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Colonization plays an important role during assembly of the gut microbiome and influences microbiome composition throughout the life of the host, but determinants of colonization success are not yet fully understood. The size of introduced populations and frequency of their introduction can be important drivers of colonization success for introduced species. However, the effect of these factors, which are known together as “propagule pressure,” varies across environments and can be modulated by the strength of competition between introduced and resident species. In vitro microbial communities provide a tractable, high-throughput experimental system to interrogate the influence of propagule pressure on colonization. To quantify the importance of propagule size during colonization in gut microbial communities, we derived in vitro communities from human stool samples and systematically mixed eight pairs of communities at seven ratios ranging from 1:1000 to 1000:1. We compared our results to the predictions of a neutral model in which the relative abundance of each species remains proportional to its inoculation dose, a measure of propagule size. We observed that community co-cultures maintained similar levels of species diversity to the parent communities regardless of mixture ratio, suggesting that community diversity may be limited by resource competition even when many species are initially present. Likewise, community composition was generally maintained across mixture ratios, in contrast to neutral predictions. However, certain bacterial taxa showed varying levels of dose-dependence across mixtures, suggesting that the effect of propagule size depends on community composition and may be affected by the strength of competitive interactions in each mixture. Our results highlight the importance of both propagule pressure and competition in determining colonization success in gut microbial communities.

Background: Adult hypertension is a well-established risk factor for stroke in young adults (aged Methods: A nationwide, retrospective cohort study of adolescents (aged 16–19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status. Results: The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38–47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5–3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3–3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2–3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings. Conclusions: Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.

AimsThe aim of this study was to assess the accuracy of pedicle screw placement, as well as intraoperative factors, radiation exposure, and complication rates in adult patients with degenerative disorders of the thoracic and lumbar spines who have undergone robotic-navigated spinal surgery using a contemporary system.MethodsThe authors reviewed the prospectively collected data on 196 adult patients who had pedicle screws implanted with robot-navigated assistance (RNA) using the Mazor X Stealth system between June 2019 and March 2022. Pedicle screws were implanted by one experienced spinal surgeon after completion of a learning period. The accuracy of pedicle screw placement was determined using intraoperative 3D fluoroscopy.ResultsA total of 1,123 pedicle screws were implanted: 1,001 screws (89%) were placed robotically, 63 (6%) were converted from robotic placement to a freehand technique, and 59 (5%) were planned to be implanted freehand. Of the robotically placed screws, 942 screws (94%) were determined to be Gertzbein and Robbins grade A with median deviation of 0.8 mm (interquartile range 0.4 to 1.6). Skive events were noted with 20 pedicle screws (1.8%). No adverse clinical sequelae were noted in the 90-day follow-up. The mean fluoroscopic exposure per screw was 4.9 seconds (SD 3.8).ConclusionRNA is highly accurate and reliable, with a low rate of abandonment once mastered. No adverse clinical sequelae occurred after implanting a large series of pedicle screws using the latest generation of RNA. Understanding of patient-specific anatomical features and the real-time intraoperative identification of risk factors for suboptimal screw placement have the potential to improve accuracy further.Cite this article: Bone Joint J 2023;105-B(5):543–550.

Purpose: Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion–mediated osimertinib resistance has not previously been published. Patients and Methods: Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected. Results: Fourteen patients with EGFR-mutant and RET fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%–75%, n = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4–ALK/STRN–ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms. Conclusions: For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination.

El principal objetivo de este trabajo es observar y analizar los cambios y continuidades vinculados a la forma y estructura de las campañas electorales en Argentina durante el período 1973-1983. En segundo lugar, enmarcar los alcances de las transformaciones ocurridas tanto a nivel general como intrapartidario. Fundamental para la modernización de la comunicación política en el país, la década antes mencionada, presentó grandes particularidades: inestabilidad democrática, crisis de liderazgo -causada por la muerte de dos importantes referentes de las principales fuerzas políticas: Juan D. Perón (PJ) y Ricardo Balbín (UCR)- y un conjunto de transformaciones socioculturales entre las que se encuentra el ascenso de la televisión como medio masivo de comunicación. Con un alcance del estudio descriptivo y de temporalidad longitudinal, el método seleccionado para analizar las 221 unidades (que incluyen tanto propaganda gráfica como spots televisivos) es el análisis de contenido, permitiendo así obtener datos nominales cuantificables. El resultado principal de la investigación denota un punto de inflexión en la forma de hacer campañas electorales en términos generales, con notables diferencias entre los partidos.

Ankle fractures are among the most common types of fractures seen in the United States. Few studies have analyzed the use of a locking compression plate (LCP) hook plate in the fixation of malleolar fractures. The goal of this study was to analyze postoperative outcomes in malleolar fractures fixed with a 3.5-mm LCP hook plate. A cohort of 74 patients with ankle fractures treated operatively with hook plates between 2011 and 2021 by a single orthopedic surgeon was retrospectively reviewed. Time to union, duration of non–weight bearing, final range of motion, postoperative complications, demographics, and comorbidities were recorded. A total of 66 patients fulfilled our inclusion criteria. There were 5 isolated medial malleolar, 34 bimalleolar, and 27 trimalleolar fractures. There were 46 women and 20 men with a mean age of 60.9±18.9 years. Fourteen patients had diabetes, 27 had osteoporosis, and 4 were current or former tobacco users. All patients achieved union, with a mean time to union of 10.9±5.3 weeks. The mean time to weight bearing was 50.2±18.4 days. The mean length of follow-up was 8.1±5.6 months. At final follow-up, mean dorsiflexion was 9.9°±4.3° and mean plantarflexion was 14.1°±5.1°. Six patients experienced postoperative complications such as surgical site infections and posttraumatic osteoarthritis. This study demonstrates that the use of a 3.5-mm LCP hook plate in the operative fixation of malleolar fractures has a high rate of union while maintaining low rates of postoperative complications. [ Orthopedics . 202x;4x(x):xx–xx.]

This study examined the epidemiology of self-harm emergency department (ED) visits among Asian American and Pacific Islander (AAPI) youth, and associated factors.We used California ED visit records in 2010 and 2011 to calculate incidence rates of self-harm ED visits for AAPI versus non-Hispanic White (NHW) patients aged 10-29 years. Demographic and clinical characteristics were compared for AAPI versus NHW patients presenting with self-harm. We used modified Poisson regression models to estimate the relative risk of recurrent ED self-harm visits for AAPI versus NHW patients and examined the association of insurance type and gender with recurrent self-harm among AAPIs.Rates of self-harm ED visits for young AAPI patients were 38 and 26 per 100,000 among females and males, respectively. Although AAPI patients presenting with self-harm were equally or less likely than NHW patients to have comorbid psychological and substance use diagnoses at their index visit, they were 25% more likely to be admitted to hospital. However, they were 40% less likely to have a recurrent ED self-harm visit. Among AAPI patients, those who used Medicaid were significantly more likely than those with other insurance to be admitted as inpatients.Young AAPI patients presenting to EDs with deliberate self-harm have different sociodemographic and clinical profiles compared to NHW patients. Our study also demonstrates significant heterogeneity in risk of recurrent self-harm by gender and insurance type among AAPI patients. This information may be useful for future intervention programs among self-harming AAPI youth.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106 ) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non–small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data. METHODS Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points. RESULTS At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis. CONCLUSION These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

The COVID-19 pandemic has influenced people's lives in diverse ways. The authors utilized latent class analysis (LCA), a person-centered approach, to examine distinct patterns of COVID-related stressors and their associations with alcohol-related, mental health, and quality of life outcomes. Participants were 463 adults who completed the baseline assessment of the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol Study from June 2020 to January 2022. Using cross-sectional data, three analytic methods (continuous sum score, categorical grouping, and LCA) were applied to model 17 COVID-related stressors. Regression analyses indicated higher COVID-related stress and endorsement of four or more COVID-related stressors were generally associated with worse health-related outcomes. LCA revealed four classes: Class 1: Minimal COVID-Related Impact (51.6%); Class 2: Work Interruptions (24.8%); Class 3: Family/Friends Affected by COVID (14.5%); and Class 4: Serious Financial Stress (9.1%). Racial/ethnic minorities were more likely to be in Class 3, whereas individuals with more years of education and higher income were less likely to be in Class 4. Individuals with a history of alcohol use disorder were more likely to be in Classes 2 and 4. Compared with Class 1, Class 4 reported highest levels of perceived stress, problematic alcohol use, anxiety symptoms, depressive symptoms, alcohol craving, loneliness, drinking to cope, and lowest levels of physical, psychological, social, and environment quality of life. COVID-related stressors disproportionately affected minority and vulnerable groups. Individuals who experienced multiple financial stressors had the greatest risk for negative health-related outcomes and may benefit from holistic interventions and community outreach. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24-48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract "affected" white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80-100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.

This cross-sectional study examines state Medicaid coverage of human papillomavirus vaccination in adults aged 27 to 45 years and discusses the implications of the results for dermatologists.

Special education advocacy programs support families to secure services for their children with intellectual and developmental disabilities. Although research demonstrates the efficacy of one such program (the Volunteer Advocacy Project), its effectiveness when replicated by others is unknown. Replication research is critical to ensure that programs can remain effective. The purpose of this study was to explore the adaptation process for two agencies that replicated an advocacy program. Quantitative and qualitative data were collected to examine feasibility, acceptability, and effectiveness. Although it took resources to replicate the advocacy program, agencies reported ongoing implementation would be easier once adaptations were completed. The adapted programs were effective in increasing participants' knowledge, empowerment, advocacy, and insiderness. Implications for research and practice are discussed.

Although social groups have “insiders,” this construct has not been measured within the disability advocacy community. Examining 405 individuals who applied for an advocacy training program, this study examined the nature of insiderness within the disability advocacy community and ties to individual roles. Participants showed differences in mean ratings across 10 insider items. A principal components analysis revealed two distinct factors: Organizational Involvement and Social Connectedness. Non-school providers scored highest on Organizational Involvement; family members/self-advocates highest on Social Connectedness. Themes from open-ended responses supported the factors and showed differences in motivation and information sources across insiderness levels and roles. Qualitative analysis revealed two additional aspects of insiderness not addressed in the scale. Implications are discussed for future practice and research.

SLE is a global health concern that unevenly affects certain ethnic/racial groups. Individuals of Asian, Black, Hispanic and Indigenous ethnicity/race are amongst those who experience increased prevalence, incidence, morbidity and mortality. Population-based surveillance studies from many regions are few and often still in nascent stages. Many of these areas are challenged by restricted access to diagnostics and therapeutics. Without accurately capturing the worldwide burden and distribution of SLE, appropriately dedicating resources to improve global SLE outcomes may be challenging. This review discusses recent SLE epidemiological studies, highlighting the challenges and emerging opportunities in low- and middle-income countries. We suggest means of closing these gaps to better address the global health need in SLE.

Within the field of suicidology, high-achieving Asian American adolescents are an under-researched at-risk population. The present paper reviews the existing literature on this topic, addressing the increase in suicidal ideation and suicide attempts within this at-risk group, and explores ecologically valid social work interventions. School social workers are first responders to these at-risk youth and must be well-versed in the risk-factors, including parental resistance to treatment, within the specific populations they serve. To illustrate the relevant issues, a case example is presented of an adolescent Bangladeshi male who attempted suicide while attending school. Finally, this paper recommends suicide prevention measures, including a culturally appropriate suicide assessment and family therapy.

Despite the ubiquity of campus food insecurity, it has often been an issue silent, faceless, and ignored. Only within the last decade has it received recognition as a national crisis (McCoy et al., 2022). Perhaps because college is widely regarded as a privileged endeavor, requiring substantial tuition dollars from students and their families, food insecurity has not received the attention or resources that it deserves. Although policy-level and administrative changes should take the lead in addressing the issue, student-led groups have played a role in initiating action. Campus Food Shed (CFS), a University of Wisconsin-Madison student organization, seeks to address these concerns. Spearheaded by students, the organization partners with local grocery stores and research farms to distribute leftover food items, assisting peers across the UW-Madison campus with access to free, nutritious food. As UW-Madison alumni, our experiences through CFS have brought to our attention nationwide concerns regarding food insecurity (Goldrick-Rab et al., 2017). In addition, studies across the country over the last five years have demonstrated the severity of food insecurity for many college and university students (Baker-Smith et al., 2020; Broton & Cady, 2020; Broton & Goldrick-Rab, 2017; Laska et al., 2020; Watson et al., 2017). . . .

Almost all patients with multiple myeloma (MM) eventually relapse, either asymptomatically or with end-organ damage. However, it remains unclear whether initiating therapy at the time of biochemical progression (BP) improves the outcomes compared with initiating therapy at the clinical progression (CP) stage. Here, we retrospectively assessed 1347 patients with relapsed MM. Most progressions were BP (60.4%); 39.6% had CP. The most prevalent symptoms at relapse were new or evolving bone disease (80.9%), anemia (38.0%), and renal failure (12.7%). Patients with BP had longer median time from second-line treatment to the next treatment compared with patients who had CP (17.0 vs 9.6 months; P < .001) as well as longer median overall survival from first relapse (59.4 vs 26.2 months; P < .001). Male sex (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.02-2.18; P = .04), plasma cell labeling index ≥2% (OR, 1.58; 95% CI, 1.02-2.45; P = .04), and extramedullary disease at diagnosis (OR, 1.84; 95% CI, 1.08-3.13; P = .03) were associated with higher risk of CP, whereas very good partial remission or better had decreased risk of CP (OR, 0.62; 95% CI, 0.43-0.91; P = .02). To conclude, patients with CP have inferior postprogression outcomes compared with patients who have BP. Patients with deeper response to first-line therapy are less likely to develop CP. The presence of a specific CRAB (C, hypercalcemia; R, renal failure; A, anemia; B, bone disease) symptom at diagnosis predicts for the development of similar CRAB symptoms at relapse.

Continued star formation over the lifetime of a galaxy suggests that low metalicity gas is steadily flowing in from the circumgalactic medium. Also, cosmological simulations of large-scale structure formation imply that gas is accreted onto galaxies from the halo inside which they formed. Direct observations are difficult, but in recent years observational indications of gas inflows from a circumgalactic medium were obtained. Here we suggest an indirect observational probe: looking for large-scale (exceeding few kpc) turbulence caused by the accretion. As a specific example we consider an accretion flow coplanar with the galaxy disk, and argue that Kelvin-Helmholtz turbulence will be generated. We employ a semi-analytic model of turbulence and derive the expected turbulence power spectrum. The latter turns out to be of a distinctive shape that can be compared with observational power spectra. As an illustrative example we use parameters of the Milky Way galaxy., Comment: 5 pages, 4 figures. Submitted to MNRAS. Comments are welcome

Motivated by some models of pattern formation involving an unoriented director field in the plane, we study a family of unoriented counterparts to the Aviles–Giga functional. We introduce a nonlinear $\operatorname {\mathrm {curl}}$ operator for such unoriented vector fields as well as a family of even entropies which we call ‘trigonometric entropies’. Using these tools, we show two main theorems which parallel some results in the literature on the classical Aviles–Giga energy. The first is a compactness result for sequences of configurations with uniformly bounded energies. The second is a complete characterization of zero-states, that is, the limit configurations when the energies go to 0. These are Lipschitz continuous away from a locally finite set of points, near which they form either a vortex pattern or a disclination with degree 1/2. The proof is based on a combination of regularity theory together with techniques coming from the study of the Ginzburg–Landau energy. Our methods provide alternative proofs in the classical Aviles–Giga context.

Background The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM). Methods Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD. Results CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r ⩾ 0.45, p = 0.002). Conclusions This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.