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Background and purpose: To analyze the relationship between cognitive processing speed, patient‐reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. Methods: Cross‐sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology‐enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi‐automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. Results: In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self‐reported physical disability, cognitive function, fatigue and social domains (adjusted R2 = 0.44, P < 0.001) as the strongest clinical predictors of PST score, whereas that of MRI variables included T2 lesion volume, whole‐brain fraction and cord atrophy (adjusted R2 = 0.42, P < 0.001). An inclusive model identified T2 lesion volume, whole‐brain fraction, self‐reported upper extremity function, cognition and social participation as the strongest predictors of PST score (adjusted R2 = 0.51, P < 0.001). There was significant effect modification by depression on the relationship between self‐reported cognition and PST performance. Employment status was associated with PST scores independent of age and physical disability. Conclusion: The PST score correlates with PROMs, MRI measures of focal and diffuse brain injury, and employment. The PST score is a feasible and meaningful measure for routine multiple sclerosis care. [ABSTRACT FROM AUTHOR]

Background and purpose: The purpose was to determine the test–retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self‐administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression‐based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. Methods: Substudy 1 assessed test–retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. Results: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician‐administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. Conclusions: The self‐administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting. [ABSTRACT FROM AUTHOR]

The Missouri Air Conservation Commission regulations include regulations that limit the amount of acceptable odor from confined animal feeding operations (CAFOs). The regulations concerning odor designate the use of a scentometer as a screening tool. The rules dictate that if an odor is detectable by an investigator at a dilution ratio of 5.4 using a scentometer then an air sample should be collected and sent to an olfactometry laboratory for an odor panel to determine the detection threshold and the intensity of the odor sample. The detection thresholds are determined following ASTM E679-91 and EN13725. The intensity is determined following ASTM E544-99. If the olfactometry laboratory determined the detection threshold of the sample to be above seven, then the CAFO would be in violation. If the olfactometry laboratory determined the intensity level to be above a level equivalent to 225 ppm of n-butanol, then the source of odor would be in violation. The CAFO odor rules came under scrutiny by representatives of the largest hog producer in the State of Missouri. Specifically, they argued that the detection threshold limit of seven in the CAFO portion of the rule was too low for the rule to realistically identify a violation. This paper presents the results of a study to find the appropriate regulatory level of odor as determined by laboratory olfactometry. The study took place from November 2001 to October 2002. Samples were collected from field locations that exhibited odor produced by confined animal feeding operations and from areas exhibiting no apparent odor. The odors were categorized based upon the scentometer level at which the odors were detectable, and then samples were sent to an odor evaluation laboratory for analysis by olfactometry. [ABSTRACT FROM AUTHOR]

A standard method for measuring and quantifying odour in the ambient air utilizes a portable odour detecting and measuring device known as a field olfactometer (US Public Health Service Project Grant A-58-541). The field olfactometer dynamically dilutes the ambient air with carbon-filtered air in distinct ratios known as "Dilutions-to-Threshold" dilution factors (D/Ts), i.e. 2, 4, 7, 15, etc. Thirteen US states and several cities in North America currently utilize field olfactometry as a key component of determining compliance to odour regulations and ordinances. A controlled environmental chamber was utilized, with hydrogen sulfide as the known test odorant. A hydrogen sulfide environment was created in this controlled chamber using an Advanced Calibration Designs, Inc. Cal2000 Hydrogen Sulfide Generator. The hydrogen sulfide concentration inside the chamber was monitored using an Arizona Instruments, Inc. Jerome Model 631 H2S Analyzer. When the environmental chamber reached a desired test concentration, test operators entered the chamber. The dilution-to-threshold odour concentration was measured using a Nasal Ranger Field Olfactometer (St Croix Sensory, Inc.) and a Barnebey Sutcliffe Corp. Scentometer. The actual hydrogen sulfide concentration was also measured at the location in the room where the operators were standing while using the two types of field olfactometers. This paper presents a correlation between dilution-to-threshold values (D/T) and hydrogen sulfide ambient concentration. For example, a D/T of 7 corresponds to ambient H2S concentrations of 5.7-15.6 µg/m³ (4-11 ppbv). During this study, no significant difference was found between results obtained using the Scentometer or the Nasal Ranger® (r = 0.82). Also, no significant difference was found between results of multiple Nasal Ranger® users (p = 0.309). The field olfactometers yielded hydrogen sulfide thresholds of 0.7-3.0 µg/m³ (0.5-2.0 ppbv). Laboratory olfactometry yielded comparable thresholds of 0.64-1.3 µg/m³ (0.45-0.9 ppbv). These thresholds are consistent with published values. [ABSTRACT FROM AUTHOR]

Observations of crack damage in the tooth structure from in vivo studies and in vitro experimental thermal cycling studies were combined with numerical analysis techniques to identify and isolate the influence of thermal stresses on the creation and propagation of cracks in teeth. The factors considered in this study included: (a) variations in tooth type or geometry (molar, bicuspid, etc.), (b) tooth age, (c) material properties of the tooth, (d) the magnitude of the change in the temperature of the environment surrounding the tooth, and (e) the thermal resistance between the tooth and the medium surrounding the tooth. [ABSTRACT FROM AUTHOR]

The service-learning pedagogy attempts to enhance student learning by integrating academic study with meaningful community service. This paper discusses lessons learned when attempting to integrate direct service (having S-L students provide science lessons for primary students) and indirect service (having S-L students prepare curriculum guides for use by primary teachers) to maximize academic learning in a course entitled “Ecology: The Science of the Environment” at Lingnan University in Hong Kong. Although the course covered fewer topics when taught using the service-learning pedagogy, S-L students reported that participating in the service-learning project (i) increased their academic learning, (ii) enhanced their interest in science, and (iii) improved their communication and problem solving skills. Based on student feedback received, attempts were made to improve the service-learning experience by (i) altering the course outline so that S-L students have learned the material in class before sharing with the primary students, (ii) providing more input to the focus of their topics, (iii) allowing S-L students to interact with the primary students during their on-site orientation, and (iv) encouraging the primary school teachers to provide immediate feedback to the S-L students at the end of each lesson.

Background: Midwife-managed programmes of care are being widely implemented although there has been little investigation of their efficacy. We have compared midwife-managed care with shared care (ie, care divided among midwives, hospital doctors, and general practitioners) in terms of clinical efficacy and women's satisfaction.Methods: We carried out a randomised controlled trial of 1299 pregnant women who had no adverse characteristics at booking (consent rate 81.9%). 648 women were assigned midwife-managed care and 651 shared care. The research hypothesis was that compared with shared care, midwife-managed care would produce fewer interventions, similar (or more favourable) outcomes, similar complications, and greater satisfaction with care. Data were collected by retrospective review of case records and self-report questionnaires. Analysis was by intention to treat.Findings: Interventions were similar in the two groups or lower with midwife-managed care. For example, women in the midwife-managed group were less likely than women in shared care to have induction of labour (146 [23.9%] vs 199 [33.3%]; 95% CI for difference 4.4-14.5). Women in the midwife-managed group were more likely to have an intact perineum and less likely to have had an episiotomy (p = 0.02), with no significant difference in perineal tears. Complication rates were similar. Overall, 32.8% of women were permanently transferred from midwife-managed care (28.7% for clinical reasons, 3.7% for non-clinical reasons). Women in both groups reported satisfaction with their care but the midwife-managed group were significantly more satisfied with their antenatal (difference in mean scores 0.48 [95% CI 0.41-0.55]), intrapartum (0.28 [0.18-0.37]), hospital-based postnatal care (0.57 [0.45-0.70]), and home-based postnatal care (0.33 [0.25-0.42]).Interpretation: We conclude that midwife-managed care for healthy women, integrated within existing services, is clinically effective and enhances women's satisfaction with maternity care. [ABSTRACT FROM AUTHOR]

Rural regions face significant health care disparities, including decreased access to insurance, increased access barriers to specialty care, worse medical outcomes, and increased mortality rates. People with multiple sclerosis (MS) residing in rural regions in the United States, as well as globally, face similar barriers to accessing MS care and experience poorer disease outcomes. Barriers to health care access include cultural and financial constraints, scarcity of services, a lack of trained physicians, insufficient public transport, and poor availability of broadband internet service. The Appalachian region, which contains a high degree of rurality, experiences increased disparities compared with the rest of the nation and can be used to highlight the unique challenges rural populations face. Appalachian residents can identify as private, and mistrust is a major factor in providing health care. Increasing the quantity and retention of Appalachian providers is essential to building trust. Still, it has proved difficult due to issues with compensation, taxes, malpractice fees, adverse actions against physicians, and high turnover rates. Telehealth interventions such as Project ECHO (Extension for Community Healthcare Outcomes) have improved rural outcomes in multiple diseases, including MS, but limited technology and technological literacy in rural areas impede the implementation of these interventions. Given the increasing rural population and ongoing disparities these communities face, there is a need to develop targeted interventions to improve access and outcomes in rural populations., (© 2025 Consortium of Multiple Sclerosis Centers.)

Background: A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS)., Objectives: The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups., Methods: The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial., Results: For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening ( p < 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial., Conclusion: Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.M. serving on scientific advisory boards for Genzyme and Genentech and research support from AHRQ, Biogen, NIH, and Novartis. R.B. received consultant fees for Biogen, Genentech, Genzyme, and Novartis; research support from Biogen, Genentech, and Novartis; and shares rights to intellectual property underlying the Multiple Sclerosis Performance Test, currently licensed to Qr8 Health and Biogen. D.O. received research support from Genentech, Genzyme, and Novartis and consulting fees from Biogen, Genentech-Roche, Genzyme, Novartis, and Merck. R.T.N. has consulted for Alexion Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, EMD Serono, Horizon Therapeutics, Lundbeck, and TG Therapeutics. X.J. and Z.S. are the employees of and may hold stock/stock options in Biogen. N.L. is the former employee of and may hold stock/stock options in Biogen. R.H. and J.v.B are the former employees of and may hold stock/stock options in Biogen and TW1 Healthcare and consultant for International Registry for Alzheimer’s Disease and other dementias (InRAD). N.C. is the former employee of and may hold stock/stock options in Biogen and current employee of Janssen Scientific Affairs, LLC. CB. is the former employee of and may hold stock/stock options in Biogen and current employee of Novartis. J.J. and J.A. have no disclosures.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms. Time to relapse and MRI activity were compared using Kaplan-Meier curves and Cox regression models. There was no significant difference for either time to relapse (p = 0.34) or MRI activity (p = 0.15) in PwMS+ICIs compared to controls., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Using the Five Cs model of positive youth development (PYD), this study aimed to provide a socio-structural and cultural understanding of PYD in Indigenous Tayal youth by examining the specificity in the development of Five Cs (Competence, Confidence, Character, Caring, and Connection) between Tayal and Han youth in Taiwan., Methods: A sample of 847 Tayal and Han adolescents (43.8% Tayal, 47.9% girls, M age  = 14.83, SD = 0.50) were drawn from a larger study (September 2014 to August 2017). Adolescent participants completed questionnaires asking about their Five Cs, contribution behavior, and depressive symptomatology., Results: Measurement invariance was conducted to explore specificity between Tayal and Han youth's Five Cs performance. A bi-factor Five Cs model was identified and partial metric and partial scalar measurement invariance was established between the two samples. Across both groups an overarching PYD factor, which was associated with increased contribution and lower depressive symptomatology, was identified. Specificity was observed in the Tayal sample, particularly relating to indicators of Competence, Character, Caring, and Connection., Conclusion: The findings of this study provide a sociocultural-informed lens regarding the specificity of development in Tayal youth. Character, Caring, and Connection appear to contribute significantly more to the overall PYD for Tayal adolescents than their Han peers. Findings relating to Competence suggest that the educational environment may not be aligned with the learning style of Tayal youth. This study has policy and practical implications for Tayal youth, and can further help inform program development in Taiwan and internationally., (© 2024 Foundation for Professionals in Services to Adolescents.)

Background: Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience., Methods: This two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes., Conclusion: The results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions., Trial Registration: NCT05660187., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marisa McGinley has received research support from the National Institutes of Health, Novartis, Biogen, and Genentech. She has also received consulting fees from Genentech, EMD Serono, and Octave. Josh Carlson has received research support from the National Institutes of Health and the Institute for Clinical and Economic Review. He has also received consulting fees from Genentech, Pfizer, and Takeda. Jennifer Reihm reports no disclosures. Matthew Plow has received research support from the NIH, American Heart Association, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, Consortium of Multiple Sclerosis Centers, Department of Defence, Seibyl Foundation. Megan Roser reports no disclosures. Nikki Sisodia reports no disclosures. Jeffrey A. Cohen has received personal compensation for consulting for Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiNS Therapeutics, INMune, and Sandoz; and serving as an Editor of Multiple Sclerosis Journal. Anita D. Misra-Hebert has received research support from the Patient-Centered Outcomes Research Institute, National Institutes of Health, Agency for Healthcare Research and Quality, Ohio Department of Medicaid, Bayer, Novo Nordisk and Merck. Ann Lazar has received research support from the PCORI, NIH, DOD, and the University of California Office of the President Historically Black Colleges and University Initiative. She serves on NIH funded Data and Safety Monitoring Board (DMSB). She also receives funding for her role as the Statistical Editor for World Journal of Surgery and International Journal of Radiation Oncology, Biology, Physics. Riley Bove has received research support from NIH, DOD, National Multiple Sclerosis Harry Weaver Award, and from Biogen, Novartis, Eli Lilly and F Hoffman-LaRoche. She has received personal advisory board or consulting fees from EMD Serono, Horizon, Janssen, and TG Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS., Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS., Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes., Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod., Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes., (© The Author(s), 2024.)

Foraging theory has been a remarkably successful approach to understanding the behavior of animals in many contexts. In patch-based foraging contexts, the marginal value theorem (MVT) shows that the optimal strategy is to leave a patch when the marginal rate of return declines to the average for the environment. However, the MVT is only valid in deterministic environments whose statistics are known to the forager; naturalistic environments seldom meet these strict requirements. As a result, the strategies used by foragers in naturalistic environments must be empirically investigated. We developed a novel behavioral task and a corresponding computational framework for studying patch-leaving decisions in head-fixed and freely moving mice. We varied between-patch travel time, as well as within-patch reward depletion rate, both deterministically and stochastically. We found that mice adopt patch residence times in a manner consistent with the MVT and not explainable by simple ethologically motivated heuristic strategies. Critically, behavior was best accounted for by a modified form of the MVT wherein environment representations were updated based on local variations in reward timing, captured by a Bayesian estimator and dynamic prior. Thus, we show that mice can strategically attend to, learn from, and exploit task structure on multiple timescales simultaneously, thereby efficiently foraging in volatile environments. The results provide a foundation for applying the systems neuroscience toolkit in freely moving and head-fixed mice to understand the neural basis of foraging under uncertainty., Competing Interests: Declaration of Interests The authors declare no competing interests.

We show that the presence of anyons in the excitation spectrum of a two-dimensional system can be inferred from nonlinear spectroscopic quantities. In particular, we consider pump-probe spectroscopy, where a sample is irradiated by two light pulses with an adjustable time delay between them. The relevant response coefficient exhibits a universal form that originates from the statistical phase acquired when anyons created by the first pulse braid around those created by the second. This behavior is shown to be qualitatively unchanged by nonuniversal physics including nonstatistical interactions and small nonzero temperatures. In magnetic systems, the signal of interest can be measured using currently available terahertz-domain probes, highlighting the potential usefulness of nonlinear spectroscopic techniques in the search for quantum spin liquids.

We introduce a method that allows one to infer many properties of a quantum state-including nonlinear functions such as Rényi entropies-using only global control over the constituent degrees of freedom. In this protocol, the state of interest is first entangled with a set of ancillas under a fixed global unitary, before projective measurements are made. We show that when the unitary is sufficiently entangling, a universal relationship between the statistics of the measurement outcomes and properties of the state emerges, which can be connected to the recently discovered phenomeonon of emergent quantum state designs in chaotic systems. Thanks to this relationship, arbitrary observables can be reconstructed using the same number of experimental repetitions that would be required in classical shadow tomography [Huang et al., Nat. Phys. 16, 1050 (2020)NPAHAX1745-247310.1038/s41567-020-0932-7]. Unlike previous approaches to shadow tomography, our protocol can be implemented using only global Hamiltonian evolution, as opposed to qubit-selective logic gates, which makes it particularly well suited to analog quantum simulators, including ultracold atoms in optical lattices and arrays of Rydberg atoms.

Background and Purpose: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort., Methods: Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models., Results: Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare., Conclusions: Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Research on the impacts of exposure to workplace harassment (WH) is largely cross-sectional, and existing prospective studies generally are between two and five years of follow-up, with the longest US study being 10 years. However, the effects of exposure to WH may persist longer, particularly if exposure has been chronic. This study fills this gap by examining effects of prior exposure to chronic sexual and generalized WH on psychological distress and alcohol misuse over an approximately 25 year study period., Methods: Individuals originally recruited from a university-employed sample in the United States were surveyed at 8 time points from 1996-2007 and again in 2020-2021. A series of hybrid path analyses were tested on a sample of 2352 individuals, regressing recent outcomes on latent classes of harassment derived from earlier survey waves, controlling baseline outcomes and demographics. Model fit was assessed using a variety of fit statistics, and standardized regression coefficients were used to assess significance of individual pathways., Results: Prior exposure to chronic sexual harassment had significant direct associations with psychological distress, alcohol misuse, and recent stressors at follow-up. Prior exposure to chronic generalized harassment had significant direct associations with lower income and alcohol misuse. Both forms of WH were significantly indirectly associated with psychological distress through recent stressors at follow-up., Conclusions: Exposure to chronic WH is associated with long-term effects on psychological distress and alcohol misuse in a sample representing a wide variety of job types and racial/ethnic identities. Enforcement of anti-sexual harassment law and policies and enactment of policies and laws to prevent generalized harassment/workplace bullying are imperative for the protection of worker health., (© 2023. The Author(s).)

Based on the Ecological Stress-Based Model of Immigrant Worker Safety and Health, we hypothesized that occupational stress and physical safety would be negatively linked to workers' depression, which in turn, would increase family conflict and decrease youth prosocial behaviors. A total of 242 Latino immigrant cattle feedyard workers from Nebraska and Kansas (90.9% male; M age = 37.7 years) answered questions assessing depression, occupational stress, whether they had ever been injured at work, familial conflict, and youth prosocial behaviors. All four indirect relations among occupational stress and injury and the outcomes (family conflict and youth prosocial behaviors) via depressive symptomatology were significant. Additionally, ever injured was negatively related to youth prosocial behaviors and occupational stress was positively related to youth prosocial behaviors. The findings support our model and suggest that increased stress and work-related injuries on cattle feedyards are linked to mental health problems, which in turn, is linked to more conflict experienced at home and less youth prosocial behaviors. Feedyard employers should focus on improving safety culture including providing robust training in the workplace. Practical implications to improve availability and access to mental and behavioral health resources to mitigate negative family outcomes are provided., Competing Interests: The authors declare no conflict of interest.

Background: The electronic medical record (EMR) has revolutionized health care workflow and delivery. It has evolved from a clinical adjunct to a multifaceted tool, with uses relevant to patient care and research., Methods: A MEDLINE literature review was conducted to identify data regarding the use of EMR for multiple sclerosis (MS) clinical care and research., Results: Of 282 relevant articles identified, 29 were included. A variety of EMR integrated platforms with features specific to MS have been designed, with options for documenting disease course, disability status, and treatment. Research efforts have focused on early diagnosis identification, relapse prediction, and surrogates for disability status., Conclusions: The available platforms and associated research support the utility of harnessing EMR for MS care. The adoption of a core set of discrete EMR elements should be considered to support future research efforts and the ability to harmonize data across institutions., Competing Interests: FINANCIAL DISCLOSURES: Dr Swetlik declares no conflicts of interest., (© 2022 Consortium of Multiple Sclerosis Centers.)

Primary care mental health services need to expand to assist the increased number of people reporting mild to moderate mental health difficulties. In Ireland, the primary care mental health service has been recently enhanced through the employment of Assistant Psychologists (AP) in primary care psychology. This paper provides an early and brief evaluation of the impact of the AP-enhanced model through a tripartite approach to evaluation which utilises measures of throughput, output and stakeholder satisfaction. We use data from two sources; Health service key performance indicators, and a routinely gathered minimal dataset of client measures. Results indicate that the numbers of clients seen in the period rose by 16%, that AP-delivered treatments are beneficial for clients with mild to moderate mental health difficulties, and more than 80% of clients reported being 'totally satisfied' with the care received. The data provide early evidence that the AP model is beneficial in meeting clients' needs across a range of presentations within the service admission criteria, and that the AP-enhanced model may offer a satisfactory solution to primary care needs. However, further data collection is required, and additional stakeholder input is necessary for a complete evaluation of the assistant psychologist model in primary care., (© 2021 John Wiley & Sons Ltd.)

We introduce a model of nonunitary quantum dynamics that exhibits infinitely long-lived discrete spatiotemporal order robust against any unitary or dissipative perturbation. Ergodicity is evaded by combining a sequence of projective measurements with a local feedback rule that is inspired by Toom's "north-east-center" classical cellular automaton. The measurements in question only partially collapse the wave function of the system, allowing some quantum coherence to persist. We demonstrate our claims using numerical simulations of a Clifford circuit in two spatial dimensions which allows access to large system sizes, and also present results for more generic dynamics on modest system sizes. We also devise explicit experimental protocols realizing this dynamics using one- and two-qubit gates that are available on present-day quantum computing platforms.

Background: Socioeconomic disadvantage may be an important contributor to clinical outcomes in MS but is not well understood. Our objective was to examine the associations between Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage, with clinical outcomes., Methods: We assessed the longitudinal association between MS Performance Test (MSPT) and quality of life in Neurological Disorders (Neuro-QoL) measures with ADI quartiles (Q1: lowest deprivation - Q4 highest deprivation) in relapsing remitting MS (RRMS) and progressive MS cohorts., Results: Our study included 2,921 patients (65.8% RRMS and 34.1% progressive MS) with 13,715 visits. Patients living in the most disadvantaged areas had almost universal worsening on baseline MSPT and Neuro-QoL scores (p < 0.05) when compared to patients living in areas of lowest deprivation. Manual Dexterity Test (MDT) illustrated particular disparity as RRMS patients living in the greatest area of deprivation had MDT score which averaged 2.9 seconds longer than someone living in areas of least deprivation. Longitudinal analysis illustrated less favorable MSPT and Neuro-QoL outcomes across visits between Q1 versus Q4 ADI quartiles within in the RRMS cohort but not within the progressive MS cohort. After adjustment, linearly increasing area deprivation scores reflected less favorable Processing Speed Test (PST) and six Neuro-QoL outcomes among the RRMS cohort. Within the progressive cohort, higher deprivation was associated less favorable MDT, PST and 11 of 12 Neuro-QoL outcome measures., Conclusions: This study provides evidence for socioeconomic disadvantage as a risk factor for disability accrual in MS and may be targeted to improve care while informing resource allocation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The current study sought to determine how prosocial behaviors reflecting various motivations (altruistic and public prosocial behaviors) and situations (i.e., anonymous, compliant, dire, and emotional prosocial behaviors) jointly inform subtypes of prosocial personality groups. Undergraduates ( N  = 324, M age = 19.47 years, 80% female) completed a measure of these six prosocial behaviors (Prosocial Tendencies Measure-Revised). Latent profile analysis results supported a three-group solution: altruistic helpers (AH), public helpers (PH), and altruistic idealists (AI). The AH and AI profiles were defined by elevated altruistic prosocial behaviors, but the AH profile was higher on situational helping and socioemotive and sociocognitive correlates. The PH profile was characterized by elevated public prosocial behaviors and moderate levels of situational helping. These identified profiles support multiple competing ideas of the true nature of prosocial personality, but also introduce the possibility that some individuals idealize motives but fail to engage in behavior.

Informed by structural stigma theory, this article presents the results of two studies that explored mental health experiences of transgender, nonbinary, and gender-diverse (TNG) individuals and cisgender lesbian, gay, bisexual, and queer (LGBQ) individuals ( N = 523) prior to and following a state referendum to remove gender-based protections. In the Preelection Study, a path model explored relationships among individual factors (i.e., TNG identity, history of gender-based victimization), interpersonal variables (i.e., Referendum familiarity, exposure to Referendum-related messages, sexual orientation, and gender identity-specific social support), and mental health factors (i.e., Referendum-related anxiety and depressive symptomatology). Referendum-related anxiety mediated the relationships between TNG identity, gender-based victimization, sexual orientation and gender identity social support, and depressive symptomatology, explaining 40% of the variance in depressive symptomatology. Postelection, a subsample of participants ( N = 117) was used to test a model of differences from pre- to postelection. Neither TNG identity nor victimization predicted Postelection mental health, however, Referendum-related anxiety and depressive symptomatology were significantly lower following the ballot vote that retained gender-based rights. Clinical implications suggest sexual and gender minorities may report increased anxiety in the face of anti-lesbian, gay, bisexual, transgender, and queer (LGBTQ) legislation, which may be associated with heightened symptoms of depression. TNG people and LGBTQ people with histories of gender-based victimization may be more at risk for mental health concerns related to anti-TNG legislation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The current study was designed to address gaps in the existing literature by examining the role of discrimination and familism values as predictors of multiple forms of prosocial behaviors across time in a sample of recent immigrant Latino/a adolescents. Participants were 302 recent immigrant Latino/a adolescents (53.3% male; average age 14.51 years, range = 13-17). Data were collected from adolescents in two US cities: Los Angeles ( n = 150) and Miami ( n = 152). Adolescents completed measures of their own discrimination experiences, familism values, and tendency to engage in six forms of prosocial behaviors. Results indicated generally positive links between familism values and prosocial behaviors. Discrimination also positively predicted public prosocial behaviors and negatively predicted altruistic prosocial behaviors. We discuss the development of cultural processes and perceptions of discrimination experiences, and how these factors predict helping behaviors among immigrant adolescents., Competing Interests: Declaration of Conflicting Interest The authors declare that there is no conflict of interest.

With a growing population of Latinx youth immigrating to the United States, it is important to understand how Latinx youth adapt to mainstream U.S. culture. Given that the majority of research examining social development among recent immigrant adolescents has focused on negative adjustment outcomes, research examining positive social behaviors is needed to avoid deficit approaches to their development, gain a holistic understanding of youth development, and improve interventions with this population.This study examined the associations among trajectories in cultural integration and multiple prosocial behaviors among recent immigrant U.S. Latinx adolescents in Miami, Florida and Los Angeles, California. Adolescents ( N  =   302; 53.3% males; M age = 14.51 years) completed measures of integration and prosocial behaviors across six time points. Latent growth curve models indicated that integration significantly increased, though this growth tapered off over time. The growth in prosocial behaviors depended on the specific form of helping assessed. While the growth in altruistic and compliant prosocial behaviors was stagnant, there was an increase in anonymous prosocial behaviors and a decrease in public and dire prosocial behaviors. Emotional behaviors did not linearly change, though slightly tapered off by the final time points. Parallel process latent growth curve model results indicated positive correlations between the slopes of cultural integration and most forms of prosocial behaviors. These findings highlight the positive role of cultural integration as an acculturative process for U.S. Latinx youth and the multidimensionality of prosocial behaviors.

Background: Teleneurology has been well described for acute stroke, but outpatient use has been limited. At home, virtual visits have the potential to improve access to neurological care. Introduction: This study reports on the use of a personal device videoconferencing platform for outpatient neurologic follow-up visits. Materials and Methods: This is a cross-sectional study that identified all virtual neurologic follow-up visits completed by patients ≥18 years at a single institution over 4 years. Virtual visits were conducted by personal smartphone or computer via videoconferencing with a provider. Patients were asked to rate their overall experience with the visit and provider (five-point scale). Travel distance from the institution was calculated using patient's home addresses. Results: Three thousand nine hundred thirteen patients completed 5,581 virtual visits during the study (mean age 49.4 ± 17.0 years, 58.7% female). Number of virtual visits increased from 30 in year 1 to 4,468 in year 4. Virtual visits were completed in all outpatient neurologic subspecialties. A total of 30.1% of patients were local (<50 miles), 25.9% were near regional (50-150 miles), 21.7% were far regional (151-270 miles), and 22.2% were remote (>270 miles). A distance of 1,327,128 miles of travel was prevented across the 5,581 visits. On average, patients rated their overall virtual visit experience 4.7/5 ± 0.89 and rated their provider 4.9/5 ± 0.48. Discussion: Virtual visits prevented a substantial amount of travel and resulted in high patient satisfaction. The sizable proportion of local patients may indicate that teleneurology provides important access for reasons beyond travel distance. Conclusion: This study demonstrates the feasibility of implementing outpatient teleneurology services.

The coronavirus disease 2019 (COVID-19) pandemic has catalyzed the rapid adoption of telemedicine which encompasses synchronous and asynchronous interactions between patients and providers. In order to facilitate this rapid deployment, there has been numerous regulatory changes to ensure caregivers can effectively communicate with patients during this time. We illustrate a model where people, processes, and technology work together to address the comprehensive needs of multiple sclerosis (MS) patients. We provide a template for how multidisciplinary, academic practices can implement a rapid shift to virtual management during the pandemic using existing infrastructure that can be widely adopted to care for patients with chronic diseases. Telemedicine was incorporated into our entire practice, which encompasses neurology, rehabilitation, advanced practice providers, fellows, social work, and behavioral medicine. Our patient satisfaction results remained stable across almost all domains when compared to survey results from our typical, in-office visits. Our experience demonstrates telemedicine's transformative potential in successfully managing a multidisciplinary MS clinic during the time of a pandemic and outlines a potential path for other practices to follow., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Cattle feedyards are animal feeding operations where beef cattle are finished to market weight on grain. Cattle feeding can be dirty, demanding, and dangerous work. This study sought to assess the predictors of fatigue and the need for recovery among Latino/a immigrant cattle feedyard workers in the United States. A path model was examined to explore direct and indirect relations among physical fatigue, mental fatigue, need for recovery, job characteristics, and health and sociodemographic covariates. Lower self-reported health, experiencing physical pain, not handling animals, and decreased decision latitude were directly related to increased physical fatigue. Shorter tenure working on cattle feedyards, lower educational level, experiencing physical pain, and increased job demands were directly related to heightened mental fatigue. Being female, experiencing physical pain, an elevated average of hours worked per day, increased job demands, and less decision latitude were directly related to an increased need for recovery and indirectly related to both physical and mental fatigue. Physical and mental fatigue have specific correlates, but job characteristics, including job demands and decision latitude, can directly and indirectly impact workers' levels of physical and mental fatigue and their need for recovery. Both preventive measures and restructuring work operations may reduce the risk for fatigue and the need for recovery. Implications for cattle feedyard workers, supervisors, and employers are discussed. Finding ways to balance productivity and the well-being of workers should be a high priority for cattle feedyards across the country.

Competing Interests: Competing interests: None declared.

An emerging corpus of research seeks to use virtual realities (VRs) to understand the neural mechanisms underlying spatial navigation and decision making in rodents. These studies have primarily used visual stimuli to represent the virtual world. However, auditory cues play an important role in navigation for animals, especially when the visual system cannot detect objects or predators. We have developed a virtual reality environment defined exclusively by free-field acoustic landmarks for head-fixed mice. We trained animals to run in a virtual environment with 3 acoustic landmarks. We present evidence that they can learn to navigate in our context: we observed anticipatory licking and modest anticipatory slowing preceding the reward region. Furthermore, we found that animals were highly aware of changes in landmark cues: licking behavior changed dramatically when the familiar virtual environment was switched to a novel one, and then rapidly reverted to normal when the familiar virtual environment was re-introduced, all within the same session. Finally, while animals executed the task, we performed in-vivo calcium imaging in the CA1 region of the hippocampus using a modified Miniscope.org system. Our experiments point to a future in which auditory virtual reality can be used to expand our understanding of the neural bases of audition in locomoting animals and the variety of sensory cues which anchor spatial representations in a new virtual environment.

We uncover a topological classification applicable to open fermionic systems governed by a general class of Lindblad master equations. These "quadratic Lindbladians" can be captured by a non-Hermitian single-particle matrix which describes internal dynamics as well as system-environment coupling. We show that this matrix must belong to one of ten non-Hermitian Bernard-LeClair symmetry classes which reduce to the Altland-Zirnbauer classes in the closed limit. The Lindblad spectrum admits a topological classification, which we show results in gapless edge excitations with finite lifetimes. Unlike previous studies of purely Hamiltonian or purely dissipative evolution, these topological edge modes are unconnected to the form of the steady state. We provide one-dimensional examples where the addition of dissipators can either preserve or destroy the closed classification of a model, highlighting the sensitivity of topological properties to details of the system-environment coupling.

Competing Interests: Declaration of Competing Interest CMA and MDW have nothing to declare, JJF has participated on Consulting and Advisory Boards for Sanofi and has received a Sylvia Lawry fellowship grant from National Multiple Sclerosis Society, MM has participated on Consulting and Advisory Boards for Genzyme and Genetech and has received a Slyvia Lawry grant from NMSS. DO has received research support from National Multiple Sclerosis Society, National Institutes of Health, Patient Centered Research Institute, Race to Erase MS Foundation, Genentech, and Genzyme. He has also received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Novartis and Merck. ET reports personal consulting fees and support to attend educational meetings from Roche, support to attend educational meetings from Merck and Novartis. ET received salary from Biogen as part of a MS Registry Fellowship, and currently contributes to work in a joint-working research study funded by Novartis. NE has received honoraria and advisory fees from Merck, Novartis, Roche, Biogen and Genzyme.

We investigate how information spreads in three paradigmatic one-dimensional models with spatial disorder. The models we consider are unitarily related to a system of free fermions and, thus, are manifestly integrable. We demonstrate that out-of-time-order correlators can spread slowly beyond the single-particle localization length, despite the absence of many-body interactions. This phenomenon is shown to be due to the nonlocal relationship between elementary excitations and the physical degrees of freedom. We argue that this nonlocality becomes relevant for time-dependent correlation functions. In addition, a slow logarithmic-in-time growth of the entanglement entropy is observed following a quench from an unentangled initial state. We attribute this growth to the presence of strong zero modes, which gives rise to an exponential hierarchy of time scales upon ensemble averaging. Our work on disordered integrable systems complements the rich phenomenology of information spreading and we discuss broader implications for general systems with nonlocal correlations.

We study the topological properties of one-dimensional systems undergoing unitary time evolution. We show that symmetries possessed both by the initial wave function and by the Hamiltonian at all times may not be present in the time-dependent wave function-a phenomenon which we dub "dynamically induced symmetry breaking." This leads to the possibility of a time-varying bulk index after quenching within noninteracting gapped topological phases. The consequences are observable experimentally through particle transport measurements. With reference to the entanglement spectrum, we explain how the topology of the wave function can change out of equilibrium, both for noninteracting fermions and for symmetry-protected topological phases protected by antiunitary symmetries.

While previous research has established links among multiple aspects of parenting, empathy, and prosocial behaviors in youth, little is known regarding the relations between helicopter parenting, a particular type of parental over control, and empathy and prosocial behaviors (Padilla-Walker, 2014). Because helicopter parenting could undermine empathic and prosocial outcomes by negatively impacting self-regulatory behaviors and promoting narcissistic tendencies (Padilla-Walker, 2014; Segrin, Woszidlo, Givertz, Bauer, & Murphy, 2012; Segrin, Woszidlo, Givertz, & Montgomery, 2013), the author sought to examine potential relationships among these constructs. A battery of self-report measures was administered to an emerging adult sample (N = 187 college students; 49% women; M age = 18.81 years; 71% White). Hierarchical multiple regression model results indicated that both maternal and paternal helicopter parenting predicted fewer positive prosocial and empathic outcomes, and these relations depended on parental attachment, gender, and specific outcome assessed. Helicopter parenting appears to be a distinct type of parental overcontrol that especially contributes to moral development.