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BACKGROUND: Cost is a key outcome in quality and value, but it is often difficult to estimate reliably and efficiently for use in real-time improvement efforts. We describe a method using patient-reported outcomes (PROs), Markov modeling, and statistical process control (SPC) analytics in a real-time cost-estimation prototype designed to assess cost differences between usual care and improvement conditions in a national multicenter improvement collaborative--the IBD Qorus Learning Health System (LHS). METHODS: The IBD Qorus Learning Health System (LHS) collects PRO data, including emergency department utilization and hospitalizations from patients prior to their clinical visits. This data is aggregated monthly at center and collaborative levels, visualized using Statistical Process Control (SPC) analytics, and used to inform improvement efforts. A Markov model was developed by Almario et al to estimate annualized per patient cost differences between usual care (baseline) and improvement (intervention) time periods and then replicated at monthly intervals. We then applied moving average SPC analyses to visualize monthly iterative cost estimations and assess the variation and statistical reliability of these estimates over time. RESULTS: We have developed a real-time Markov-informed SPC visualization prototype which uses PRO data to analyze and monitor monthly annualized per patient cost savings estimations over time for the IBD Qorus LHS. Validation of this prototype using claims data is currently underway. CONCLUSION: This new approach using PRO data and hybrid Markov-SPC analysis can analyze and visualize near real-time estimates of cost differences over time. Pending successful validation against a claims data standard, this approach could more comprehensively inform improvement, advocacy, and strategic planning efforts. [ABSTRACT FROM AUTHOR]

Background and Aim: One of the key components of the O ne Health approach to epidemic preparedness is raising awareness and increasing the knowledge of emerging infectious diseases, prevention, and risk reduction. However, related research can involve significant risks to biosafety and biosecurity. For this purpose, we organized a multidisciplinary biosafety hands-on workshop to inform and increase the knowledge of infectious diseases and risk mitigation. This study aimed to describe the process and outcome of a hands-on biosafety training program using a One Health a pproach across a multidisciplinary and multi-specialty group in Nigeria. Materials and Methods: A face-to-face hands-on training for 48 participants was organized by the West African Center for Emerging Infectious Diseases (WAC-EID) at the Jos University Teaching Hospital, serving as a lead institution for the Nigeria project site. Topics covered included (1) an overview of the WAC-EID research; (2) overview of infection prevention and control; (3) safety in animal handling and restraint, sample collection, and processing; (4) safety in field studies including rodent, bird and bat handling; (5) safety practices in the collection of mosquito and other arthropod vectors; (6) personal protective equipment training (disinfection, donning and doffing); and (7) safety in sample collection, labeling, and transportation. The program was executed using a mixed method of slide presentations, practical hands-on sessions, and video demonstrations. Pre- and post-course evaluation assessments and evaluation measures were used to assess training. Results: A total of 48 trainees participated in this training, with 12 (25%), 16 (33.3%), 14 (29.2%), 6 (12.5%) categorized as ornithology, entomology, mammalogy, and clinical interest groups, respectively. The pass rate for the pre-test was 29.4%, while for the post-test, it was 57.1%, or a 28% improvement. 88.6% of the trainees rated the training as relevant to them. Conclusion: Didactic and hands-on biosafety training is relevant in this era of zoonotic epidemics and pandemic preparedness. During this training program, there was a clear demonstration of knowledge transfer that can change the current practices of participants and improve the safety of infectious diseases research. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that many mosquito species regularly engage in high-altitude windborne migration, but its epidemiological significance was debated. The hypothesis that high-altitude mosquitoes spread pathogens over large distances has not been directly tested. Here, we report for the first time that high-altitude windborne mosquitoes are commonly infected with arboviruses, protozoans, and helminths affecting vertebrates and humans, and provide the first description of this pathogen-vector aerial network. A total of 1,017 female mosquitoes (81.4%, N=1,249) intercepted on nets suspended from helium balloons at altitudes of 120-290 m above ground over Mali and Ghana were screened for infection with arboviruses, plasmodia, and filariae, using pan-genus qPCR analyses followed by sequencing of positive samples. The mosquito fauna collected at altitude comprised 61 species, across 9 genera, dominated by Culex , Aedes , and Anopheles . Infection and infectiousness rates of high-altitude migrant mosquitoes were 7.2% and 4.4% with plasmodia, 1.6% and 0.6% with filariae, 3.5% and 1.1% with flaviviruses, respectively. Nineteen mosquito-borne pathogens were identified, including three arboviruses: dengue, West Nile and M'Poko viruses, 13 putative plasmodia species including Plasmodium matutinum and P. relictum , three filariids, including Pelecitus spp., 27 insect-specific viruses and 5 non-mosquito-borne pathogens (e.g., Trypanosoma theileri ). Confirmed head-thorax (disseminated) infections of multiple pathogens in multiple mosquito species, eg., Culex perexiguus , Coquilletidia metallica , Mansonia uniformis , and Anopheles squamosus provides evidence that pathogens carried by high-altitude windborne mosquitoes are infectious and likely capable of infecting naïve hosts far from their starting location. This traffic of sylvatic pathogens may be key to their maintenance among foci as well as initiating outbreaks away from them.

Background: Most individuals living with Alzheimer's disease and related dementias (ADRD) experience one or more neuropsychiatric symptoms, such as agitation which negatively impacts their quality of life. Adapted dance integrates recorded music and movement that is appropriate for people with cognitive limitations. Adapted dance may be an enjoyable activity for persons living with ADRD and may provide psychological and physical benefits., Objective: The purpose of this pilot study was to assess the feasibility of an adapted dance intervention with persons with ADRD and the impacts of 12 weeks of adapted dancing on agitation, balance, gait, lower extremity strength, and caregiver burden., Methods: This study used an experimental design with repeated measures. Participants with ADRD were randomly assigned to a usual care or adapted line dance group that met 60 min twice a week. At pre-test, 4-, 8-, and 12 weeks of intervention, measures were collected for agitation, balance, gait, lower extremity strength, and caregiver burden., Results: The sample consisted of 4 males and 12 females (n = 16) with ADRD whose age ranged from 69-97 years. Twelve weeks of adapted line dance was found acceptable by ADRD participants. Participants attended ≥90% of dance sessions and did not experience loss of balance or fall. ADRD participants danced an average of 70 min per week. Both groups had improvements in agitation from baseline to 12 weeks., Conclusions: Twelve weeks of adapted dance was shown to be feasible and enjoyable for persons living with ADRD. Clinicians should consider adapted dance as part of an exercise prescription.

Importance: New pharmacotherapy options are needed for posttraumatic stress disorder (PTSD)., Objective: To investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD., Design, Setting, and Participants: This was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023. The study had a 1-week, placebo run-in period followed by an 11-week, double-blind, randomized, active-controlled, parallel-arm period (with 21-day follow-up) and took place at 86 clinical trial sites in the US. Adult outpatients with PTSD were enrolled (volunteer sample)., Interventions: Oral brexpiprazole 2 to 3 mg per day (flexible dose) + sertraline 150 mg per day or sertraline 150 mg per day + placebo (1:1 ratio) for 11 weeks., Main Outcomes and Measures: The primary end point was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score (which measures the severity of 20 PTSD symptoms) from randomization (week 1) to week 10 for brexpiprazole + sertraline vs sertraline + placebo. Safety assessments included adverse events., Results: A total of 1327 individuals were assessed for eligibility. After 878 screen failures, 416 participants (mean [SD] age, 37.4 [11.9] years; 310 female [74.5%]) were randomized. Completion rates were 137 of 214 participants (64.0%) for brexpiprazole + sertraline and 113 of 202 participants (55.9%) for sertraline + placebo. At week 10, brexpiprazole + sertraline demonstrated statistically significant greater improvement in CAPS-5 total score (mean [SD] at randomization, 38.4 [7.2]; LS mean [SE] change, -19.2 [1.2]; n = 148) than sertraline + placebo (randomization, 38.7 [7.8]; change, -13.6 [1.2]; n = 134), with LS mean difference, -5.59 (95% CI, -8.79 to -2.38; P < .001). All key secondary and other efficacy end points were also met. Treatment-emergent adverse events with incidence of 5% or greater for brexpiprazole + sertraline (and corresponding incidences for sertraline + placebo) were nausea (25 of 205 [12.2%] and 23 of 196 [11.7%]), fatigue (14 of 205 [6.8%] and 8 of 196 [4.1%]), weight increase (12 of 205 [5.9%] and 3 of 196 [1.5%]), and somnolence (11 of 205 [5.4%] and 5 of 196 [2.6%]). Discontinuation rates due to adverse events were 8 of 205 participants (3.9%) for brexpiprazole + sertraline and 20 of 196 participants (10.2%) for sertraline + placebo., Conclusions and Relevance: Results of this randomized clinical trial show that brexpiprazole + sertraline combination treatment statistically significantly improved PTSD symptoms vs sertraline + placebo, indicating its potential as a new efficacious treatment for PTSD. Brexpiprazole + sertraline was tolerated by most participants, with a safety profile consistent with that of brexpiprazole in approved indications., Trial Registration: ClinicalTrials.gov Identifier: NCT04124614.

Errors in multiple sequence alignments (MSAs) are known to bias many comparative evolutionary methods. In the context of natural selection analyses, specifically codon evolutionary models, excessive rates of false positives result. A characteristic signature of error-driven findings is unrealistically high estimates of dN/dS (e.g., >100), affecting only a small fraction (e.g., ~0.1%) of the alignment. Despite the widespread use of codon models to assess alignment quality, their potential for error correction remains unexplored. We present BUSTED-E: a novel method designed to detect positive selection while concurrently identifying alignment errors. This method is a straightforward adaptation of the BUSTED flexible branch-site random effects model used to fit distributions of dN/dS, with an important modification: it integrates an "error-sink" component representing an abiological evolutionary regime (dN/dS > 100), and provides the option for masking errors in the MSA for downstream analyses. Statistical performance of BUSTED-E on data simulated without errors shows that there is a small loss of power, which can be mitigated by model averaged inference. Using four published empirical datasets, we show BUSTED-E reduces unrealistic rates of positive selection detection, often by an order of magnitude, and improves biological interpretability of results. BUSTED-E also detects errors that are largely distinct from other popular alignment cleaning tools (HMMCleaner and BMGE). Overall, BUSTED-E is a robust and scalable solution for improving the accuracy of evolutionary analyses in the presence of residual alignment errors, contributing to a more nuanced understanding of natural selection and adaptive evolution.

Technologies for axon guidance for in vitro disease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350 nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designing in vitro platforms and in vivo neural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies.

State transitions are an acclimatory response by which plants, algae, and cyanobacteria counteract photosynthetic inefficiency caused by changes in incident light quality. In plants and green algae, state transition 7 (STN7/STT7) kinase promotes state 2 transition. Conserved cysteine residues are implicated in STN7/STT7 regulation, but the precise nature of their involvement remains unclear. Here, an analysis of the STN7 thiols in vitro and a determination of their midpoint redox potential indicate that the lumenal disulfide linkage is unlikely to be redox regulated while the stromal cysteines form a regulatory intramolecular disulfide. We further show that thioredoxin f1 (Trx-f1) reduces the STN7 stromal disulfide linkage as consistent with a Trx-f1-mediated inhibition of the kinase under high light., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Although opioid abuse is more prevalent in young individuals, opioid use, overdose, and use disorders continue to climb at a rapid rate among the elderly. Little is known about abuse potential in a healthy aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (mean: 19 weeks) and old (mean: 101 weeks), and were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also substantially greater in old mice compared to their young counterparts; however, we did not see increased intake of fentanyl with age at either dose tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but again this was not observed with fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.

Heated tobacco products (HTPs) are electronic devices that heat tobacco sticks to temperatures much lower than those which cause pyrolysis and combustion in cigarettes. While this electrical heating causes the formation of an inhalable aerosol which contains nicotine, the aerosol from HTPs contains significantly fewer and lower levels of the harmful and potentially harmful chemicals found in cigarette smoke. As a result, HTP use potentially conveys reduced risks to health compared to cigarette smoking. While this relative reduction in individual health risk is becoming clearer, what is less certain is the impact of HTPs on overall population‑level health, taking into account both the potential positive impact on adult smokers who completely switch to using HTPs and any unintended impacts such as use by tobacco non‑users and particularly by youth. The aim of this scoping review was to collate and evaluate the published scientific evidence to date, with a cut‑off of 1 January 2024, investigating the impact of HTPs on population‑level health. This evaluation suggests that HTP use is almost exclusively observed among those with a history of cigarette smoking, and there is a growing body of evidence for the ability of HTPs to provide support for adult smokers to transition away from cigarette smoking, in the absence of any significant "gateway" into tobacco use initiation. Many studies have reported a significant degree of dual use of cigarettes and HTPs, and efforts to assess the reasons for such patterns of use, whether these provide overall exposure reductions, and whether dual use acts as a bridge towards a complete transition away from cigarette smoking, requires further investigation. In addition, correction of the widespread and increasing misperceptions of HTPs among adult smokers is recommended to promote HTP uptake as a potentially less harmful alternative to smoking in this population., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This writing of this review was funded by Imperial Brands PLC, a manufacturer of tobacco and nicotine products including heated tobacco products. Financial relationships: Ian M. Fearon declare(s) personal fees from Imperial Brands PLC. Ian M. Fearon declare(s) personal fees from LA Clinical Trials, LLC. Ian M. Fearon declare(s) personal fees from Cheerain HK Ltd. Ian M. Fearon declare(s) personal fees and stock/stock options from British American Tobacco. Ian M. Fearon declare(s) personal fees from RAI Services Company. Ian M. Fearon declare(s) personal fees from Shenzhen Smoore Technology, Ltd. Ian M. Fearon declare(s) personal fees from Advanced Inhalation Rituals, Ltd. Ian M. Fearon is a Non-Executive Director with Advanced Inhalation Rituals, Ltd., a manufacturer of waterpipe tobacco and electronic waterpipe products. Ian M. Fearon declare(s) personal fees and stock/stock options from Qnovia, LLC. Ian M. Fearon is a consultant to, and Scientific Advisory Board Member of, Qnovia, LLC, an inhaled nicotine pharmaceutical smoking cessation product manufacturer. Thomas Nahde declare(s) employment and stock/stock options from Reemtsma Cigarettenfabriken GmbH. Employed by Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC company. Sarah F. Cordery, Martin Fitzpatrick, Sarah Weaver, Matthew Stevenson, Erika Grandolfo, and Layla Malt declare(s) employment and stock/stock options from Imperial Brands PLC. Ian M. Fearon declare(s) personal fees from Tobacco and nicotine product manufacturers and CROs. Ian M. Fearon is an independent consultant to tobacco and nicotine product manufacturers, and CROs, and provides scientific support for clinical and behavioural studies and general regulatory support. These manufacturers/CROs are unspecified for confidentiality reasons. Ian M. Fearon declare(s) employment from Broughton Life Sciences, Ltd. Ian M. Fearon declare(s) personal fees from E-Alternative Solutions, LLC. Ian M. Fearon declare(s) personal fees from Shenzhen JWEI Electronics Co., Ltd. Ian M. Fearon declare(s) personal fees from JUUL Labs and JUUL Labs UK Holdco, Ltd. Ian M. Fearon declare(s) employment from McKinney Regulatory Science Advisors, LLC. Ian M. Fearon declare(s) Travel expenses from Messe Dortmund GmbH. To attend and present at a tobacco expo. Keith Thompson declare(s) employment from Elucid8 Holdings Ltd. Employed by Elucid8 Holdings Ltd. and is acting as an independent scientific consultant to Imperial Brands PLC. Keith Thompson is a former employee of Gallaher Ltd. and Japan Tobacco International UK Ltd. Imperial Brands and Japan Tobacco International produce the electrically heated tobacco products ‘Pulze’ and ‘Ploom’, respectively. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fearon et al.)

In recent years, the concept of One Health (OH) has arisen as an approach that helps to catalyze the creation of transdisciplinary teams needed for surveillance and investigation of emerging disease dynamics. Besides a wealth of descriptions of what the OH approach encompasses, a dearth of information is available regarding the training of individuals in OH competencies. In 2019, the Nigerian Center for Disease Control developed an OH strategic plan to meet the country's human, animal, and environmental health challenges. In response to the demand for clinicians, scientists, climatologists, conservationists, and environmentalists, who have expertise in environment, human, plant, and animal health to work collaboratively in addressing OH challenges in Nigeria. An interprofessional group of faculty from the University of Texas Medical Branch, the University of Jos, and the National Veterinary Research Institute convened to develop a novel OH course 'entitled 'One Health for Translational Team Science. The objective of the course was to explore the evolution of an emerging epidemic, capitalizing on various learning environments, including animal, environmental, human, and public health perspectives. The 6-week course comprised of three parts: 2-weeks virtual part of case-based group discussions focusing on animal and environmental aspects, 2 weeks of individual field experiences, and a final virtual part focusing on human health. Pedagogical tools used were: case-based group discussions, breakout group presentations, role-play activities, field project write-up, peer evaluation, group writing assignments, and weekly reflections with the goal of working in teams to develop and practice the fundamental leadership and management skills in addressing emerging public health challenges. Post-course evaluations showed that all participants felt more confident identifying and practicing the necessary attitudes and skills to participate effectively in the evaluation of an outbreak. Furthermore, the roles, responsibilities, and "One Health ways of thinking" for the various disciplines and professions involved in improving global health were articulated and identified., Competing Interests: The 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 © 2024 Shehu, Luka, Bente, Weka, Weldon, Pam, Cadmus, Dami, Paessler, Weaver and Dacso.)

Introduction: Lassa fever is a zoonotic infectious disease endemic in West Africa with a high case-fatality rate and reported stigmatization of surviving patients. This study examines discrimination among survivors of Lassa fever (LF) complicated by hearing loss (HL)., Methods: This cross-sectional qualitative study used an in-depth interview guide to collect information from patients with HL about their experience of stigma. Interviews were conducted by a trained team of interviewers at the Jos University Teaching Hospital between January and April 2022 in Hausa language after informed consent was obtained. Recordings of the interviews were transcribed and translated from Hausa to English. Data analysis was conducted using NVivo software using a thematic framework approach., Results: Most (73%) respondents were male ( n  = 11); 27% were female ( n  = 4). The median age was 35 years (interquartile range, 16.5). Some Lassa fever patients experienced stigma and discrimination (53%) including isolation and withdrawal of family and community support during and after illness. HL increased stigma, as some patients were labeled "deaf" by other community members, increasing perceived stigma and devaluation. HL affected the socio-economic wellbeing of some who could not communicate well with their families and customers and constrained social interactions, evoking pain and apathy. Some survivors of LF and victims of its sequelae of HL experienced double stigmatization. While they were ill with LF, a third of respondents reported avoidance and isolation by family and community members who withdrew care and support both to them and their close family members. These forms of stigmatization strained their relationships., Conclusion: There is a need to address stigma in LF survivors who develop HL through concerted community-owned awareness to improve their quality of life along with a robust social support system to aid prevention., Competing Interests: The 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 © 2024 Best, Ameh, Weldon, Shwe, Maigari, Turaki, Ma’an, Yilgwan, Makishima, Weaver, Paessler and Shehu.)

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07&#95;BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials., Competing Interests: The 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 © 2024 Weaver, Dávila Conn, Ji, Verdonk, Ávila-Ríos, Leigh Brown, Wertheim and Kosakovsky Pond.)

Background/Objectives : Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods : This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results : We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions : Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

Play spaces are important components of paediatric healthcare environments. They provide children with critical opportunities to experience the social, emotional, and developmental benefits of play while in healthcare settings for appointments or hospitalizations. These spaces can help to mitigate stress, provide a sense of normalcy in unfamiliar environments, and facilitate social engagement for children and their families. Given the benefits of play spaces in paediatric healthcare settings, it is important to understand how these spaces can be designed to enhance children's inclusion and quality of care. The aim of this scoping review was to explore the current understanding of paediatric play space design. Using search terms related to children, health care, and play space, six interdisciplinary databases were searched over a 30-year period. The search found 2,533 records from which eighteen were included for review. Findings suggest that although it is well-documented that play spaces offer valuable social and emotional benefits, little is known about the specific design features that can and should be incorporated to enhance play opportunities and ensure that they benefit all children and families. Further, the literature mostly considers play spaces in the context of designated play or recreational rooms. Scholars are encouraged to consider how play opportunities can be incorporated into the designs of paediatric healthcare environments beyond the boundaries of these rooms. Future studies should also consider the diversity of play space users, including children of varying ages and abilities, to create more accessible and inclusive paediatric play spaces for children and their families. Advancing knowledge on play space design can help to optimize the quality of these important spaces and to ensure their designs meaningfully enhance children's play experiences and quality of care., Competing Interests: The 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., (© 2024 Yu, Weaver, Walker, Hess, Mac and Ross.)

Heated tobacco products represent a novel category of tobacco products in which a tobacco consumable is heated to a temperature that releases nicotine from the tobacco leaf but not to a temperature sufficient to cause combustion. Heated tobacco products may therefore have the potential to be a less harmful alternative for adult smokers who would otherwise continue to smoke cigarettes, as their use should result in exposure to substantially fewer and lower levels of toxicants. This update represents a two-year extension to our previous narrative review, which covered peer-reviewed journal articles published up to August 31, 2021. The scientific evidence published between 2021 and 2023 continues to indicate that aerosols produced from heated tobacco products contain fewer and substantially lower levels of harmful and potentially harmful constituents and that these observed reductions consistently translate to reduced biological effects in both in vitro and in vivo toxicological studies. Biomarker and clinical data from studies in which product use is controlled within a clinical setting continue to suggest changes in levels of biomarkers of exposure, biomarkers of potential harm, and clinical endpoints indicating the potential for reduced harm with switching to exclusive use of heated tobacco products in adult smokers. Overall, the available peer-reviewed scientific evidence continues to indicate that heated tobacco products offer promise as a potentially less harmful alternative to cigarettes, and as such, the conclusions of our original narrative review remain valid., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: SC, MS, LS, FC, EG, LM, and SW are employed by Imperial Brands Plc, UK. TN is employed by Reemtsma Cigarettenfabriken GmbH, an Imperial Brands Plc. company. KT is an employee of Elucid8 Holdings Ltd. and is acting as an independent scientific consultant to Imperial Brands Plc. KT is a former employee of Gallaher Ltd. and Japan Tobacco International UK Ltd. Imperial Brands and Japan Tobacco International produce the electrically heated tobacco products ‘Pulze’ and ‘Ploom’, respectively. IMF is an independent consultant to vaping/tobacco product manufacturers, including Imperial Brands Plc, to provide scientific and regulatory support. IMF is a Non-Executive Director with Advanced Inhalation Rituals Ltd, a manufacturer of waterpipe tobacco and electronic waterpipe products, and is also a retained Scientific Advisory Board member of Qnovia, LLC, an inhaled nicotine pharmaceutical smoking cessation product manufacturer. Financial relationships: Ian M. Fearon declare(s) personal fees, employment and stock/stock options from BAT. SC, EG, LM, LS, FC, MS, and SW declare employment and stock/stock options from Imperial Brands PLC. IMF declares personal fees from RAI Services Company. IMF declares personal fees from Shenzhen Smoore Technology Ltd. IMF declares personal fees from LA Clinical Trials, LLC. IMF declares personal fees, stock/stock options and Scientific Advisory Board member from Qnovia, Inc. IMF declares personal fees and stock/stock options from British American Tobacco. IMF declares personal fees from Imperial Brands PLC. TN declares employment and stock/stock options from Reemtsma Cigarettenfabriken. IMF declares personal fees from tobacco and nicotine product manufacturers and contract research organizations (CROs). IMF is an independent consultant to tobacco and nicotine product manufacturers and CROs and provides scientific support for clinical and behavioral studies and general regulatory support. These manufacturers/CROs are unspecified for confidentiality reasons. IMF declares employment with Broughton Life Sciences Ltd. IMF declares travel expenses to attend the tobacco expo from Messe Dortmund GmbH. IMF declares personal fees from E-Alternative Solutions, LLC. IMF declares personal fees from Shenzhen JWEI Electronics Co., Ltd. IMF declares personal fees from JUUL Labs and JUUL Labs UK Holdco Ltd. IMF declares personal fees from Cheerain HK Ltd. IMF declares personal fees from Advanced Inhalation Rituals Ltd. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cordery et al.)

Objectives: This study aims to assess exposure to e-cigarette advertising across multiple marketing channels among U.S. youth and to examine whether racial/ethnic disparities exist in exposure to e-cigarette advertisements., Study Design: This is a cross-sectional study., Methods: Cross-sectional data were drawn from a longitudinal survey of participants recruited from two nationally representative panels (NORC's AmeriSpeak® and GfK's KnowledgePanel). A total of 2043 youth aged 13-17 completed the initial 2018 survey, and 2013 youth completed the follow-up survey in 2019 (including a replenishment sample of 690 youth). Outcome variables were self-reported e-cigarette advertisement exposure in the past three months through various sources, such as television, point of sale, and online/social media. Generalized estimating equation models were used to estimate the adjusted odds ratios (AOR) of the association between racial/ethnic identity and e-cigarette advertisement exposure., Results: The prevalence of reported exposure to e-cigarette advertisements through any channel was 79.8% (95% CI: 77.1-82.2) in 2018 and 74.9% (95% CI: 72.5-77.1) in 2019, respectively. Point of sale was the most common source of e-cigarette advertisement exposure in both years. Non-Hispanic Black and non-Hispanic Asian youth were more likely to report exposure to e-cigarette advertisements through television (AOR = 2.07, 95% CI: 1.44-2.99 and AOR = 2.11, 95% CI: 1.17-3.82, respectively) and online/social media (AOR = 1.61; 95% CI: 1.11-2.33 and AOR = 1.99, 95% CI: 1.10-3.59, respectively) channels compared with non-Hispanic White youth., Conclusions: A substantial proportion of U.S. youth reported exposure to e-cigarette advertising through a variety of marketing channels. Significant racial/ethnic disparities existed, with non-Hispanic Black and Asian youth reporting more marketing exposure than their non-Hispanic White counterparts., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Implementation science researchers often cite clinical champions as critical to overcoming organizational resistance and other barriers to the implementation of evidence-based health services, yet relatively little is known about who champions are or how they effect change. To inform future efforts to identify and engage champions to support HPV vaccination, we sought to describe the key characteristics and strategies of vaccine champions working in adolescent primary care., Methods: In 2022, we conducted a national survey with a web-based panel of 2527 primary care professionals (PCPs) with a role in adolescent HPV vaccination (57% response rate). Our sample consisted of pediatricians (26%), family medicine physicians (22%), advanced practice providers (24%), and nursing staff (28%). Our survey assessed PCPs' experience with vaccine champions, defined as health care professionals "known for helping their colleagues improve vaccination rates.", Results: Overall, 85% of PCPs reported currently working with one or more vaccine champions. Among these 2144 PCPs, most identified the champion with whom they worked most closely as being a physician (40%) or nurse (40%). Almost all identified champions worked to improve vaccination rates for vaccines in general (45%) or HPV vaccine specifically (49%). PCPs commonly reported that champion implementation strategies included sharing information (79%), encouragement (62%), and vaccination data (59%) with colleagues, but less than half reported that champions led quality improvement projects (39%). Most PCPs perceived their closest champion as being moderately to extremely effective at improving vaccination rates (91%). PCPs who did versus did not work with champions more often recommended HPV vaccination at the earliest opportunity of ages 9-10 rather than later ages (44% vs. 33%, p < 0.001)., Conclusions: Findings of our national study suggest that vaccine champions are common in adolescent primary care, but only a minority lead quality improvement projects. Interventionists seeking to identify champions to improve HPV vaccination rates can expect to find them among both physicians and nurses, but should be prepared to offer support to more fully engage them in implementing interventions., (© 2024. The Author(s).)

Introduction: In cases of significantly displaced or comminuted mandible fractures, surgical guide splints can be developed to create the normal preinjury occlusion rather than placing patients in maxillomandibular fixation. Standard fracture fixation involves bending of plates intraoperatively based on surgeon-constructed dental splints which is prone to error., Methods: A 38-year-old male experienced a gunshot wound to the face that resulted in mandibular angle fractures bilaterally causing severely deranged occlusion and free-floating anterior mandible segment. Virtual surgical planning (VSP) software was used to recreate the injury-induced anatomy and anticipated postoperative anatomy. It also provided a surgical guide splint and a framework to preoperatively bend reconstruction plates to assist in achieving proper occlusion., Results: He underwent open reduction internal fixation of comminuted mandible fractures with lingual guide splint placement 10 days after injury. Following lingual splint application, the reconstruction plate was applied from angle to angle. The lingual splint was maintained for 3 weeks postoperatively to support the stabilization, and he was able to tolerate a regular diet and showed no evidence of wound breakdown., Discussion: Virtual surgical planning has had important implications in craniofacial surgery, orthognathic surgery, maxillomandibular reconstruction, and orbital reconstruction after tumor resection, temporomandibular joint surgery, and others. However, there have only been isolated reports describing the role of VSP in the facial trauma setting. In this technical study, the authors demonstrate the benefits of VSP and surgical guide splinting in trauma settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Tobacco harm reduction (THR) refers to strategies designed to reduce the health risks associated with tobacco smoking but may involve continued use of nicotine and/or tobacco. Next-generation products (NGPs) are a THR alternative as they do not burn tobacco or produce smoke and deliver nicotine and have fewer and substantially lower levels of harmful chemicals compared to cigarettes. Tobacco‑free nicotine pouches (TFNPs) are an emerging category of nicotine‑containing oral products that do not combust or contain tobacco leaf. Similar to Swedish snus, TFNPs are placed between a user's lip and gum, and nicotine is absorbed through the oral mucosa rather than being inhaled. The aim of this scoping review was to systematically collate and evaluate published scientific evidence (cut‑off of 31 May 2023) identified from bibliometric databases investigating the potential of TFNPs to contribute to THR. Overall, studies examining chemical constituents indicated that the use of TFNPs may result in lower exposure to toxicants than other tobacco or nicotine-containing products, both combustible and non‑combustible. This reduction in toxicant exposure has been demonstrated by multiple human biomarker studies and  in vitro  toxicological assessments to translate to harm reduction potential in smokers switching to TFNPs. However, further study is warranted. At present, there is some evidence from human behavioral research that TFNPs can support either transitioning away from smoking or reducing cigarette consumption. Furthermore, TFNP use appears very much limited to current users of traditional tobacco products, and youth uptake has been limited. In conclusion, the findings of this review indicate that TFNPs have the potential to support THR efforts and may help inform evidence‑based regulation., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Grandolfo et al.)

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.