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Phase curves of asteroids are typically considered to depend solely on the scattering properties of airless particulate surfaces and the size of the object being studied. In this study, we demonstrate the additional dependence of phase curves on object shape, rotation pole orientation, and viewing geometry over an apparition. Variations in the phase curve of near-Earth asteroid (159402) 1999 AP10 over its apparition from 2020 July to 2021 January are verified to be due to aspect changes over the apparition. This is achieved through shape modelling of the asteroid and simulation of the phase curve over the apparition. We present simulations of asteroid phase curves over a range of geometries to understand the potential magnitude of this aspect effect, and under which circumstances it can begin to dominate in the phase curves. This dependence on aspect may introduce significant additional uncertainty in the properties derived from phase-curve data. We provide and demonstrate software code to estimate the aspect-related uncertainty in near-Earth asteroid phase curves through simulation and model fitting of a randomly generated sample of ellipsoidal asteroid models over the observed viewing geometry. We demonstrate how ignoring this effect may lead to misleading interpretations of the data and underestimation of uncertainties in further studies, such as those in the infrared that use phase curve derived parameters when fitting physical properties of an asteroid. [ABSTRACT FROM AUTHOR]

Background: People of African and Caribbean heritage in the UK have a higher prevalence of Type 2 Diabetes (T2D) and poorer health outcomes than white Europeans. Healthy Eating and Active Lifestyles for Diabetes Online (HEAL-D Online) is a co-designed, culturally tailored T2D self-management programme for black African and Caribbean adults, which, due to online delivery, is well positioned for spread. This qualitative evaluation uses the Exploration-Preparation-Implementation-Sustainment (EPIS) framework to explore factors affecting scale-up from delivery and commissioning perspectives., Methods: Semi-structured interviews were conducted with nine commissioners and providers of T2D services from three English areas with varying population characteristics to explore scale-up. Focus groups were held with 15 people of African and Caribbean heritage with T2D lived experience to explore the impact of a digital model of participation. Data were analysed using thematic analysis, with themes mapped onto the EPIS framework exploration phase constructs to consider the outer and inner contextual factors for planning implementation., Results: Six EPIS constructs were identified by commissioners and providers as key in scaling HEAL-D Online. People with T2D lived experience explored the online mode of delivery, using the patient advocacy construct as the analytical lens. In delivering an online T2D programme, two themes were identified: (1) aligning course content with people's preferences; (2) practicalities to ensure online delivery was acceptable and accessible to the community., Conclusions: HEAL-D Online was acceptable with the potential to help address health inequalities. The EPIS framework provided a structure to understand factors in planning scale-up for an intervention targeting underserved communities., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Purpose: Children with typical hearing and various language and cognitive challenges can struggle with processing speech in background noise. Thus, children with a language disorder (LD) are at risk for difficulty with speech recognition in poorer acoustic environments., Method: The current study compared the effects of background speech-shaped noise (SSN) with and without reverberation on sentence recognition for children with LD ( n = 9) and typical language development (TLD; n = 9). We also investigated whether the use of a remote microphone (RM) improved speech recognition for children with LD., Results: Children with LD demonstrated poorer sentence recognition than peers with TLD in SSN. Both groups had poorer sentence recognition with SSN + reverberation than SSN alone. Notably, using an RM improved speech recognition for children with LD in SSN and SSN + reverberation., Conclusion: We discuss educational implications and future research questions to identify how to optimally support speech recognition in noisy environments for children with LD., Supplemental Material: https://doi.org/10.23641/asha.28037984.

Objectives: To assess the feasibility and acceptability of delivering Healthy Eating and Active Lifestyles for Diabetes (HEAL-D) Online., Intervention: HEAL-D Online-a 7-week culturally tailored type 2 diabetes educational programme delivered using online platform., Setting: Programme delivered by a London NHS trust, with patients referred from primary care healthcare professionals via a central booking system., Participants: 53 HEAL-D service users completed a postcourse questionnaire, and 14 service users and 7 service delivery staff participated in interviews., Design: Mixed methods service evaluation., Primary and Secondary Outcomes: Service user engagement, acceptability and perceived patient benefit assessed using service activity data. Feasibility and acceptability of HEAL-D Online, using semi-structured interviews to explore the views and experiences of service users and service delivery staff., Results: Service activity data showed that initial uptake of HEAL-D Online was good (62% attendance) with a high adherence to the programme (77% completion). A high fidelity (94%) was observed, and qualitative findings showed that staff and service users were satisfied with all aspects of course delivery. Both service activity and qualitative data indicated that attendees felt more confident in controlling their diet and managing their diabetes post-HEAL-D Online., Conclusion: This evaluation demonstrates the feasibility of delivering HEAL-D using an online platform, with its ability to achieve similar goals compared with its face-to-face counterpart. Challenges were identified around the identification, recruitment and referral of eligible patients into the programme, which need to be addressed for successful implementation on a wider scale., Competing Interests: Competing interests: NS is the director of London Safety and Training Solutions, which offers training and improvement and implementation solutions to healthcare organisations and the pharmaceutical industry. JTSL, SL, LMG, SI, OB, NC and AW have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4 + T cell responses, and HA-specific CD8 + T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ + CD4 + T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies., (© 2024. The Author(s).)

Background: Psoriasis is an inflammatory skin condition where immune cells play a significant role. The importance of the cross-talk between keratinocytes and immune cells in the pathogenesis of psoriasis has recently been reaffirmed. Recent studies have found that several S1PR functional antagonists, other than S1PR2, are effective in improving psoriasis. This study aims to investigate the role of S1PR2 in psoriasis, that has not been investigated before., Methods: Spatial transcriptomics, RT-qPCR, and flow cytometry were used to map the immune cell landscape and its association with metabolic pathways in an imiquimod (IMQ)-induced psoriasis-like inflammation in S1pr2 fl/fl K14-Cre mice that could not sense sphingosine-1-phosphate (S1P) in the epidermis through the S1PR2 receptor., Results: Our analysis suggests that S1PR2 in keratinocytes plays a major role in psoriasis-like inflammation compared to other S1PRs. It acts as a down-regulator, inhibiting the recruitment of Th17 cells into the skin. In IMQ-induced psoriasis skin, both S1pr2 -/- and S1pr2 fl/fl K14-Cre mice showed higher expressions of proinflammatory cytokines such as TNF-α, IL-17A, and IL-1β together with higher expressions of MyD88/NF-κB pathway compared to the wild-type mice. Remarkably, in IMQ-treated mice, the deletion of S1pr2 in keratinocytes only resulted in a larger population of Th17 cells in skin-draining lymph nodes. Other S1PR modulators did not improve the worsening of psoriasis-like inflammation caused by S1PR2 deficiency in keratinocytes., Conclusion: This study reaches two main conclusions: signals from keratinocytes play a central role in creating an immune environment that promotes the development of psoriasis, and stimulating S1PR2, instead of suppressing it, represents a potential therapeutic approach for psoriasis., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Masuda-Kuroki, Alimohammadi, Lowry and Di Nardo.)

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes . The following article describes a quality improvement project focused on increasing the use of continuous glucose monitoring among emerging adults with type 1 diabetes enrolled in a health care transition program in the state of Washington., Competing Interests: I.B.H. has served as an independent consultant for Abbott, Hagar, and Roche separate from this work and has received research funding from Dexcom and Tandem. No other potential conflicts of interest relevant to this article were reported., (© 2024 by the American Diabetes Association.)

Fundamental to the quality of life is assisting patients in relieving pain including at the end of life. Compassionate, effective, evidence-based pain care for the dying improves the quality of life for patients and may reduce distress and complicated bereavement in the loved ones witnessing this death. However, efforts designed to mitigate the consequences of the opioid epidemic have seriously compromised pain care at the end of life. This has created an urgent need to focus on the barriers to relief, and solutions necessary to provide safe and effective pain and symptom management in this population. To that end, a committee of experts was convened by the American Society for Pain Management Nursing and the Hospice and Palliative Nursing Association. These experts reviewed the current literature, developed a draft position statement which underwent consecutive revisions. This statement was then endorsed by the respective organizations. Elucidation of barriers to effective pain control in advanced disease allows targeted interventions; including those related to clinical care, education, accessibility, and research. As nurses, we must continuously advocate for humane and dignified care, promoting ethical, effective pain and symptom management at the end of life for all., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Valley Fever is a respiratory disease caused by inhalation of arthroconidia, a type of spore produced by fungi within the genus Coccidioides spp. which are found in dry, hot ecosystems of the Western Hemisphere. A quantitative microbial risk assessment (QMRA) for the disease has not yet been performed due to a lack of dose-response models and a scarcity of quantitative occurrence data from environmental samples. A literature review was performed to gather data on experimental animal dosing studies, environmental occurrence, human disease outbreaks, and meteorological associations. As a result, a risk framework is presented with information for parameterizing QMRA models for Coccidioides spp., with eight new dose-response models proposed. A probabilistic QMRA was conducted for a Southwestern US agricultural case study, evaluating eight scenarios related to farming occupational exposures. Median daily workday risks for developing severe Valley Fever ranged from 2.53 × 10 -7 (planting by hand while wearing an N95 facemask) to 1.33 × 10 -3 (machine harvesting while not wearing a facemask). The literature review and QMRA synthesis confirmed that exposure to aerosolized arthroconidia has the potential to result in high attack rates but highlighted that the mechanistic relationships between environmental conditions and disease remain poorly understood. Recommendations for Valley Fever risk assessment research needs in order to reduce disease risks are discussed, including interventions for farmers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kerry Hamilton and other faculty at QMRA workshop (Charles Haas) reports financial support and travel were provided by NIH., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA's F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600  ms - 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes - B1, provided by the Japanese space agency, JAXA, and B2 - that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission's science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Diversity across algal family Symbiodiniaceae contributes to the environmental resilience of certain coral species. Chlorophyll- a fluorescence measurements are frequently used to determine symbiont health and resilience, but more work is needed to refine these tools and establish how they relate to underlying cellular traits. We examined trait diversity in symbionts from the generas Cladocopium and Durusdinium, collected from 12 aquacultured coral species. Photophysiological metrics (Φ PSII , σ PSII , ρ, τ 1 , τ 2 , antenna bed quenching, non-photochemical quenching, and qP) were assessed using a prototype multi-spectral fluorometer over a variable light protocol which yielded a total of 1,360 individual metrics. Photophysiological metrics were then used to establish four unique light-response phenotypic variants. Corals harboring C15 were predominantly found within a single light-response phenotype which clustered separately from all other coral fragments. The majority of Durusdinium dominated colonies also formed a separate light-response phenotype which it shared with a few C1 dominated corals. C15 and D1 symbionts appear to differ in which mechanisms they use to dissipate excess light energy. Spectrally dependent variability is also observed across light-response phenotypes that may relate to differences in photopigment utilization. Symbiont cell biochemical and structural traits (atomic C:N:P, cell size, chlorophyll- a , neutral lipid content) was also assessed within each sample and differ across light-response phenotypes, linking photophysiological metrics with underlying primary cellular traits. Strong correlations between first- and second-order traits, such as Quantum Yield and cellular N:P content, or light dissipation pathways (qP and NPQ) and C:P underline differences across symbiont types and may also provide a means for using fluorescence-based metrics as biomarkers for certain primary-cellular traits., Competing Interests: Author TM was employed by Reef Systems Coral Farm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 McQuagge, Pahl, Wong, Melman, Linn, Lowry and Hoadley.)

Background: Partial edentulism in growing children due to aplasia or trauma poses a difficult situation to manage. We present a case of horizontal ridge augmentation in a growing patient who had trauma in childhood when it was too early to place implants., Methods and Results: This patient had a history of trauma, at age 13, that resulted in mandibular fracture and loss of teeth #23-27. The definitive restorative treatment plan was postponed due to the patient's continued growth. At age 18, horizontal bone augmentation was performed in a severely resorbed anterior mandible. After 7 months of healing, 7-8 mm ridge augmentation was achieved, and three implants were placed. Soft tissue augmentation by free gingival graft was performed at implant second stage surgery 4 months later., Conclusions: When considering the timing of implant placement in adolescents, the clinician walks a fine line between waiting as long as possible to place the implants and racing against continued resorption of the edentulous alveolar ridge. 70/30 mineralized/demineralized cortical bone allograft and injectable platelet-rich fibrin mix combined with tenting screws and resorbable membranes are useful measures for horizontal ridge augmentation in growing patients., Key Points: Why is this case new information? There are insufficient data available when considering implant treatment in younger patients. The present case was managed with a variation of the sausage technique described by Urban. The use of allograft, I-PRF, and tenting screws replaced the use of autogenous bone and resulted in exceptional results. What are the keys to the successful management of this case? Delaying treatment until after the critical growth period has passed. Adequate flap release, tension-free primary flap closure, and space maintenance through the use of tenting screws and tacking the membranes using tacking pins provided support for the grafted site. What are the primary limitations to success in this case? The continued growth may cause infra occlusion of the implant-supported bridge., (© 2022 American Academy of Periodontology.)

Objectives: Previous research has shown racial, ethnic, and socioeconomic disparities in provider medical evaluations and reporting to child protective services (CPS) and law enforcement (LE) for cases of suspected child physical abuse. Our hospital standardized evaluation and reporting of high-risk bruising using a clinical pathway. We aimed to assess whether standardization impacted disparity., Methods: We performed a retrospective observational study including children evaluated in the emergency department who had a social work consult for concern for child abuse or neglect between June 2012 and December 2019. From this group, we identified children with high-risk bruising. We compared outcomes (receipt of skeletal survey, CPS report, or LE report) before and after implementation of a standard bruising evaluation pathway to determine how the intervention changed practice among various racial, ethnic, and socioeconomic groups., Results: During the study period, 2129 children presented to the ED and received a social work consult for child abuse or neglect. Of these, 333 had high-risk bruising. Children without private insurance had a higher risk of having a CPS (adjusted relative risk, 1.32; 95% confidence interval, 1.09-1.60) or LE (adjusted relative risk, 1.48; 95% confidence interval, 1.11-1.97) report prepathway, but not after pathway implementation. No significant associations were seen for race or ethnicity., Conclusions: A standardized clinical pathway for identification and evaluation of high-risk bruising may help to decrease socioeconomic disparities in reporting high-risk bruising. Larger studies are needed to fully evaluate disparities in assessment and reporting of child abuse., Competing Interests: Disclosure: Drs. Crumm, Brown, and Schlatter provide consultation and testimony in child abuse cases. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Off-label intravenous (IV) route of anakinra is increasingly recognized to enable higher and faster maximal plasma concentrations than subcutaneous route for treatment of cytokine storm syndromes. Objective: To describe off-label indications of IV anakinra, corresponding dosing and safety profiles, particularly during the coronavirus disease 19 (COVID-19) pandemic. Methods: A retrospective, single-cohort study was conducted at an academic medical center to evaluate use of IV anakinra in hospitalized pediatric patients (age ≤21 years). Institutional Review Board review was considered exempt. The primary endpoint was the primary indication(s) for IV anakinra. The key secondary endpoints were dosing of IV anakinra, previous immunomodulatory therapies, and adverse events. Results: Of 14 pediatric patients, 8 (57.1%) received IV anakinra for treatment of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, whereas 3 and 2 were treated for hemophagocytic lymphohistiocytosis (HLH) and flares of systemic onset juvenile idiopathic arthritis (SoJIA), respectively. The initial dosing regimen of IV anakinra for MIS-C associated with COVID-19 was a median dose of 2.25 mg/kg/dose with a median dosing interval of 12 hours for a median initial treatment duration of 3.5 days. Eleven (78.6%) patients received previous immunomodulatory therapies (IV immune globulin [n = 10; 71.4%] and steroids [n = 9; 64.3%]). No adverse drug events were documented. Conclusion: IV anakinra was used off-label for treatment of MIS-C associated with COVID-19, HLH and SoJIA flares in critically ill patients with no adverse drug events documented. This study helped ascertain the off-label indications of IV anakinra and corresponding patient characteristics., Competing 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) 2023.)

Human norovirus (HuNoV) is an important cause of acute gastroenteritis and can be transmitted by water exposures, but its persistence in water is not well understood. Loss of HuNoV infectivity in surface water was compared with persistence of intact HuNoV capsids and genome segments. Surface water from a freshwater creek was filter-sterilized, inoculated with HuNoV (GII.4) purified from stool, and incubated at 15 or 20 °C. We measured HuNoV infectivity via the human intestinal enteroid system and HuNoV persistence via reverse transcription-quantitative polymerase chain reaction assays without (genome segment persistence) or with (intact viral capsid persistence) enzymatic pretreatment to digest naked RNA. For infectious HuNoV, results ranged from no significant decay to a decay rate constant ( "k ") of 2.2 day -1 . In one creek water sample, genome damage was likely a dominant inactivation mechanism. In other samples from the same creek, loss of HuNoV infectivity could not be attributed to genome damage or capsid cleavage. The range in k and the difference in the inactivation mechanism observed in water from the same site could not be explained, but variable constituents in the environmental matrix could have contributed. Thus, a single k may be insufficient for modeling virus inactivation in surface waters.

Objectives: Determine whether Pre-Game Safety Huddles, a novel and low-resource approach to concussion education, increase the expected likelihood of concussion reporting for youth athletes., Methods: A cluster-randomised trial compared Safety Huddles to usual care. Safety Huddles bring together athletes and coaches from both teams before the start of each game for coaches to briefly affirm the importance of speaking up if a concussion is suspected. Participants were athletes from 22 competitive community-based American football and girls and boys soccer teams (ages 9-14), and randomisation into intervention or control occurred at the level of the bracket (group of teams that compete against each other during the regular season). The primary outcome was expected likelihood of reporting concussion symptoms to the coach, measured via validated athlete survey at the beginning and end of the season., Results: Of 343 eligible participants, 339 (99%) completed baseline surveys and 303 (88%) completed surveys at season end. The mean (SD) age was 11.4 (1.1) years, 26% were female soccer athletes, 27% were male soccer athletes and 47% were football athletes. In adjusted analyses accounting for baseline values and clustering by sport and team via random effects, expected likelihood of concussion reporting at the end of the season was significantly higher in the intervention group compared to controls (mean difference=0.49, 95% CI 0.11 to 0.88; Cohen's d=0.35)., Conclusions and Relevance: Pre-Game Safety Huddles increased the expected likelihood of athletes reporting concussion symptoms. While further study is warranted, sport organisations should consider this approach a promising low-resource option for improving concussion safety in their setting., Trial Registration Number: NCT04099329., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The National Health Service Insight Prioritisation Programme was established to accelerate the implementation and evaluation of innovation that supports post-pandemic working. Supporting this, the Academic Health Science Network and National Institute for Health and Care Research Applied Research Collaboration in South London are testing and evaluating the implementation and scale-up of a type 2 diabetes (T2D) intervention.T2D is estimated to be three times more prevalent in UK African and Caribbean communities than in white Europeans. To tackle ethnic inequities in T2D healthcare access, an evidence-based, culturally tailored self-management and education programme for African and Caribbean adults (Healthy Eating & Active Lifestyles for Diabetes, HEAL-D) has been codeveloped with people with lived experience. Initially a face-to-face programme, HEAL-D pivoted to virtual delivery in response to COVID-19.The purpose of this study is to explore the (1) feasibility and acceptability of a virtual delivery model for HEAL-D in south London and (2) factors affecting its scale-up across other areas in England., Methods and Analysis: The study will have two strands: (1) mixed-methods prospective evaluation of HEAL-D virtual delivery in south London using routinely collected service-level data, service delivery staff and service user interviews and observations; and (2) prospective qualitative study of the scale-up of this virtual delivery comprising interviews and focus groups with members of the public, and diabetes services commissioners and providers across England. Qualitative data will be analysed using thematic analysis. Quantitative analysis will use descriptive statistics and reporting summary tables and figures. The study will be grounded in well-established implementation frameworks and service user involvement., Ethics and Dissemination: 'Minimal Risk Registration' ethical clearance was granted by King's College London's Research Ethics Office (ref: MRA-21/22-28498). Results will be published in a peer-reviewed journal and summaries provided to the study funders and participants., Competing Interests: Competing interests: NS is the director of the London Safety and Training Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to healthcare organisations. LG is involved in the delivery of the HEAL-D programme that is being evaluated in this research. The other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vanishing bile duct syndrome (VBDS) is a serious cholestatic liver disease that can be a complication of drug-induced liver injury (DILI). While journals have published case reports of this condition, large studies on a cohort of these patients are lacking. We aimed to compile published case reports and case series of patients with VBDS and DILI to describe the clinical and laboratory characteristics of the disease and identify factors associated with good and poor outcomes., Methods: We included case reports and case series of VBDS secondary only to DILI. We extracted demographic, clinical, laboratory, treatment, and exposure data from each case report and categorized cases by outcome, good versus poor. We defined poor outcomes as cases with severe long-term complications or death. We analyzed risk factors for poor outcomes using logistic regression., Results: We identified a total of 59 eligible cases. Of those, 39 (59%) were female, the median age was 36 (IQR:12-58), and 18 (31%) were pediatric cases (≤18 years). The most common offending drug class was antibiotics, especially beta-lactams. Patients with increased total bilirubin (OR=4.69; 95% CI=1.55-15.49; p = 0.008), increased direct bilirubin (OR=6.50; 95% CI=1.34-48.91; p = 0.034), lower liver synthetic activity (OR=0.11; 95% CI=0.02-0.55; p = 0.013), and older age (OR=3.31; 95% CI=1.15-10.04; p = 0.029) were more likely to develop poor outcomes., Conclusions: In patients with VBDS and DILI, antibiotics were the most common offending agents. Higher total and direct bilirubin levels were associated with poor outcomes., Competing Interests: Declaration of interests The authors declare no financial or personal conflicts of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Aerosol transport of enteric microbiota including fecal pathogens and antimicrobial resistance genes (ARGs) has been documented in a range of settings but remains poorly understood outside indoor environments. We conducted a systematic review of the peer-reviewed literature to summarize evidence on specific enteric microbiota including enteric pathogens and ARGs that have been measured in aerosol samples in urban settings where the risks of outdoor exposure and antibiotic resistance (AR) spread may be highest. Following PRISMA guidelines, we conducted a key word search for articles published within the years 1990-2020 using relevant data sources. Two authors independently conducted the keyword searches of databases and conducted primary and secondary screenings before merging results. To be included, studies contained extractable data on enteric microbes and AR in outdoor aerosols regardless of source confirmation and reported on qualitative, quantitative, or viability data on enteric microbes or AR. Qualitative analyses and metric summaries revealed that enteric microbes and AR have been consistently reported in outdoor aerosols, generally via relative abundance measures, though gaps remain preventing full understanding of the role of the aeromicrobiological pathway in the fate and transport of enteric associated outdoor aerosols. We identified remaining gaps in the evidence base including a need for broad characterization of enteric pathogens in bioaerosols beyond bacterial genera, a need for greater sampling in locations of high enteric disease risk, and a need for quantitative estimation of microbial and nucleic acid densities that may be applied to fate and transport models and in quantitative microbial risk assessment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Of the 80% people with psychosis living in low- and middle-income countries (LMICs), up to 90% are left to the care of families. The World Health Organization has recommended the inclusion of families in community-based rehabilitation and while there is evidence of its implementation in LMICs, this has not been reviewed yet. This study aims to describe the key features and implementation strategies of family-based interventions in LMICs, and appraise their effectiveness., Methods: Included are people with psychosis in LMICs who receive any form of family-based intervention, compared to their usual or absence of treatment, with patient outcome measures. We searched (August 2021) through Embase, MEDLINE, Global Health, PsycInfo, Social Policy and Practice, and Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as from grey literature and hand-searched records. Risk of bias was assessed through the Integrated Quality Criteria for Review of Multiple Study Designs (ICROMS) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS), then analyzed narratively., Results: 27 studies were included from the 5254 records. Psychotherapeutic features, systems approach and task-sharing were key intervention elements. Delivery strategies included preliminary research, sustained family engagement, and cultural adaptation. There were positive health impacts across four outcome domains., Conclusion: All studies recommended family-based interventions, with limitations in heterogeneity and 70% of them rated high risk of bias., Other: Review was registered in PROSPERO (CRD42021256856). The authors did not receive funding for this research., (© 2022. The Author(s).)

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P  = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Patients with cancer are living longer, and many experience pain secondary to tumor invasion or as a consequence of cancer-directed therapies. Opioid use disorders and associated morbidity and mortality have increased with dramatic rise during the SARS-CoV-2 pandemic. National and international stakeholders have developed clinical practice guidelines in an effort to curb opioid misuse and overdose-related death. However, to ensure that patients with cancer do not experience barriers to adequate pain management, most of these guidelines are not intended for patients with cancer-related pain or for those receiving palliative or hospice care. Oncology, palliative, and hospice care providers are increasingly tasked with the management of severe disease-related pain in the setting of coexisting opioid use disorder without research on the most effective risk and harm reduction strategies to guide care. Clinicians should be familiar with addiction medicine and chronic pain literature and be able to incorporate some of these best practices. This case study reviews the management of severe cancer-related pain in a patient with co-occurring opioid use disorder, utilizing many of the best practices in available clinical practice guidelines for the management of chronic non-cancer-related pain., Competing Interests: The author has no conflicts of interest to disclose., (Copyright © 2022 by The Hospice and Palliative Nurses Association. All rights reserved.)

This paper presents a local planning approach that is targeted for pseudo-omnidirectional vehicles: that is, vehicles that can drive sideways and rotate on the spot. This local planner-MSDU-is based on optimal control and formulates a non-linear optimization problem formulation that exploits the omni-motion capabilities of the vehicle to drive the vehicle to the goal in a smooth and efficient manner while avoiding obstacles and singularities. MSDU is designed for a real platform for mobile manipulation where one key function is the capability to drive in narrow and confined areas. The real-world evaluations show that MSDU planned paths that were smoother and more accurate than a comparable local path planner Timed Elastic Band (TEB), with a mean (translational, angular) error for MSDU of (0.0028 m, 0.0010 rad) compared to (0.0033 m, 0.0038 rad) for TEB. MSDU also generated paths that were consistently shorter than TEB, with a mean (translational, angular) distance traveled of (0.6026 m, 1.6130 rad) for MSDU compared to (0.7346 m, 3.7598 rad) for TEB.

Competing Interests: Declaration of Competing Interest Dr. Mogayzel has received grant funding from Vertex Pharmaceuticals

Objective: To evaluate the relative cost-effectiveness of tildrakizumab and other biologic and targeted systemic treatments compared with a mix of topical therapies, phototherapies, and other conventional systemic therapies as first-line treatment for moderate-to-severe plaque psoriasis from a United States payer's perspective., Methods: A Markov model consisting of health states based on Psoriasis Area Severity Index (PASI) response rate categories and death was developed. The probabilities of achieving PASI responses were derived from a network meta-analysis based on published efficacy data. Health care costs and effectiveness measured in quality-adjusted life-years (QALYs) were estimated. Incremental costs per QALY gained of each biologic/targeted first-line treatment versus a mix of conventional treatments were compared to provide relative cost-effectiveness among biologic and targeted first-line treatments., Results: Over 10 years, the incremental cost per QALY gained compared with a mix of topical therapies, phototherapies, and other oral systemic therapies was lowest for brodalumab, infliximab, apremilast, and tildrakizumab, followed by secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept. The position of tildrakizumab relative to the other treatments remained the same across multiple scenarios., Conclusions: Tildrakizumab is among the most cost-effective first-line therapies for moderate-to-severe plaque psoriasis and is more cost-effective than secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept.