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The Hurst exponent (H) isolated in fractal analyses of neuroimaging time-series is implicated broadly in cognition. Within this literature, H is associated with multiple mental disorders, suggesting that H is transdimensionally associated with psychopathology. Here, we unify these results and demonstrate a pattern of decreased H with increased general psychopathology and attention-deficit/hyperactivity factor scores during a working memory task in 1,839 children. This pattern predicts current and future cognitive performance in children and some psychopathology in 703 adults. This pattern also defines psychological and functional axes associating psychopathology with an imbalance in resource allocation between fronto-parietal and sensory-motor regions, driven by reduced resource allocation to fronto-parietal regions. This suggests the hypothesis that impaired working memory function in psychopathology follows from a reduced cognitive resource pool and a reduction in resources allocated to the task at hand.

OBJECTIVE Return-to-learn (RTL) after sport-related concussion (SRC) is an important yet understudied topic. The authors sought to do the following: 1) describe patterns of RTL among athletes by school level (i.e., middle school, high school, college); and 2) evaluate the predictive value of school level on RTL duration. METHODS A retrospective, single-institution cohort study of adolescent and young adult athletes 12–23 years old who sustained an SRC between November 2017 and April 2022 and who presented to a multidisciplinary specialty concussion clinic was conducted. The independent variable was school level, trichotomized into middle school, high school, and college. Time to RTL was the primary outcome and was defined as days from SRC to return to any academic activities. ANOVA was used to compare RTL duration across school levels. A multivariable linear regression was performed to evaluate for predictive value of school level on RTL duration. Covariates included the following: sex, race/ethnicity, learning disorder, psychiatric conditions, migraines, family history of psychiatric conditions/migraines, initial Post-Concussion Symptom Scale score, and number of prior concussions. RESULTS Of 1007 total athletes, 116 (11.5%) were in middle school, 835 (83.0%) were in high school, and 56 (5.6%) were in college. The mean RTL times (in days) were as follows: 8.0 ± 13.1 (middle school), 8.5 ± 13.7 (high school), and 15.6 ± 22.3 (college). One-way ANOVA showed a statistically significant difference between groups (F[2, 1007] = 6.93, p = 0.001). A Tukey post hoc test revealed a longer RTL duration in collegiate athletes when compared to middle school (p = 0.003) and high school (p < 0.001) athletes. Collegiate athletes had longer RTL duration compared to other school levels (β = 0.14, p < 0.001). There was no difference between middle school and high school athletes (p = 0.935). The subanalysis revealed a longer RTL duration in high school freshmen/sophomores (9.5 ± 14.9 days) when compared to juniors/seniors (7.6 ± 12.6 days; t = 2.05, p = 0.041), and being an older (junior/senior) high school athlete was predictive of shorter RTL duration (β = −0.11, p = 0.011). CONCLUSIONS When examining patients who presented to a multidisciplinary sport concussion center, RTL duration was longer in collegiate athletes when compared to middle and high school athletes. Younger high school athletes had longer time to RTL compared to their older counterparts. This study provides insight into how varying scholastic environments may contribute to RTL.

Interest and participation in competitive Martial Arts such as Taekwondo, Karate, Kung Fu, Aikido, and Tai Chi is growing in children, adolescent as well as in adults in the USA and worldwide. Competitive Martial Arts require daily training weeks and sometimes, months prior to the start of a competition or tournament. The training period could be for a few hours daily over a period of one to six months with one or two days for every one week for rest and recovery. The types and extents of injuries after competition depend upon the form of Martial Arts and the type of physical contact. They include muscle, joint, head and neck, groin, upper and lower extremities, and soft tissues. Some acute injuries can be taken care of at home and the injured may recover quickly. Some injuries may require hospitalization and even surgery; while others may take longer period to recover and require stoppage in training. The training involves daily exercises during which moderate levels of reactive oxygen species (ROS) are produced. ROS activates a transcriptional factor Nrf2 (nuclear factor-erythroid 2-related factor 2) which enhances the levels of antioxidant enzymes; and thereby, reduces oxidative stress. Because of this observation, some investigators have suggested that supplementation with micronutrient and antioxidant compounds is not necessary for reducing injuries and improving the rate of healing from injury. Appropriate diet recommended for Martial Arts athletes are sufficient to reduce oxidative damage and protect against injuries that occur during Martial Arts competitions. The use of a single antioxidant in reducing oxidative stress has produced inconsistent results in reducing the markers of oxidative stress. The limitations of such an approach are briefly discussed. This review has proposed a mixture of micronutrients which may reduce oxidative stress and improve performance in Martial Arts competitions. In addition, some beneficial effects of Martial Arts are also described.&nbsp

In recognition, context effects often manifest as higher hit and false-alarm rates to probes tested in an old context compared with probes tested in a new context; sometimes, this concordant effect is accompanied by a discrimination advantage. According to the cue-overload account of context effects (Rutherford, 2004), context acts like any other cue, and thus context effects should be larger with lighter context loads. Conversely, the Item, Associated Context, and Ensemble (ICE) account (Murnane et al., 1999) attributes context effects to two factors: subjects erroneously attributing context familiarity to the probe, and the formation of ensembles (mnemonic combinations of item and context). Context familiarity increases as exposure at study increases, and thus ICE predicts larger effects of context as context load increases. Relatedly, ICE predicts larger effects of context as context meaningfulness increases, as meaningful contexts are more likely to be bound to the target in an ensemble. In Experiments 1 and 2, rather than manipulate context load during the study phase, we relied on subjects' preexperimental context exposure to manipulate context load. Subjects studied words superimposed on photographs of their university campus or another university campus. At test, targets and distractors were evenly divided between study and novel contexts and between familiar and unfamiliar contexts. In Experiment 3, we manipulated context familiarity within the experimental session. Results supported ICE, suggesting that context does not act as a retrieval cue in recognition. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. Methods 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−). Results We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Conclusions Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

Photosynthetic organisms frequently experience abiotic stress that restricts their growth and development. Under such circumstances, most absorbed solar energy cannot be used for CO2 fixation and can cause the photoproduction of reactive oxygen species (ROS) that can damage the photosynthetic reaction centers of PSI and PSII, resulting in a decline in primary productivity. This work describes a biological “switch” in the green alga Chlamydomonas reinhardtii that reversibly restricts photosynthetic electron transport (PET) at the cytochrome b6f (Cyt b6f) complex when the capacity for accepting electrons downstream of PSI is severely limited. We specifically show this restriction in STARCHLESS6 (sta6) mutant cells, which cannot synthesize starch when they are limited for nitrogen (growth inhibition) and subjected to a dark-to-light transition. This restriction represents a form of photosynthetic control that causes diminished electron flow to PSI and thereby prevents PSI photodamage but does not appear to rely on a ΔpH. Furthermore, when electron flow is restricted, the plastid alternative oxidase (PTOX) becomes active, functioning as an electron valve that dissipates some excitation energy absorbed by PSII and allows the formation of a proton motive force (PMF) that would drive some ATP production (potentially sustaining PSII repair and nonphotochemical quenching [NPQ]). The restriction at the Cyt b6f complex can be gradually relieved with continued illumination. This study provides insights into how PET responds to a marked reduction in availability of downstream electron acceptors and the protective mechanisms involved.

Salt marshes are globally important ecosystems, but many have been lost or transformed due to the impacts of global change. There have been attempts to broadly quantify salt marsh communities, especially the ubiquitous grasses which serve as foundation species such as Spartina alterniflora and Spartina patens, the latter of which is being lost due to sea level rise. However, few researchers have used high-resolution geospatial imagery to quantify fine-scale changes in the distribution of grasses or to track losses of S. patens. To address this issue, we utilized a simple and rapid method of classifying geospatial marsh imagery with cloud-based machine learning in Google Earth Engine (>92% accuracy for S. patens regardless of imagery age). Our methods allowed us to characterize full landscapes (two geospatially proximal areas, >7,000 ha each) of critical salt marshes on the New Jersey coast and to evaluate fine-scale (1-m) community transformations in response to global change with imagery from 2006 to 2019. Notably, one marsh experienced very little change while the other experienced an 81.17% (1,087 ha) loss of S. patens, illuminating disparate patterns of change for two geographically proximal ecosystems. Further exploration revealed an association in the loss of S. patens with increases in streamflow and total nitrogen content in the rivers that run through each marsh. These results signify the importance of broad-scale ecological studies that evaluate fine-scale community transformations and for management strategies that do not generalize across landscapes of an ecosystem-type.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Prostate cancer (PCa) is a leading cause of death and partially heritable. Genetic risk prediction might be useful for strategies to reduce PCa mortality through early detection and prevention.To review evidence for genetic risk prediction for PCa.A collaborative literature review was conducted using PubMed and Google Scholar. Search terms included genetic, risk, prediction, and "prostate cancer". Articles addressing screening, early detection, or prevention were prioritized, as were studies involving diverse populations.Rare pathogenic mutations (RPMs), especially in DNA damage repair genes, increase PCa risk. RPMs in BRCA2 are most clearly deleterious, conferring 2-8.6 times higher risk of PCa and a higher risk of aggressive disease. Common genetic variants can be combined into genetic risk scores (GRSs). A high GRS (top 20-25% of the population) confers two to three times higher risk of PCa than average; a very high GRS (top 1-5%) confers six to eight times higher risk. GRSs are not specific for aggressive PCa, possibly due to methodological limitations and/or a field effect of an elevated risk for both low- and high-grade PCa. It is challenging to disentangle genetics from structural racism and social determinants of health to understand PCa racial disparities. GRSs are independently associated with a lethal PCa risk after accounting for family history and race/ancestry. Healthy lifestyle might partially mitigate the risk of lethal PCa.Genetic risk assessment is becoming more common; implementation studies are needed to understand the implications and to avoid exacerbating healthcare disparities. Men with a high genetic risk of PCa can reasonably be encouraged to adhere to a healthy lifestyle.Prostate cancer risk is inherited through rare mutations and through the combination of hundreds of common genetic markers. Some men with a high genetic risk (especially BRCA2 mutations) likely benefit from early screening for prostate cancer. The risk of lethal prostate cancer can be reduced through a healthy lifestyle.

To describe endotracheal intubation practices in emergency departments by staff intubating patients early in the coronavirus disease 2019 (COVID-19) pandemic.Multicenter prospective cohort study of endotracheal intubations conducted at 20 US academic emergency departments from May to December 2020, stratified by known or suspected COVID-19 status. We used multivariable regression to measure the association between intubation strategy, COVID-19 known or suspected status, first-pass success, and adverse events.There were 3,435 unique emergency department endotracheal intubations by 586 participating physicians or advanced practice providers; 565 (18%) patients were known or suspected of having COVID-19 at the time of endotracheal intubation. Compared with patients not known or suspected of COVID-19, endotracheal intubations of patients with known or suspected COVID-19 were more often performed using video laryngoscopy (88% versus 82%, difference 6.3%; 95% confidence interval [CI], 3.0% to 9.6%) and passive nasal oxygenation (44% versus 39%, difference 5.1%; 95% CI, 0.9% to 9.3%). First-pass success was not different between those who were and were not known or suspected of COVID-19 (87% versus 86%, difference 0.6%; 95% CI, -2.4% to 3.6%). Adjusting for patient characteristics and procedure factors in those with low anticipated airway difficulty (n=2,374), adverse events (most commonly hypoxia) occurred more frequently in patients with known or suspected COVID-19 (35% versus 19%, adjusted odds ratio 2.4; 95% CI, 1.7 to 3.3).Compared with patients not known or suspected of COVID-19, endotracheal intubation of those confirmed or suspected to have COVID-19 was associated with a similar first-pass intubation success rate but higher risk-adjusted adverse events.

BackgroundMultiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs).ObjectiveTo evaluate RSIrs for automated patient-level detection of csPCa.Design setting and participantsWe retrospectively studied all patients (n=151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI.InterventionWe calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records.Outcome measurements and statistical analysisWe compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α=0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones.Results and limitationsAUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p&nbsp

Adalimumab is the only FDA-approved biologic for hidradenitis suppurativa (HS). In the setting of increasing obesity rates worldwide, the relationship between adalimumab efficacy for HS and BMI is essential to understand. We assessed this relationship through markers of disease severity and inflammation.Institutional review board-approved retrospective chart review of Montefiore/Einstein HS Center (HSC) patients (n = 57) treated with adalimumab. The relationship between BMI and adalimumab efficacy was assessed through disease severity (HS-Physician Global Assessment [HS-PGA] 0 and Numerical Rating Scale Pain [NRS-Pain]) and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and interleukin-6 [IL-6]). A BMI ≥ 30 is defined as obese; BMI 30 is defined as non-obese.The mean age was 35.8 ± 13.0 years. After adalimumab therapy, those with BMI 30 experienced significant reductions in HS-PGA (-1.5 ± 0.9; P 0.0001) and NRS-Pain (-1.6 ± 2.1; P 0.0001), as well as mean decreases in inflammatory markers ESR, CRP, and IL-6 (-17.90 ± 23.6, -0.71 ± 1.4, -5.88 ± 7.9, respectively; P 0.05). Obese patients (BMI ≥ 30) experienced mean increases in HS-PGA (+0.22 ± 0.8; P 0.05) and NRS-Pain scores (+1.41 ± 3.5; P 0.05) as well as mean increases in ESR, CRP, and IL-6 (+2.62 ± 28.3, +0.44 ± 3.0, +2.35 ± 6.9, respectively; P 0.05). Comparing the cohorts, differences in changes in HS-PGA, NRS-Pain, ESR, and IL-6 after therapy are significantly different (P 0.05).We identified significantly lower efficacy of adalimumab in HS patients with BMI ≥ 30 compared to those with BMI 30. Those with BMI ≥ 30 demonstrated signs of both clinical and physiological deterioration while on adalimumab. Future studies are needed to examine adalimumab dosing for HS patients with high BMI, as well as a critical reconsideration of weight-based therapies.

Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients.A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma).Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040).These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

The 2022 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Exploring New Frontiers in Prostate Cancer Research," was held from June 23 to 26, 2022, at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.The CHPCA Meeting is an annual discussion-oriented scientific conference organized by the Prostate Cancer Foundation, that focuses on emerging and next-step topics deemed critical for making the next major advances in prostate cancer research and clinical care. The 2022 CHPCA Meeting included 35 talks over 10 sessions and was attended by 73 academic investigators.Major topic areas discussed at the meeting included: prostate cancer diversity and disparities, the impact of social determinants on research and patient outcomes, leveraging real-world and retrospective data, development of artificial intelligence biomarkers, androgen receptor (AR) signaling biology and new strategies for targeting AR, features of homologous recombination deficient prostate cancer, and future directions in immunotherapy and nuclear theranostics.This article summarizes the scientific presentations from the 2022 CHPCA Meeting, with the goal that dissemination of this knowledge will contribute to furthering global prostate cancer research efforts.

Many of the diseases that plague society today are driven by a loss of protein quality. One method to quantify protein quality is to measure the protein folding stability (PFS). Here, we present a novel mass spectrometry (MS)-based approach for PFS measurement, iodination protein stability assay (IPSA). IPSA quantifies the PFS by tracking the surface-accessibility differences of tyrosine, histidine, methionine, and cysteine under denaturing conditions. Relative to current methods, IPSA increases protein coverage and granularity to track the PFS changes of a protein along its sequence. To our knowledge, this study is the first time the PFS of human serum proteins has been measured in the context of the blood serum (in situ). We show that IPSA can quantify the PFS differences between different transferrin iron-binding states in near

Burnout among physicians is a syndrome of emotional exhaustion, de-personalization, and reduced sense of personal accomplishment that can negatively affect personal relationships, physician well-being, and patient outcomes. Although burnout rates of up to 50% to 60% among orthopedic surgeons have been reported, no studies have evaluated burnout among orthopedic generalists and subspecialists. The primary goal of this study was to examine the prevalence of burnout among orthopedic disciplines. We conducted a multicenter study from March 2019 through December 2019 involving 149 orthopedists. An abbreviated Maslach Burnout Inventory-Human Services Survey was used to measure burnout. Demographic information, personal characteristics, professional characteristics, family life and spousal support, and depression were also assessed. The mean rate of burnout among all respondents was 62%, whereas 16.77% screened positive for depression. Subspecialties with the highest rates of burnout were oncology (100%), sports medicine (68%), and trauma (63%). Similarly, trauma (50.00%), oncology (40.00%), and general orthopedics (20.00%) had the highest positive depression screening rates. In contrast, shoulder and elbow (50%), pediatric (52%), and foot and ankle (54%) specialists had the lowest rates of burnout, whereas shoulder and elbow (0.00%), spine (0.00%), and sports medicine (6.50%) specialists had the lowest rates of positive depression screening. Older age, higher debt load, and oncology subspecialty were associated with increased burnout risk. This study sought to determine burnout rates within each orthopedic discipline, with a secondary aim of disclosing contributing factors. Trauma and oncology had the highest rates of burnout and positive depression screening. Because this study represents a small orthopedic cohort, larger studies are needed to appropriately manage burnout in the future. [ Orthopedics . 2022;45(6):333–339.]

Background Genetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group. Methods This was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021. Cox proportional hazards analyses tested for association of genetic and other risk factors (including self-reported race and ethnicity and family history) with age at death from prostate cancer, age at diagnosis of metastatic (nodal or distant) prostate cancer, and age at diagnosis of any prostate cancer. Results A total of 590 750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (P Conclusions PHS290 stratified US veterans of diverse ancestry for lifetime risk of prostate cancer, including metastatic and fatal cancer. Predicting genetic risk of lethal prostate cancer with PHS290 might inform individualized decisions about prostate cancer screening.

We assess the composition and geometry of four individual rock glaciers in Alaska, Wyoming and Colorado by measuring their radio wave speed and applying these results to ground-penetrating radar depth corrections and dielectric mixing models. Our method includes a correction for subsurface reflector dip angle, which we show can lead to an incorrect determination of wave speeds using common midpoint configurations. By observing the radar properties of the rock glaciers and their supraglacial debris, we find that some of the sites exhibit nearly pure ice cores, and all of the sites indicate volumetric ice fractions >50%. These results have implications for terrestrial glaciology and hydrology because the present ice volume is connected to past ice accumulation and subsurface ice preservation, which may affect the future availability of alpine water resources. An understanding of the processes that govern rock glacier evolution over a wide range of latitudes and elevations will also contribute to the exploration of planetary surfaces such as Mars, which hosts a significant population of debris-covered glaciers. Our subsurface composition and geometry estimates will inform simulations of rock glacier formation and evolution to test hypothesized ice origin mechanisms along with the preservation of climate signals.

Current dogma dictates that, during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS transcription factors (TFs), ERG and Fli1. Although deletion of either ERG or Fli1 manifests subtle vascular dysfunction, their combined genetic deletion in adult ECs results in acute vasculopathy and multi-organ failure, due to loss of EC fate and integrity, hyperinflammation and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency causes rapid transcriptional silencing of pan and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality, enabling in vivo engraftment of a perfusable vascular network. Genome-wide association study analysis identified vascular diseases that are associated with FLI1/ERG mutations. Constitutive expression of ERG and Fli1 upholds EC fate, physiological function and resilience in adult vasculature, whereas their functional loss can contribute to systemic human diseases.

Hematopoietic stem cells (HSCs) with age-associated somatic mutations that disproportionally contribute to hematopoiesis generate the condition known as clonal hematopoiesis (CH). While CH conveys increased risk of hematologic cancer, there is also strong association between CH and cardiovascular disease (CVD). Accumulating evidence suggests that inflammation mechanistically links CH to CVD, and we hypothesized that CH may be a predictive biomarker of CVD in conditions of chronic inflammation. One such patient population comprises people living with HIV (PLWH) who also have substantially increased incidences of CVD and CH . We studied the association between CH and CVD in PLWH using samples from ACTG Study A5001 (or ALLRT), a prospective clinical trial of HIV-infected persons with long-term follow-up. We observed a positive association between CH and CVD in PLWH independent of traditional CVD risk factors. Moreover, in CVD cases, the CH clone was identifiable in the blood years before CVD diagnosis, unlike in PLWH with CH who did not have CVD. With the life span of PLWH increasing because of advances in treatment, our results indicate that the presence of CH and its clonal dynamics could be used as a prognostic biomarker of the risk for CVD in PLWH.

Thousands of orthopedic surgeons in the United State face medical malpractice claims annually; however, little is known regarding the common causes for litigation against shoulder surgeons. In addition, the current analysis does not take into consideration how surgical frequency affects the litigation likelihood. The purpose of our investigation was to identify the most common causes of litigation against shoulder surgeons in the United States adjusting for surgical frequency.The VerdictSearch database was used using the search terms "medical malpractice," "shoulder," and "NOT cancer." Results were queried, and all studies pertaining to orthopedic shoulder surgery included. Data gathered included cause of lawsuit, indemnity paid, type of surgery performed, results of the cases, verdict or settlement, and, if applicable, technical error. A query of a multisurgeon institutional database was conducted to determine how frequently surgeries were performed. Then the frequency of litigation was adjusted by the procedure frequency to determine which surgery has the greatest likelihood to be litigated relative to rotator cuff surgery.Forty-five cases were included in our study. After adjusting for the procedure frequency, the most likely procedure to be litigated, relative to rotator cuff repair, was manipulation under anesthesia (MUA), 251 times more likely to be litigated, and washout/lavage procedures, 17 times more likely to be litigated. Injection and total shoulder arthroplasty were 23 and 14 times less likely to be litigated relative to rotator cuff repair, respectively. In addition, the average age of the patients was 47 years, and 53% of the cases involved a male plaintiff. The most commonly litigated procedures were rotator cuff repair (42%), MUA (13%), and humeral open reduction and internal fixation (9%). The most commonly cited symptoms for litigation against shoulder surgeons were pain (60%) and loss of range of motion (40%). Of the 45 cases, 44% ended in physician loss, with the average indemnity paid via verdict being $1,118,714 vs. $416,875 for settlement.This study identifies that MUA and lavage/washout procedures are much more likely to be litigated relative to rotator cuff repair. Rotator cuff repair is actually one of the least likely procedures to be litigated. Furthermore, settlement may represent a method of decreasing the indemnity paid for malpractice cases for which surgeons are implicated.

Global South scholars have long documented and theorised their communities’ struggles against the ecological degradation, toxic contamination, and climate change–related extreme weather events which result from the overlapping ills of colonialism, imperialism, and racial capitalism. Building on that existing work, contributors to this collection extend and deepen understandings of the material entanglements of race and ecology in our contemporary conjuncture. Speaking from various scales and locations, including the Caribbean, Brazil, Sri Lanka, and Palestine, the authors reflect on those sites while also collectively recovering and amplifying lineages of thought on ecology from across the South. As the contributions collected here show, the traps set by global structures of race also direct mainstream climate solutions back towards the expropriation, premature death, or prevention of birth of peoples of colour by various means, from militarised conservation to eugenic populationism. Confronting the racial logics of both ecological harm and its supposed solutions is therefore a key task of this collection. As a collective, however, the issue’s contributors also carve out paths to reparation and structural change which form the contours of an anti-racist ecology for our times. Publisher PDF

The N-nitroso-trischloroethylurea (NTCU)-induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32 weeks. NTCU induces the appearance of basal cells in murine airways while decreasing/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. Hamp;E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU-exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPARγ agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.

To estimate the changes in infertility from 1995-2019 and determine the association of individual-level characteristics with fertility in the United States.Cross-sectional study.Periodic data from 1995, 2002, 2006-2010, 2011-2013, 2013-2015, 2015-2017, and 2017-2019 cycles of the National Survey for Family Growth were used for this analysis. The National Survey for Family Growth comprises samples of the household-level population of women aged 15-44 years in the United States.Surveyed married and cohabiting women aged 15-44 years.None.The primary outcomes were the rates of infertility across subgroups of married or cohabiting women. For secondary outcomes, we performed bivariable and multivariable logistic regression models using the pooled sample (N = 53,764) to determine the association of individual-level characteristics, including age, parity, pelvic inflammatory disease treatment, education, income, race or ethnicity, and receipt of sexual and reproductive health services, with the odds of 12-month infertility among married or cohabiting women.The fluctuations in infertility over this period, with a low of 5.8% in 2006-2010 and a high of 8.1% in 2017-2019, were not found to be statistically significant. This trend was present across nearly all subgroups. The multivariable model showed that women who were older and nulliparous, had fewer years of education, had lower income, were non-Hispanic black, or were not receiving sexual and reproductive health services were more likely to be infertile.This study confirms that parity, age, race, and education level continue to have an association with infertility. Further, the results demonstrate that access to sexual and reproductive health services plays an important role in infertility. In contrast to previous studies, infertility in the United States is no longer on the decline, and Hispanic ethnicity did not have a significant relationship with infertility. Given the rise of sexually transmitted infections and the persistent lack of access to sexual and reproductive health services, particularly among already vulnerable groups, the connection between access to care and infertility is ripe for further investigation.

OBJECTIVE: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia—signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume—could be replicated in an independent schizophrenia sample, and investigated whether expression of these signatures can be detected at the population level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. METHODS: This cross-sectional study used an independent schizophrenia-control sample (N=347; ages 16–57 years) for replication of imaging signatures, and then examined two independent population-level data sets: typically developing youths and youths with psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort (N=359; ages 16–23 years) and adults in the UK Biobank study (N=836; ages 44–50 years). The authors quantified signature expression using support-vector machine learning and compared cognition, psychopathology, and polygenic risk between signatures. RESULTS: Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youths with psychosis spectrum symptoms than in typically developing youths, whereas signature 2 frequency was similar in the two groups. In both youths and adults, signature 1 was associated with worse cognitive performance than signature 2. Compared with adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. CONCLUSIONS: The authors successfully replicated two neuroanatomical signatures of schizophrenia and describe their prevalence in population-based samples of youths and adults. They further demonstrated distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

Human immunodeficiency virus (HIV) infection is prevalent among children and adolescents in Botswana, but standardized neurocognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) attempts to streamline evaluation of neurocognitive functioning and has been culturally adapted for use among youth in this high-burden, low-resource setting. However, its reliability across measurements (i.e., test–retest reliability) is unknown. This study examined the test–retest reliability of the culturally adapted PennCNB in 65 school-age children (age 7–17) living with HIV in Botswana. Intraclass correlation coefficients (ICCs) for PennCNB summary scores (ICCs > 0.80) and domain scores (ICCs = 0.66–0.88) were higher than those for individual tests, which exhibited more variability (ICCs = 0.50–0.82), with the lowest reliability on memory tests. Practice effects were apparent on some measures, especially within memory and complex cognition domains. Taken together, the adapted PennCNB exhibited adequate test–retest reliability at the domain level but variable reliability for individual tests. Differences in reliability should be considered in implementation of these tests.

Suicide is a major, preventable public health problem. The general factor of psychopathology ("p" factor) might help improve detection and prediction of individuals at risk for suicide. This cross-sectional proof-of-concept study tests whether the p-factor score is associated with suicidal thoughts and behaviors (STB) better than a depression scale alone. Youth (N = 841; mean age 18.02

Validated screening tools are needed to detect subtle cognitive impairment in individuals at-risk for developing psychosis. Here, the utility of the Mini-Mental Status Examination (MMSE) and Penn Computerized Neurocognitive Battery (CNB) were evaluated for detecting cognitive impairment in individuals with psychosis spectrum (PS) symptoms.Participants (n = 229; 54 % female) completed the MMSE and CNB at baseline and two-year follow-up. PS (n = 91) and typically developing (TD; n = 138) participants were enrolled at baseline based on the presence or absence of PS symptoms. After two years, 65 participants remained PS, 104 participants remained TD, 23 participants had Emergent (EP) subthreshold PS symptoms, and 37 participants were experiencing Other Psychopathology (OP).Generally, those with PS had lower scores than TD on both the MMSE (p 0.0001) and CNB (p 0.0001). Additionally, OP participants performed lower on the MMSE than TD (p = 0.02). Receiver operating characteristic (ROC) analyses indicated similar area under the curve (AUCs) for the two instruments (0.67); the MMSE showed higher specificity (0.71 vs. 0.62), while the CNB showed higher sensitivity (0.66 vs 0.52). Use of the MMSE and CNB in combination provided the highest diagnostic classification.The MMSE and CNB can be used to screen for cognitive impairment in PS. The MMSE is better at ruling out PS-related cognitive impairment while the CNB is better at ruling in PS-related cognitive impairment. Overall, our results indicate that both tests are useful in screening for cognitive impairment, particularly in combination, in a PS population.

We released nearly 1.0 million 1-day post-hatch (dph) and 5-dph pallid sturgeon (Scaphirhynchus albus) free embryos in the Missouri River on 1 July 2019 and sequentially captured survivors at multiple sites through a 240-km river reach to quantify daily growth and survival rates during the early life stages. Genetic analysis was used to assign captured fish to released family lots and known ages. Growth rate was similar (0.74–0.75 mm day−1) between the 1- and 5-dph age groups during the 3–4-day dispersal period when water temperature averaged 16.8 °C. Daily survival rate was 0.64 during 1–4 dph for the original 1-dph age group and 0.80 during 5–7 dph for the original 5-dph age group. Total survival during free embryo dispersal (hatch to 9 dph) was estimated as 0.0437. The transition from dispersing as free embryos to settling as benthic larvae was verified for fish originally released as 5 dph. Growth of settled larvae was quantified with a Gompertz model through 75 dph (9 September; 112 mm) when water temperature was 18.8–21.0 °C in the rearing areas. Settled larvae had an estimated daily survival rate of 0.96, and estimated total survival during 9–75 dph was 0.0714. This study provides the first empirical survival estimates for pallid sturgeon early life stages in natural settings and is one of few studies reporting similar information for other sturgeon species. Applications of this work extend to pallid sturgeon restoration programs where population models are being developed to predict recruitment potential and population responses to river management alternatives.

A polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) has been found to be associated with ADHD in multiple studies, but also with many other dimensions of problems. Little is known, however, about the processes underlying these transdiagnostic associations. Using data from the baseline and 1-year follow-up assessments of 9- to 10-year-old children in the Adolescent Brain Cognitive Development™ (ABCD©) Study, associations were assessed between an ADHD PRS and both general and specific factors of psychological problems defined in bifactor modeling. Additionally, prospective mediated paths were tested from the ADHD PRS to dimensions of problems in the follow-up assessment through baseline measures of executive functioning (EF) and two facets of impulsivity: lower perseverance and greater impulsiveness in the presence of surgent positive emotions. Previous findings of modest but significant direct associations of the ADHD PRS with the general factor of psychological problems were replicated in both assessments in 4,483 children of European ancestry. In addition, significant statistical mediation was found from the ADHD PRS to the general factor, specific ADHD, and conduct problems in the follow-up assessment through each of the two facets of impulsivity. In contrast, EF did not statistically mediate associations between the ADHD PRS and psychological problems. These results suggest that polygenic risk transdiagnostically influences both psychological problems and facets of impulsivity, perhaps partly through indirect pathways via facets of impulsivity.