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Abstract Omaveloxolone is a nuclear factor (erythroid‐derived 2)‐like 2 activator approved in the United States and the European Union for the treatment of patients with Friedreich ataxia aged ≥16 years, with a recommended dosage of 150 mg orally once daily on an empty stomach. The effect of the US Food and Drug Administration (FDA) high‐fat breakfast on the pharmacokinetic profile of omaveloxolone observed in study 408‐C‐1703 (NCT03664453) deviated from the usual linear correlation between fed/fasted maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) ratios reported for various oral drugs across 323 food effect studies. Here, physiologically based biopharmaceutics modeling (PBBM) was implemented to predict and explain the effect of the FDA high‐fat breakfast on a 150‐mg dose of omaveloxolone. The model was developed and validated based on dissolution and pharmacokinetic data available across dose‐ranging, food effect, and drug–drug interaction clinical studies. PBBM predictions support clinical observations of the unique effect of a high‐fat meal on omaveloxolone pharmacokinetic profile, in which the Cmax increased by 350% with only a 15% increase in the AUC. Key parameters influencing omaveloxolone pharmacokinetics in the fasted state based on a parameter sensitivity analysis included bile salt solubilization, CYP3A4 activity, drug substance particle size distribution, and permeability. Mechanistically, in vivo omaveloxolone absorption was solubility and dissolution rate limited. However, in the fed state, higher bile salt solubilization led to more rapid dissolution with predominant absorption in the upper gastrointestinal tract, resulting in increased susceptibility to first‐pass gut extraction; this accounts for the lack of correlation between Cmax and AUC for omaveloxolone.

Abstract Healthcare requires practitioners to successfully negotiate boundaries between communities of practice (CoP) in a clinical landscape of practice (LoP), with development of interprofessional identity important in promoting successful interprofessional collaboration. Interprofessional education (IPE) centered around acute hospital inpatients offers a potential pathway to encourage boundary negotiation and interprofessional identity development. This study aimed to explore interprofessional student teams and their interactions with patients in an acute hospital setting, while investigating if such interactions encouraged interprofessional collaboration and the development of an interprofessional identity. Pivoting around acute hospital inpatients, four interprofessional workshops occurred involving senior medicine, nursing and physiotherapy students. We utilized a concurrent mixed methods design, with qualitative predominating. Qualitative reflexive thematic analysis of post-workshop semi-structured focus groups was supported by quantitative investigation using a validated pre-test post-test international socialisation and valuing scale. Using the landscapes of practice theory lens, we noted that the central role of acute hospital inpatients in the IPE workshops enabled healthcare students to develop knowledgeability of the clinical LoP, in line with the three modes of identification of LoP, namely Engagement, Imagination and Alignment. Following the IPE workshops, where acute inpatients played the pivotal role, students demonstrated a statistically significant increase in interprofessional collaborative practice in terms of the overall interprofessional socialisation and valuing scale and its subscales of value, ability, and comfort in working with each other. Our findings indicate that IPE centered around acute hospital inpatients is a beneficial and effective way to successfully implement IPE in the undergraduate curriculum.

Abstract Firecrackers are a vital element of cultural festivities that happen worldwide. However, the hazardous by-products they emit have a significant impact on environmental pollution, leading to the greenhouse effect and climate change. Aluminium powder serves as the fuel in the traditional flash powder mixture, nitrate of potassium serves as an oxidizing agent, and sulphur acts as the igniter at exact concentrations. The presence of sulfur in the flash powder mixture is critical as it acts as an igniter, contributing to the formation of sulfur dioxide, which can cause environmental harm. We carried out an experiment employing Sargassum wightii brown seaweed powder as a replacement for sulphur at specific amounts to lessen the effects of sulphur in flash powder. We discovered that Sargassum wightii brown seaweed powder may replace up to 50% of the sulphur significance in the flash powder mixture without impairing the flash powder's traditional performance. Our experiments included impact and friction sensitivity, SEM, and FTIR analyses to evaluate the improved flash powder composition. The results revealed that the modified flash powder mixture SP5 and SP10 emits less emission by 12% and 21%, and produces similar noise performance of 108 and 107 dB(A) to the normal flash powder composition (SP), affirming that the SP10 flash powder is a viable alternative. Moreover, in our relentless pursuit to mitigate the detrimental effects on our environment, we have ingeniously introduced a novel product—the Chinese cracker made from vegetable waste paper. Not only does this innovative solution address concerns regarding land pollution, but it also presents a sustainable approach to consumer goods.

This article describes how, the authors, as members of an action research writing group, responded to a comment about feeling vulnerable in risking bringing their work-in-progress to the group and in giving feedback to colleagues by adopting a cooperative inquiry approach to explore vulnerability and risk in the group. In cooperative inquiry group members act as both co-researcher and co-subject in the inquiry and action. The article describes the evolution of the group and how the topic of exploring risk and vulnerability emerged. The group's exploration is grounded in the theory and practice of cooperative inquiry that gives voice to the group members questioning and reflecting. The article concludes by offering three propositions to enhance the work of writing groups.

Racial microaggressions, or subtle race-based insults are associated with negative consequences for receivers. Institutional racism in education directly influences the dissemination of these transgressions in schools, as school personnel may engage in microaggressive behavior toward each other and their students. Given recent calls to address racism, schools and districts may seek to implement trainings to improve school personnel's understanding of these transgressions and their consequences. As part of the current study, we explored factors that might contribute to school personnel's satisfaction with a microaggression training. Participants completed survey items to assess their colorblind racial attitudes, satisfaction with the workshop, and their perceptions surrounding the need for such trainings. We found that colorblind attitudes and perceptions of necessity predicted satisfaction. Implications and future directions for research are discussed. Impact Statement: Calls to address racial injustice in response to the murders of George Floyd and Breonna Taylor during the summer of 2021 have produced an increase in requests for antiracism workshops and trainings across several organizations and professions. In K-12 schools, these trainings may be beneficial in helping school personnel learn about and address racial microaggressions (race-based insults), which may hinder students' success. Although it is imperative that these conversations take place, it is equally important that we are able to understand how school personnel engage in these trainings to increase the likelihood that their behavior will change because of participation. The goal of this study was to understand factors that contribute to school personnel's satisfaction with a microaggression training.

The current study investigated adolescents' (N = 213) decision finding processes and affective reactions to interactions on social media "via" 29 focus groups. As part of a larger study, adolescents participated in focus groups at two time-points across an academic year while participating in a school-based intervention promoting healthy romantic, interpersonal, and family relationships, job readiness, and financial literacy. Qualitative analyses indicated adolescents' experiences and decisions on social media platforms were informed by their "awareness of audiences", namely who they thought would view their posts and anticipated responses from "friends," "family members," "fans," "creeps," and "potential employers." Comprehensive school-based interventions may serve to effectively develop responsibility more broadly, as well as a specific awareness about online risks and behaviors.

This systematic review aims to describe six types of physical activity interventions utilized with children and young adults ages 5-22 as a treatment for ASD. These interventions include swimming, cycling, neuromuscular training, yoga, sports, and exergaming. This examines the knowledge gaps regarding the details of these interventions via time (sessions, per week, overall length), the severity of ASD in participants (using a 4-point scale), and the outcomes specific to ASD (cognition, social skills, physical fitness, and behavior). A systematic search of peer-reviewed research articles was conducted across five databases focusing on physical activity as an intervention for children and young adults with ASD. From an initial screening of 387 records, 29 of the studies were included in the review. The analysis includes types of intervention, dependent measures, research design, and intervention duration. Types of intervention most studied (swimming, cycling, neuromuscular training, yoga, sports, and exergaming) were further analyzed. All studies found that physical activity as an intervention, improved aspects of physical fitness (endurance, strength, balance), cognition, social skills (language, eye contact, engaging with others), and/or behavior.

Despite increased advocacy and investments in mental health systems globally, there has been limited progress in reducing mental disorder prevalence. In this paper, we argue that meaningful advancements in population mental health necessitate addressing the fundamental sources of shared distress. Using a systems perspective, economic structures and policies are identified as the potential cause of causes of mental ill-health. Neoliberal ideologies, prioritizing economic optimization and continuous growth, contribute to the promotion of individualism, job insecurity, increasing demands on workers, parental stress, social disconnection and a broad range of manifestations well-recognized to erode mental health. We emphasize the need for mental health researchers and advocates to increasingly engage with the economic policy discourse to draw attention to mental health and well-being implications. We call for a shift towards a well-being economy to better align commercial interests with collective well-being and social prosperity. The involvement of individuals with lived mental ill-health experiences, practitioners and researchers is needed to mobilize communities for change and influence economic policies to safeguard well-being. Additionally, we call for the establishment of national mental wealth observatories to inform coordinated health, social and economic policies and realize the transition to a more sustainable well-being economy that offers promise for progress on population mental health outcomes. [phrase omitted] Malgre une meilleure sensibilisation et des investissements accrus dans A pesar del aumento de la promocion y las inversiones en sistemas de salud mental en todo el mundo, los avances en la reduccion de la prevalencia de los trastornos mentales han sido limitados. En este documento, sostenemos que para lograr avances significativos en la salud mental de la poblacion es necesario abordar las fuentes fundamentales de la angustia compartida. Mediante una perspectiva sistemica, las estructuras y politicas economicas se identifican como la posible causa de los problemas de salud mental. Las ideologias neoliberales, que priorizan la optimizacion economica y el crecimiento continuo, contribuyen al fomento del individualismo, la inseguridad laboral, el aumento de las exigencias a los trabajadores, el estres parental, la desconexion social y una gran variedad de manifestaciones bien reconocidas que perjudican la salud mental. Insistimos en la necesidad de que los investigadores y los defensores de la salud mental se impliquen cada vez mas en el discurso de la politica economica para atraer la atencion sobre las implicaciones para la salud mental y el bienestar. Pedimos un cambio hacia una economia del bienestar para alinear mejor los intereses comerciales con el bienestar colectivo y la prosperidad social. Para movilizar a las comunidades en favor del cambio e influir en las politicas economicas con el fin de salvaguardar el bienestar, es necesaria la participacion de personas que han padecido enfermedades mentales, profesionales e investigadores. Ademas, pedimos la creacion de observatorios nacionales de bienestar mental que sirvan de base a las politicas sanitarias, sociales y economicas coordinadas y permitan la transicion a una economia del bienestar mas sostenible, que ofrezca perspectivas de progreso en los resultados de salud mental de la poblacion. [phrase omitted] A pesar del aumento de la promocion y las inversiones en sistemas de salud mental en todo el mundo, los avances en la reduccion de la prevalencia de los trastornos mentales han sido limitados. En este documento, sostenemos que para lograr avances significativos en la salud mental de la poblacion es necesario abordar las fuentes fundamentales de la angustia compartida. Mediante una perspectiva sistemica, las estructuras y politicas economicas se identifican como la posible causa de los problemas de salud mental. Las ideologias neoliberales, que priorizan la optimizacion economica y el crecimiento continuo, contribuyen al fomento del individualismo, la inseguridad laboral, el aumento de las exigencias a los trabajadores, el estres parental, la desconexion social y una gran variedad de manifestaciones bien reconocidas que perjudican la salud mental. Insistimos en la necesidad de que los investigadores y los defensores de la salud mental se impliquen cada vez mas en el discurso de la politica economica para atraer la atencion sobre las implicaciones para la salud mental y el bienestar. Pedimos un cambio hacia una economia del bienestar para alinear mejor los intereses comerciales con el bienestar colectivo y la prosperidad social. Para movilizar a las comunidades en favor del cambio e influir en las politicas economicas con el fin de salvaguardar el bienestar, es necesaria la participacion de personas que han padecido enfermedades mentales, profesionales e investigadores. Ademas, pedimos la creacion de observatorios nacionales de bienestar mental que sirvan de base a las politicas sanitarias, sociales y economicas coordinadas y permitan la transicion a una economia del bienestar mas sostenible, que ofrezca perspectivas de progreso en los resultados de salud mental de la poblacion., Introduction Mental health systems are under-resourced, fragmented, inefficient and unable to meet the demands of the growing burden of mental and substance use disorders. Despite the intensive advocacy and action [...]

Abstract Background Research suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)—the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19. Methods We conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status. Results Among 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4–11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0–8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1–3.6). Irrespective of COVID-19 status, Veterans aged

Abstract Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .

Abstract Background The impact of social frailty on older adults is profound including mortality risk, functional decline, falls, and disability. However, effective strategies that respond to the needs of socially frail older adults are lacking and few studies have unpacked how social determinants operate or how interventions can be adapted during periods requiring social distancing and isolation such as the COVID-19 pandemic. To address these gaps, we conducted a scoping review using JBI methodology to identify interventions that have the best potential to help socially frail older adults (age ≥65 years). Methods We searched MEDLINE, CINAHL (EPSCO), EMBASE and COVID-19 databases and the grey literature. Eligibility criteria were developed using the PICOS framework. Our results were summarized descriptively according to study, patient, intervention and outcome characteristics. Data synthesis involved charting and categorizing identified interventions using a social frailty framework. Results Of 263 included studies, we identified 495 interventions involving ~124,498 older adults who were mostly female. The largest proportion of older adults (40.5%) had a mean age range of 70-79 years. The 495 interventions were spread across four social frailty domains: social resource (40%), self-management (32%), social behavioural activity (28%), and general resource (0.4%). Of these, 189 interventions were effective for improving loneliness, social and health and wellbeing outcomes across psychological self-management, self-management education, leisure activity, physical activity, Information Communication Technology and socially assistive robot interventions. Sixty-three interventions were identified as feasible to be adapted during infectious disease outbreaks (e.g., COVID-19, flu) to help socially frail older adults. Conclusions Our scoping review identified promising interventions with the best potential to help older adults living with social frailty.

One of the most straightforward and affordable ways to produce hydrogen is by alkaline water electrolysis. In order to split water molecules into hydrogen and oxygen, an electrolyser is often subjected to current levels of 1.23V. The electrodes in an electrolytic cell are the primary structural component. The cathode electrode type is the one where hydrogen is created via the reduction reaction between the two types of electrodes. LPG is combined with hydrogen at a 4:1 ratio to lower the combustion energy because hydrogen cannot be used directly in a traditional SI engine due to its higher energy production during combustion. With the aid of a vaporizer unit, the hydrogen and LPG are combined in the necessary ratio. Through the bypass line created on the input manifold before the carburettor, where air is also mixed with the hydrogen-LPG fuel with the A/F ratio of 17:1 (stoichiometric ratio) for complete combustion, the fuel mixture is transported to the engine's combustion chamber. Due to the usage of LPG and hydrogen, full combustion may occur as a result of the production of a blue flame during combustion. Better mixing of the fuel and air can be achieved since the fuel mixture is conveyed in va-por state instead of semi-liquid form as in a conventional SI engine. This approach of using mix fuel (LPG+H2) for con-ventional SI engines can lower nitrogen oxide and hydrocarbon values in the exhaust gas more effectively.

BackgroundClinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined.MethodsWe evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots.ResultsUS ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets.ConclusionsAlthough surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

BackgroundInformation about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited.ObjectiveTo measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.DesignThree retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir.SettingVeterans Health Administration (VHA).ParticipantsNonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.InterventionNirmatrelvir-ritonavir or molnupiravir pharmacotherapy.MeasurementsIncidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days.ResultsEighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants.LimitationThe date of COVID-19 symptom onset for most veterans was unknown.ConclusionNirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals.Primary funding sourceU.S. Department of Veterans Affairs.