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Introduction The need to train oncologists to address the complexities of the aging population has been a focus of educational initiatives and strategies since the 1980s. However, large gaps in the dissemination and implementation of geriatric oncology curricula are still present. Currently, few resources exist for oncology training programs to implement a formal geriatric oncology curriculum. We aimed to create a formalized introductory course to teach oncology and geriatrics trainees the principles of geriatric oncology. Methods Curriculum presentations were delivered to both hematology/oncology and geriatrics fellows during five 1-hour didactic/workshop sessions over a 2-month period. In addition to didactic presentations, sessions included interactive learning components and a case-based workshop. Evaluation of the curriculum was conducted through pre- and postcourse knowledge and competency assessments, as well as individual session satisfaction surveys. Results Fifteen (11 hematology/oncology and four geriatric medicine) clinical fellows participated in the first presentation of this curriculum during the 2022–2023 academic year. The mean score on the precourse knowledge assessment was 7.1 (SD = 2.5) out of a maximum score of 15 compared with a mean score on the postcourse knowledge assessment of 9.8 (SD = 3.0; CI: 8.0–11.6; t = −2.5; p = .02). Discussion Course content was successfully implemented into the hematology/oncology and geriatric medicine fellowship core curriculum using the above methods. Future directions include presentation of course material to incoming trainees, content refinement based on satisfaction surveys, and interdisciplinary adaptation for trainees in other health care disciplines (e.g., nursing, advanced practice providers, etc.).

Introduction There are no established methods to identify children with atypical diabetes for further study. We aimed to develop strategies to systematically ascertain cases of atypical pediatric diabetes using electronic medical records (EMR).Research design and methods We tested two strategies in a large pediatric hospital in the USA. Strategy 1: we designed a questionnaire to rule out typical diabetes and applied it to the EMR of 100 youth with diabetes. Strategy 2: we built three electronic queries to generate reports of three atypical pediatric diabetes phenotypes: unknown type, type 2 diabetes (T2D) diagnosed

Background: Physical therapy (PT) has an important role in Integrative Oncology programs, addressing the unique physical health needs of individuals with cancer through exercise counseling. We share our experience with the PT component of our telehealth comprehensive lifestyle modification program including data from our first cohort of patients. Methods: The PT component of our lifestyle modification program included 6 one-hour synchronous video sessions (30 minutes exercise education, 30 minutes exercise) over the 12-week program. Participants received handouts electronically that included information regarding each week’s exercise-related topic, as well as weekly exercise assignments. Outcomes included weight, days of aerobic exercise, minutes of aerobic exercise, and days of strengthening exercise. Six patients completed the program and submitted an anonymous exit survey providing qualitative feedback on the program. Results: On average, patients reported engaging in aerobic exercise 4 days per week and strength training 2 days per week after the intervention. There were notable increases in days of strength training. Patients lost an average of 4.2% of their body weight over the course of the 12-week program. Qualitative feedback showed that the first cohort of patients described the telehealth program as enjoyable, valuable, and convenient. Discussion: Physical therapy exercise programs can be modified and tailored for delivery in a telehealth environment. Increased patient access remains a strength of this model, serving to equip patients with the tools needed for increasing aerobic and strength training activity. Overall, the program was implemented successfully, and the anonymous feedback survey completed after program completion showed high patient satisfaction.

Objective To summarize patient characteristics and outcomes for the historical and current methods of long-segment tracheal replacement in humans.

IMPORTANCE:. Electrographic seizures (ESz) are seizures without prominent motor activity diagnosed with electroencephalogram and are a common complication in critically ill patients with alterations of consciousness. Previous studies suggested clinical signs, including ocular movement abnormalities, facial/periorbital twitching, or remote seizure risk factors, are sensitive for presence of ESz. OBJECTIVES:. To assess the utility of clinical features in identifying ESz in critically ill patients with alterations of consciousness. DESIGN, SETTING, AND PARTICIPANTS:. This is a retrospective case-control study of 50 patients admitted to the University of North Carolina (UNC) Medical Center and UNC Rex Hospital. Inpatients older than 18 years old undergoing continuous video electroencephalogram (cEEG) were included. Patients admitted for neurologic diagnoses were excluded. A total of 25 patients with ESz (Sz-EEG) were matched with 25 controls by electroencephalogram duration ± 12 hours (No-Sz-EEG). Elements of patient’s history and physical findings previously shown to be sensitive for presence of ESz were collected. Descriptive statistical analyses were used. RESULTS:. Most patients were admitted to medical ICUs (72%; n = 36). There was no difference between groups in clinical findings previously shown to be sensitive for ESz. Positive and negative likelihood ratios for these findings generally fell between 1–2 and 0.5–1, respectively, indicating they are inaccurate predictors for ESz. Patients with ESz had significantly higher mortality (p = 0.012). CONCLUSIONS AND RELEVANCE:. Our matched case-control study showed that in the critically ill patient population hospitalized in tertiary care centers and admitted for non-neurologic primary diagnoses, incidence of ocular movement abnormalities, facial/periorbital twitching, and presence of remote risk factors for seizures had low predictive accuracy for ESz. However, these findings are not generalizable to patients with neurologic diseases or to other practice settings with different levels of access to cEEG. We concluded that in this exploratory analysis of hospitalized critically ill patients with non-neurologic diagnoses, these clinical signs did not reliably stratify risk for ESz on cEEG. However, further prospective studies are needed to better evaluate these conclusions.

Abstract Cissus quadrangularis is a succulent vine that degrades forests where it is not native by growing over trees and causing them to break or by impeding regeneration. Methods for its control have been tried but no satisfactory approach has been found yet. We carried out an experiment to analyze how much desiccation Cissus can endure before losing its ability to grow when rehydrated, using fragments of 0.5, 1, 2, and 3 internodes to test if desiccation tolerance was affected by fragment length. We found that Cissus remains viable after losing up to 80% of its weight, with shorter fragments losing viability (capacity to grow) at 70% weight loss. No fragments sustained viability at 90% water loss, establishing a critical threshold for Cissus desiccation tolerance. Our study also showed that shorter fragments (0.5 internodes) were less viable compared to longer ones (1, 2 or 3 internodes). Cissus has a remarkable tolerance to desiccation. Therefore, management strategies should ensure complete dehydration of Cissus fragments to prevent its regrowth. Reducing fragments to smaller sizes could amplify the effectiveness of control measures by reducing their viability, but risks of increasing propagule numbers should be considered.

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In this study, we develop new reverse engineering (RE) techniques to identify the organization of the synaptic inputs generating firing patterns of populations of neurons. We tested these techniques in silico to allow rigorous evaluation of their effectiveness, using remarkably extensive parameter searches enabled by massively-parallel computation on supercomputers. We chose spinal motoneurons as our target neural system, since motoneurons process all motor commands and have well-established input-output properties. One set of simulated motoneurons was driven by 300,000+ simulated combinations of excitatory, inhibitory, and neuromodulatory inputs. Our goal was to determine if these firing patterns had sufficient information to allow RE identification of the input combinations. Like other neural systems, the motoneuron input-output system is likely non-unique. This non-uniqueness could potentially limit this RE approach, as many input combinations can produce similar outputs. However, our simulations revealed that firing patterns contained sufficient information to sharply restrict the solution space. Thus, our RE approach successfully generated estimates of the actual simulated patterns of excitation, inhibition, and neuromodulation, with variances accounted for ranging from 75–90%. It was striking that nonlinearities induced in firing patterns by the neuromodulation inputs did not impede RE, but instead generated distinctive features in firing patterns that aided RE. These simulations demonstrate the potential of this form of RE analysis. It is likely that the ever-increasing capacity of supercomputers will allow increasingly accurate RE of neuron inputs from their firing patterns from many neural systems.

Background: Women entering surgical residencies must determine which programs best fit their career and family goals. The purpose of this study was to determine if breastfeeding policies are available on otolaryngology residency program websites. Methods: A total of 122 publicly available otolaryngology residency program websites were reviewed for the presence of a breastfeeding policy and lactation information. The percentage of residents and faculty that are women in each program as well as the program’s region, size, and affiliation with a top 50 hospital for ear, nose, and throat care were determined. Frequencies and nonparametric analyses were calculated when appropriate. Results: None of the otolaryngology residency programs had a breastfeeding policy posted directly on their website. A link to a Graduate Medical Education (GME) website that contained a breastfeeding policy was present on 20 (16.4%) program websites, and 31 websites (25.4%) had information about lactation facilities on the GME website or another page that could be found through the search bar; 17 (23.0%) of the large residency programs contained the link to the GME website, whereas only 3 (6.25%) of the small programs did (p = 0.015). Residency programs that were affiliated with a top 50 hospital for ear, nose, and throat care were more likely to have a link to the GME website with a breastfeeding policy than those not affiliated (13 [29.5%] vs. 7 [8.9%], respectively; p = 0.003). Conclusion: Otolaryngology residency programs do not provide breastfeeding policies directly on their websites.

BackgroundCraniosacral osteopathic manipulative medicine—also known as craniosacral therapy (CST)—is a widely taught and used component of osteopathic medicine. This paper seeks to systematically review and conduct a meta-analysis of randomized controlled trials assessing the clinical effectiveness of CST compared to standard care, sham treatment, or no treatment in adults and children.MethodsA search of Embase, PubMed, and Scopus was conducted on 10/29/2023 and updated on 5/8/2024. There was no restriction placed on the date of publication. A Google Scholar search was conducted to capture grey literature. Backward citation searching was also implemented. All randomized controlled trials employing CST for any clinical outcome were included. Studies not available in English as well as studies that did not report adequate data were excluded. Multiple reviewers were used to assess for inclusions, disagreements were settled by consensus. PRISMA guidelines were followed in the reporting of this meta-analysis. Cochrane’s Risk of Bias 2 tool was used to assess for risk of bias. All data were extracted by multiple independent observers. Effect sizes were calculated using a Hedge’s G value (standardized mean difference) and aggregated using random effects models. The GRADE system was used to assess quality of evidence.ResultsThe primary study outcome was the effectiveness of CST for selected outcomes as applied to non-healthy adults or children and measured by standardized mean difference effect size. Twenty-four RCTs were included in the final meta-analysis with a total of 1,613 participants. When subgroup analyses were performed by primary outcome only, no significant effects were found. When secondary outcomes were included in subgroup analyses, results showed that only Neonate health, structure (g = 0.66, 95% CI [0.30; 1.02], Prediction Interval [−0.73; 2.05]) and Pain, chronic somatic (g = 0.34, 95% CI [0.18; 0.50], Prediction Interval [−0.41; 1.09]) show reliable, statistically significant effect. However, these should not be interpreted as positive results as wide prediction intervals, high bias, and statistical limitations temper the real-world implications of this finding.Conclusions and relevanceCST demonstrated no significant effects in this meta-analysis, indicating a lack of usefulness in patient care for any of the studied indications.Pre-registration available at https://doi.org/10.17605/OSF.IO/54K6G.Systematic Review Registrationhttps://osf.io/54k6g.

Although there is an established link between smaller hippocampal volume and anxiety, the longitudinal relations between hippocampus structure and anxiety in diverse youth are not well understood. The present longitudinal study investigated hippocampal volumes related to anxiety symptoms in a sample of Black 8–14-year-old youth (N = 64), a population historically underrepresented in neuroimaging research. Smaller hippocampal volumes were associated with greater anxiety symptoms independent of age, sex, intracranial volume and trauma exposure. Exploratory longitudinal analyses showed smaller hippocampal volume as a predictor for anxiety symptoms (n = 37) and not a consequence of anxiety symptoms (n = 32), however results were inconclusive as this finding was no longer significant after correcting for baseline anxiety symptoms. Overall, this data increases our understanding of potential neurobiological mechanisms for anxiety in a high-risk sample of Black youth and suggests future directions into studying trajectories of developmental risk.

Background Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.Methods DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity.Results Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3–4 events. There were no grade 5 events.Conclusion Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary.Trial registration number NCT02834013.

ABSTRACT Haemophilus parainfluenzae (Hp) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how Hp interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain (Hp 392) and oral isolate EL1 (Hp EL1), we show that the essential genomes of Hp 392 and Hp EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.IMPORTANCEHaemophilus parainfluenzae is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth. H. parainfluenzae correlates with good oral health and may play a role in preservation of healthy host status. Also, H. parainfluenzae can cause opportunistic infections outside of the oral cavity. To date, little is known about how H. parainfluenzae colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.

Summary: The ability to visualize and track multiple biological processes in vivo in real time is highly desirable. Bioluminescence imaging (BLI) has emerged as an attractive modality for non-invasive cell tracking, with various luciferase reporters enabling parallel monitoring of several processes. However, simultaneous multiplexed imaging in vivo is challenging due to suboptimal reporter intensities and the need to image one luciferase at a time. We report a multiplexed BLI approach using a single substrate that leverages bioluminescence resonance energy transfer (BRET)-based reporters with distinct spectral profiles for triple-color BLI. These luciferase-fluorophore fusion reporters address light transmission challenges and use optimized coelenterazine substrates. Comparing BRET reporters across two substrate analogs identified a green-yellow-orange combination that allows simultaneous imaging of three distinct cell populations in vitro and in vivo. These tools provide a template for imaging other biological processes in vivo during a single BLI session using a single reporter substrate.

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 [...]

In this study, we explore the potential of data from large-scale assessments to provide insights into how students' environmental knowledge could address the global challenge of environmental threats to humanity and the transition to sustainable development. We analyze data from the 2015 PISA survey to understand the extent to which 15-year old students in 54 countries are aware of these challenges. We find that students' science activities, self-efficacy and environmental knowledge are positively associated with their awareness about environmental challenges. Students' environmental awareness, in turn, is associated with environmental pessimism, or their outlook on the future of environmental issues. Students who are more engaged with environmental science are more aware about environmental issues and feel less optimistic that environmental issues will improve in the future. Such pessimistic attitudes about the future may be a precursor to pro-environmental behavior. Our results provide a cross-national picture of students' engagement with environmental issues and insight into the potential of large-scale assessment data to inform environmental education policies promoted by individual countries and international organizations.

Climate change may impact human health through the influence of weather on environmental transmission of diarrhea. Previous studies have found that high temperatures and heavy precipitation are associated with increased diarrhea prevalence, but the underlying causal mechanisms have not been tested and validated. We linked measurements of Escherichia coli in source water (n = 1673), stored drinking water (n = 9692), and hand rinses from children

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Over the past two decades, research and clinical resources on clinical high risk (CHR) for psychosis have both expanded, with goals to better understanding risk and protective factors on the course of illness and inform early intervention efforts. However, some studies have highlighted potential sampling bias among CHR research studies, raising questions about generalizability of findings and inequitable access to early detection and intervention. The current study sought to explore these questions by comparing 94 participants in a CHR longitudinal monitoring study across North America (NAPLS-2) who converted to syndromal psychosis over the course of the study (CHR-CV) to 171 participants who presented for treatment at a localized first-episode psychosis service (FES) after converting. CHR-CV participants were significantly more likely to be White and have a college-educated parent, while FES participants were more likely to be Black and first- or second-generation immigrants. On average, CHR-CV participants were younger at onset of attenuated positive symptoms, had a longer period of attenuated symptoms prior to conversion, and were more likely to be treated with antipsychotics prior to conversion compared to those in FES programs. After controlling for time since conversion, CHR-CV participants had higher global functioning and were less likely to have experienced recent psychiatric hospitalization. Findings suggest that CHR research and FES clinics may be sampling from different populations, although conclusions are limited by inconsistent sampling frames and methods. Integrated early detection that targets defined geographic catchments may deliver more epidemiologically representative samples to both CHR research and FES.

Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem-cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, serotonin-producing pre-β cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β cell maturation and identify sex hormones as drivers of β cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem-cell-derived islets and a framework for manipulating cell identities and maturity.

The Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report provides a summary of the proceedings from the workshop. The goals of the workshop were to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into six major theme areas, including 1) pancreas anatomy and physiology, 2) diabetes in the setting of exocrine disease, 3) metabolic influences on the exocrine pancreas, 4) genetic drivers of pancreatic diseases, 5) tools for integrated pancreatic analysis, and 6) implications of exocrine-endocrine cross talk. For each theme, multiple presentations were followed by panel discussions on specific topics relevant to each area of research; these are summarized here. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

BackgroundWhether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.MethodsIn a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated.ResultsAt a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group.ConclusionsAmong patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.

Background and objectivesProspective, deeply phenotyped research cohorts monitoring individuals with chronic neurologic conditions, such as multiple sclerosis (MS), depend on continued participant engagement. The COVID-19 pandemic restricted in-clinic research activities, threatening this longitudinal engagement, but also forced adoption of televideo-enabled care. This offered a natural experiment in which to analyze key dimensions of remote research: (1) comparison of remote vs in-clinic visit costs from multiple perspectives and (2) comparison of the remote with in-clinic measures in cross-sectional and longitudinal disability evaluations.MethodsBetween March 2020 and December 2021, 207 MS cohort participants underwent hybrid in-clinic and virtual research visits; 96 contributed 100 "matched visits," that is, in-clinic (Neurostatus-Expanded Disability Status Scale [NS-EDSS]) and remote (televideo-enabled EDSS [tele-EDSS]; electronic patient-reported EDSS [ePR-EDSS]) evaluations. Clinical, demographic, and socioeconomic characteristics of participants were collected.ResultsThe costs of remote visits were lower than in-clinic visits for research investigators (facilities, personnel, parking, participant compensation) but also for participants (travel, caregiver time) and carbon footprint (p < 0.05 for each). Median cohort EDSS was similar between the 3 modalities (NS-EDSS: 2, tele-EDSS: 1.5, ePR-EDSS: 2, range 0.6.5); the remote evaluations were each noninferior to the NS-EDSS within ±0.5 EDSS point (TOST for noninferiority, p < 0.01 for each). Furthermore, year to year, the % of participants with worsening/stable/improved EDSS scores was similar, whether each annual evaluation used NS-EDSS or whether it switched from NS-EDSS to tele-EDSS.DiscussionAltogether, the current findings suggest that remote evaluations can reduce the costs of research participation for patients, while providing a reasonable evaluation of disability trajectory longitudinally. This could inform the design of remote research that is more inclusive of diverse participants.

Nocardia is a genus of aerobic, filamentous, beaded, gram-positive bacteria ubiquitous in the environment, especially in soil, decomposing organic matter, and water. Nocardia spp. are opportunistic pathogens in immunocompromised hosts [...]