in 2019 (pre-COVID-19) and 630 patients were assessed in 2020 (COVID-19). Three hundred eight patients were assessed through both 2019 and 2020 and thus were included in both cohorts. There was no significant difference between 2020 and 2019 in baseline and change in best-corrected visual acuity (BCVA; P = 0.342 and P = 0.911, respectively). The mean number of anti-VEGF injections was significantly lower (5.55 vs. 6.13, P0.01), with constant lower ratio of injections per patient in the COVID-19 period. Baseline BCVA (0.859, P0.01), number of injections (-0.006, P = 0.01), and age (0.003, P0.01) were predictors of final BCVA.In patients with nAMD, delayed care secondary to COVID-19 pandemic lockdowns has no statistically significant impact on BCVA. Best-corrected visual acuity, older age, and lower number of yearly anti-VEGF injections are predictors for decrease BCVA.

A prodrome is an early set of signs or symptoms that indicate the onset of a disease before more typical symptoms develop. Prodromal stages are well recognized in some neurological and immune-mediated diseases such as Parkinson disease, schizophrenia, type 1 diabetes mellitus and rheumatoid arthritis. Emerging evidence indicates that a prodromal stage exists in multiple sclerosis (MS), raising the possibility of intervention at this stage to delay or prevent the development of classical MS. However, much remains unclear about the prodromal stage of MS and considerable research is needed to fully characterize the prodrome and develop standardized criteria to reliably identify individuals with prodromal MS who are at high risk of progressing to a diagnosis of MS. In this Roadmap, we draw on work in other diseases to propose a disease framework for MS that incorporates the prodromal stage, and set out key steps and considerations needed in future research to fully characterize the MS prodrome, identify early disease markers and develop standardized criteria that will enable reliable identification of individuals with prodromal MS, thereby facilitating trials of interventions to slow or stop progression beyond the prodrome.

To assess the number of recruits for military service in the Israeli Defense Force (IDF) who underwent refractive surgery prior to enlistment and examine whether the procedure affected their ability to accomplish combat training.Medical records of IDF recruits.Retrospective analysis of medical records of recruits with ametropia who underwent or did not undergo refractive surgery prior to enlistment.Recruits were categorized into ametropes and recruits who underwent refractive surgery. Fitness and assignment to combat units and completion status of combat training were compared between the two groups.The study included 334,688 (182,969 males, 151,719 females) ametropes of which 5231 (4753 males, 478 females) underwent refractive surgery prior to recruitment. Refractive surgery prevalence increased from 9/1000 ametropes in 2005 to 18.5/1000 ametropes in 2018 (r = 0.912, p 0.001); 2643 of the operated recruits (50.5%) had their surgery at the age of 17-18. Dropout rates from combat training were significantly lower in the refractive surgery group during the study period (1.68% vs. 6.14%, respectively, p 0.001). Soldiers in the operated group were more frequently referred to ophthalmologists than those in the ametropes group and less frequently referred to optometrists.The prevalence of refractive surgery in IDF recruits has increased substantially during the last decade with more of them applying to combat units. Refractive surgery opened new possibilities for recruits who were unfit for combat duty prior to surgery and did not appear to impair the chances of successfully completing combat training.

Urban Black men who have sex with men (MSM) bear a disproportionate burden of HIV and syphilis in the U.S. Experiences of enacted sexual minority stigma and psychological distress among these men may be associated with HIV/STI sexual and drug risk behaviors. The objective was to determine the associations between enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. In an urban prospective cohort study, survey measures assessed past 3-month exposure to enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. Multivariable logistic regression models were utilized for hypothesis testing. The Black MSM (N = 140) reported the following: 22.1% experiences of enacted sexual minority stigma, 39% high levels of psychological distress, 48.6% 1 sex partner, 8.6% transactional sex, and 6% injection drug use (IDU). In models adjusted for age and education, enacted sexual minority stigma significantly increased the odds of reporting 1 sex partner, transactional sex, and IDU. Adjusting additionally for homelessness, the association between enacted sexual minority stigma and transactional sex remained significant. Adding psychological distress to this model showed a significant association between psychological distress and transactional sex, while the association was no longer significant for transactional sex. These findings highlight some of the complex psycho-social relationships that may be associated with sexual and drug risk behaviors among Black MSM placing them at increased risk for HIV and syphilis.Hombres urbanos de raza Negra que tienen sexo con hombres (HSH) sobrellevan una carga desproporcionada de VIH y sífilis en los EE.UU. Experiencias de estigma efectivo de minoría sexual y angustia psicológica entre estos hombres pudiese ser asociado con conductas sexuales de riesgo VIH/ITS y drogas. El objetivo era determinar las asociaciones entre un estigma efectivo de minoría sexual, angustia psicológica, y comportamientos sexuales y de riesgo de drogas. En un estudio de cohortes prospectivo urbano, las medidas de la encuesta evaluada en los últimos tres meses de exposición al estigma efectivo, angustia psicológica, y sus conductas sexuales y comportamientos riesgoso de drogas. Modelos de regresión logística multivariante se utilizaron para la prueba de hipótesis. Los HSH de raza negra (N = 140) reportaron lo siguiente: 22.1% experiencias de estigma efectivo, 39% niveles altos de angustia psicológica, 48.6% y 1 pareja sexual, 8.6% sexo transaccional, y 6% uso de drogas inyectables (UDI). En modelos ajustados a edad y educación, un estigma efectivo de minoría sexual aumentó de manera significante las probabilidades de reportar y 1 pareja sexual, sexo transaccional, y UDI. Ajustando adicionalmente para personas sin vivienda, la asociación entre estigma efectivo de minoría sexual y sexo transaccional permaneció significante. La adición de angustia psicológica al modelo mostró una asociación significativa entre angustia psicológica y sexo transaccional, mientras que la asociación ya no era significativa para el sexo transaccional. Estos resultados destacan algunas de las complejas relaciones psicosociales que pudiesen estar asociadas con conductas sexuales y de riesgo de drogas entre HSH de raza negra, poniéndolos a mayor riesgo de contraer VIH y sífilis.

To evaluate the impact of postponed care attributed to coronavirus disease (COVID-19) pandemic lockdowns on visual acuity and the number of anti-VEGF injections in patients with retinal vein occlusion (RVO).A multicenter, retrospective study of consecutive RVO patients previously treated with anti-VEGF injections, which compared data from pre- (2019) and during (2020) COVID-19 lockdown period.A total of 814 RVO patients with a mean age of 72.8 years met the inclusion criteria. Of them, 439 patients were assessed in 2019 and 375 in 2020. There was no significant difference between the COVID-19 and pre-COVID-19 period in terms of baseline and final BCVA (p = 0.7 and 0.9 respectively), but there was a significantly reduced mean number of anti-VEGF injections during the COVID-19 period (5.0 and. 5.9 respectively, p 0.01), with a constant lower ratio of injections per patient. A noticeable decline was found during March-May (p 0.01) in 2020. Baseline BCVA (0.69, p 0.01) and the number of injections (- 0.01, p = 0.01) were predictors of final BCVA.In a large cohort of RVO patients, during 2020 lockdowns imposed due to the COVID-19 pandemic, a significant reduction in the annual number of anti-VEGF injections was noted. The postponed care did not result in a significant impact on the final BCVA. Baseline BCVA and the number of annual injections serve as predictors for final BCVA in RVO patients.

Although human trafficking is recognized as a public health issue, research on the health effects of human trafficking and best intervention practices is limited. We describe 2 citywide collaborative victim services models, the THRIVE (Trafficking, Healthcare, Resources, and Interdisciplinary Victim Services and Education) Clinic at the University of Miami and Jackson Health System in Miami, Florida, and the Greater Houston Area Pathways for Advocacy-based, Trauma-Informed Healthcare (PATH) Collaborative at Baylor College of Medicine, CommonSpirit Health, and San Jose Clinic in Houston, Texas, funded in part by the Office for Victims of Crime, which focus on trauma-informed health care delivery for victims of human trafficking. From June 2015 through September 2021, the THRIVE Clinic served 214 patients with an average age of 28.7 years at the time of their first visit. From October 2017 through September 2021, the PATH Collaborative received 560 suspected trafficking referrals, 400 of which screened positive for labor or sex trafficking. These models serve as a framework for replication of interdisciplinary practices to provide health care for this unique population and preliminary information about the strategies put in place to assist victims during their recovery. Key lessons include the importance of a citywide needs assessment, patient navigators, interdisciplinary care, and building community partnerships to ensure safe housing, transportation, identification, health insurance, vocation services, input from survivors, peer-to-peer mentorship, and medical–legal services. Further research is needed to understand the detrimental health effects of trafficking and the health care needs of victims. In addition, a need exists to develop optimal models of care for recovery and reintegration for this patient population and to address public health, legal, and medical policies to ensure access to and sustainability of comprehensive, trauma-informed, interdisciplinary victim services.

OBJECTIVES: The metabolic abnormalities that lead to diabetes mellitus (DM) following an episode of acute pancreatitis (AP) have not been extensively studied. This manuscript describes the objectives, hypotheses, and methods of mechanistic studies of glucose metabolism that comprise secondary outcomes of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) Study. METHODS: Three months after an index episode of AP, participants without pre-existing DM will undergo baseline testing with an oral glucose tolerance test. Participants will be followed longitudinally in three sub-cohorts with distinct metabolic tests. In the first and largest subcohort, oral glucose tolerance tests will be repeated 12 months after AP and annually to assess changes in β-cell function, insulin secretion, and insulin sensitivity. In the second, mixed meal tolerance tests will be performed at 3 and 12 months, then annually, and following incident DM to assess incretin and pancreatic polypeptide responses. In the third, frequently-sampled intravenous glucose tolerance tests will be performed at 3 months and 12 months to assess the first-phase insulin response and more precisely measure β-cell function and insulin sensitivity. CONCLUSIONS: The DREAM study will comprehensively assess the metabolic and endocrine changes that precede and lead to the development of DM after AP.

Transcatheter electrosurgery is a versatile tool that can be used to cut cardiac tissue without the need for a sternotomy, cardiopulmonary bypass, and cardioplegia. With adequate imaging and suitable anatomy, any cardiac tissue can be cut. Thus, transcatheter electrosurgery can provide bespoke therapies for complex patients who often have no other good treatment options. In this review, we will discuss the common applications for electrosurgical tissue traversal and laceration, including transcaval access, BASILICA, LAMPOON, and ELASTA-Clip, summarizing the evidence and the key technical steps for each.

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM following AP and understanding the underlying mechanisms. The Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM following AP. In the following article, we summarize literature regarding the epidemiology of DM following AP, and provide the rationale and an overview of the DREAM study.

Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1's pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.