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Midshipmen attending the U.S. Naval Academy (USNA) are required to awaken early, participate in athletic activities, and attend all academic classes and meals, which may limit opportunities for sleep as well as lead to increased stress. The purpose of this study was to examine the effects of a change to the standard daily schedule on self-reported sleep quality, sleep duration, and perceived stress in USNA midshipmen. Midshipmen completed the Pittsburgh Sleep Quality Index (PSQI) and Perceived Stress Scale (PSS) at two time points before (T1, T2) and following (T3, T4) a change to their standard daily schedule. The schedule change (1) extended the mid-day break from 105 to 115 minutes for all midshipmen and (2) shifted the standard "lights out" time for freshmen from 2300 to 2200. The earlier lights-out time was recommended for other classes (sophomore, junior, senior) of midshipmen, but only mandated for freshmen. Repeated measures ANOVA was used to examine group differences across time. Cohen's d was used to measure the magnitude of the schedule change effect on differences over time within a group. Two linear mixed models were estimated to examine the directional associations between stress and sleep quality across time. 733 participants (M: n&#x2009;=&#x2009;511; W: n&#x2009;=&#x2009;222) completed the questionnaires at T1, though the final sample sizes for those with complete data across all four timepoints for the PSQI and PSS were 359 and 410 midshipmen, respectively. Freshmen reported improved sleep quality from (1) T1 to T3 (6.9&#x2009;&#xb1;&#x2009;3.0 vs. 5.8&#x2009;&#xb1;&#x2009;2.7; P&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;0.27) and (2) T1 to T4 (6.9&#x2009;&#xb1;&#x2009;3.0 vs. 6.1&#x2009;&#xb1;&#x2009;3.0; P&#x2009;=&#x2009;.04, d&#x2009;=&#x2009;0.27). In contrast, juniors reported decreased sleep quality from (1) T1 to T3 (6.8&#x2009;&#xb1;&#x2009;3.1 vs. 7.7&#x2009;&#xb1;&#x2009;3.3; P&#x2009;=&#x2009;.013, d&#x2009;=&#x2009;0.20) and (2) T2 to T3 (6.7&#x2009;&#xb1;&#x2009;2.9 vs. 7.7&#x2009;&#xb1;&#x2009;3.3; P&#x2009;=&#x2009;.003, d&#x2009;=&#x2009;0.29). Freshmen reported increased hours of sleep duration from (1) T1 to T3 (6.4&#x2009;&#xb1;&#x2009;0.9 vs. 6.7&#x2009;&#xb1;&#x2009;0.7; P&#x2009;=&#x2009;.002, d&#x2009;=&#x2009;0.38), (2) T2 to T3 (6.2&#x2009;&#xb1;&#x2009;1.0 vs. 6.7&#x2009;&#xb1;&#x2009;0.7; P&#x2009;<&#x2009;.001, d&#x2009;=&#x2009;0.54), and (3) T2 to T4 (6.2&#x2009;&#xb1;&#x2009;1.0 vs. 6.6&#x2009;&#xb1;&#x2009;0.8; P&#x2009;<&#x2009;.001, d&#x2009;=&#x2009;0.38). In contrast, juniors reported decreased sleep duration from T1 to T4 (6.4&#x2009;&#xb1;&#x2009;0.9 vs. 6.1&#x2009;&#xb1;&#x2009;0.9; P&#x2009;=&#x2009;.021, d&#x2009;=&#x2009;0.31). Seniors reported increased perceived stress from T1 to T3 (11.9&#x2009;&#xb1;&#x2009;5.5 vs. 13.8&#x2009;&#xb1;&#x2009;6.5; P&#x2009;=&#x2009;.008, d&#x2009;=&#x2009;0.27). Lastly, a significant lagged perceived stress &#xd7; time interaction (P&#x2009;<&#x2009;.001) was found, suggesting that the effect of prior stress on sleep varied across time. These data suggest that a schedule change that included a mandated earlier "lights out" time resulted in improved sleep quality and duration among freshmen midshipmen, though the magnitudes of change were small. The extent to which this improvement contributes to increased academic performance and physical readiness warrants further attention.

Concerns persist within the surgical community that completion of an accredited surgical residency no longer consistently ensures that trainees are ready for independent practice. In response, the Independent Committee for Graduate Surgical Education (ICGSE) was established in January 2025 to address the unique requirements of surgical training. The committee's mandate was to recommend program standards that would potentially optimize education and training for surgical residents, with the goal of improving patient care. The ICGSE, consisting of 71 surgeons across 16 specialties, reviewed the history of surgical accreditation and relevant literature. Workgroup-led discussions identified strategies for improving trainee readiness and modernization of program accreditation standards. A literature review showed a "readiness gap" affecting 20%-30% of surgical trainees across multiple specialties. Key areas for improvement include:1. Designing curricula that increase clinical exposure, promote progressive autonomy, and facilitate transition to independent practice.2. Aligning training with the realities of surgical practice.3. Balancing accreditation requirements with efforts to reduce administrative burden and enhance faculty development.4. Emphasizing program evaluation beyond board passage rates and surveys to include real-time and longitudinal tracking of skill and clinical judgment acquisition.5. Supporting faculty education in teaching and assessment.6. Providing clear developmental roadmaps for lifelong learning. 1. Modernize accreditation through application of continuous quality improvement processes.2. Implement an outcomes-focused curriculum adaptable to each specialty that encourages innovation.3. Supplement case logs with an evidence-based framework for assuring procedural competency.4. Require standardized nontechnical skills training and assessment.5. Establish a longitudinal, competency-based assessment system.6. Mandate verifiable faculty development with institutional support. The ICGSE recommends that the graduate surgery education community, in collaboration with oversight organizations and professional associations, work to develop common surgery-focused accreditation standards that would drive the excellence required in surgical care.

Achieving sufficient vaccination coverage to mitigate disease outbreaks remains a persistent challenge in Nigeria, particularly for less-established vaccination programs. We aimed to obtain stakeholder recommendations for optimizing the implementation and uptake of less-established adult and childhood vaccination programs in Nigeria. We conducted eight Focus Group Discussions (FGDs) and 53 interviews with 132 participants purposively selected from three Nigerian states, Oyo, Nasarawa, and the Federal Capital Territory. Data were analyzed using inductive thematic analysis. Participants made several cross-cutting recommendations for optimizing less-established adult and childhood vaccination programs across five themes: 1. Institutional readiness as a foundational determinant of program performance; 2. Multilevel trust mechanisms operating through community engagement, co-creation, peer advocacy, and adverse event governance; 3. The emergency mobilization and routine institutionalization tension; 4. Policy enablers, including incentive schemes and vaccination mandates; and 5. Operational enablers, including risk communication and multisectoral coordination. Program-specific recommendations addressed reminder systems, schedule alignment, and integrated service delivery for measles second dose and malaria vaccination for children. This study generated recommendations for policymakers and program managers in Nigeria and similar contexts to improve vaccination implementation and uptake in both routine and outbreak settings.

As the Indian medical device ecosystem reaches a state of rigorous maturity, a significant friction point has emerged between corporate governance and regulatory oversight. Currently, when an established importer, an entity with an unblemished history of compliance, undergoes a routine constitutional change (such as a transition from a private limited to a limited company), the regulator often mandates a "fresh license" application. This administrative requirement effectively ignores the entity's entire history of post-market surveillance (PMS) and safety compliance, treating a seasoned market participant as a brand-new entrant. This article examines the "importer paradox" and argues that the logic of the Central Drugs Standard Control Organisation's (CDSCO) "Subsequent Importer Scheme" (SIS) provides a compelling blueprint for reform. We propose a shift in regulatory philosophy: prioritizing the "Safety Anchor" of the medical device, which is tethered to its technical file and manufacturing site, over the "Legal Wrapper" of the corporate entity. By adopting a streamlined three-step transition involving a formal declaration of continuity, integration through the SIS portal, and a targeted administrative audit, the regulator can eliminate redundant filings. This approach would not only reduce the administrative burden on both the reviewer and the manufacturer but also ensure a more transparent and secure supply chain for Indian patients. Ultimately, regulatory science must recognize that corporate evolution should not be a trigger for technical re-evaluation when the underlying product safety remains unchanged.

National opioid settlements were intended to fund public health remediation, yet early evidence suggests significant institutional capture. In this study I analyze how differing state governance models across 13 Appalachian states shaped resource allocation during the initial disbursement phase. I conducted systematic document analysis of publicly available settlement expenditure records across 13 states in the Appalachia Opioid Remediation Database through July 2025, supplemented by investigative reporting and state transparency portals. I manually coded local, cash-in-hand expenditures into clinical remediation and non-clinical spending categories and calculated weighted capture rates across restrictive and permissive spending frameworks. The regional weighted mean capture rate for non-clinical law enforcement and administrative purposes was 8.4% ($10.2 million) of documented expenditures. Substantial variation existed across governance models: West Virginia's permissive framework produced a 41.2% verified capture floor, while North Carolina's restrictive model limited non-clinical allocation to 2.6%. Discrepancies in state-level oversight have produced significant resource allocation into law enforcement hardware and legacy municipal debts. Permissive spending frameworks appear structurally susceptible to fiscal supplantation. To defend future disbursements, standardized non-supplantation mandates and outcome-based auditing are recommended to prioritize clinical remediation over general infrastructure expansion.

Adolescence is a pivotal life stage during which individuals develop health-related attitudes and behaviours that frequently persist into adulthood, making it a crucial period for shaping long-term engagement with preventive care. Despite Italy's national recommendations for adolescent vaccines (HPV, MenACWY, and the dTap-IPV booster), coverage gaps persist. By analyzing the self-reported vaccination history of university students, this study aims to assess adolescent vaccine adherence, willingness to vaccinate and their predictors to better inform targeted public health interventions. A cross-sectional survey was conducted among university students (aged 18-29 years). An online, anonymous, self-administered questionnaire was developed to gather data on socio-demographic characteristics, past adherence to vaccinations offered during adolescence (i.e., HPV and MenACWY vaccines and the dTap-IPV booster), willingness to get vaccinated, factors influencing vaccination decision making, and sources of information on vaccinations. Among the 527 enrolled participants, 29% reported having received the MenACWY vaccine during adolescence, with the lack of healthcare worker (HCW) recommendation cited as the leading barrier (59.4%). HPV vaccine uptake was the strongest predictor of being vaccinated against MenACWY vaccination. A majority of the students (68.3%) reported receiving the HPV vaccine during adolescence, primarily to prevent HPV-related cancers (55.8%). Female sex, younger age, and higher parental education were positively associated with the HPV vaccine uptake. Additionally, 89.4% received the dTap-IPV booster, and this uptake was positively associated with both HPV and MenACWY vaccination. Notably, one-third (31.1%) reported that an HCW had discouraged vaccination, and even though nearly all (99.4%) cited HCWs as their primary source of information on vaccination. A persistent gap in adolescent vaccination adherence remains, particularly for MenACWY and HPV, driven by unbalanced risk perceptions and frequent missed clinical opportunities by HCWs. Conversely, vaccine mandates ensured high dTap-IPV coverage. The strong correlation across vaccine types highlights the potential of "clustered" immunization behaviors. To bridge these coverage gaps, interventions must strengthen HCW counseling, utilize low-friction delivery models like school-based clinics, and deploy dual-targeted strategies that reframe vaccination as a shared social responsibility.

In this research, we examine the determinants of citizens' beliefs about the severity of criminal and administrative sanctions attached to violations of COVID-19 mitigation laws in Russia, as well as extrajudicial sanctions employed in other parts of the world. Although criminological research has identified many predictors of punitive attitudes toward traditional criminal offenses, less is known about how citizens evaluate punishments for violations of newly introduced rules adopted under emergency conditions. The key explanatory variables in our study include beliefs in attribution of human behavior, self-commitment to compliance with COVID-19 mandates, trust in government, and the fear of COVID-19 infection. Data for the study come from 508 respondents from St. Petersburg, Russia's second-largest city, who participated in an online survey during the first wave of the pandemic in May 2020. Findings suggest that citizens who believe in the free-will explanations of human nature and those who are more likely to comply with pandemic-mitigating laws feel that the punishments imposed for violating the pandemic-related laws were not severe enough. Additionally, those who trust the government's effectiveness and integrity in controlling COVID-19 are more punitive, a finding contrary to crime-related punitiveness research. Together, these findings indicate that support for sanctioning pandemic-related violations is closely tied to rule-related evaluations, including responsibility attribution, institutional trust, and personal commitment to compliance. The study contributes to criminological research by showing that established explanations of punitive attitudes may operate differently when applied to newly institutionalized crisis rules. How People Judge Punishments for Breaking Emergency RulesThis study looks at how people decide whether punishments for breaking COVID-19 rules are too harsh or not harsh enough. We focus on people in Russia and examine both formal punishments, such as fines or legal penalties, and informal responses seen in other countries. Past research has identified many factors that shape opinions about punishment for traditional crimes, however, we know less about how people judge punishments for new rules introduced during emergencies like the pandemic. In this study, we focus on several key factors: whether people believe individuals are responsible for their actions, how willing they are to follow COVID-19 rules themselves, how much they trust the government, and how worried they are about getting infected. The study is based on an online survey of 508 people in St. Petersburg, conducted during the first wave of the pandemic in May 2020. The findings show that people who believe individuals have control over their actions, and those who are more willing to follow COVID-19 rules themselves, are more likely to think that punishments were not strict enough. We also find that people who trust the government to manage the pandemic tend to support stronger punishments. This is different from what we usually see in studies of crime, where higher trust in government is often linked to less support for harsh punishment. Overall, the results suggest that support for punishing pandemic-related rule-breaking is closely tied to how people think about responsibility, their trust in institutions, and their own commitment to following the rules. The study shows that ideas we use to explain attitudes toward punishment may work differently when applied to new rules created during a crisis.

Whole body computed tomography (WBCT) is widely used in the initial assessment of pediatric trauma patients to rapidly identify injuries; however, its routine use exposes children to substantial ionizing radiation. Clear guidance on which pediatric trauma patients truly benefit from WBCT is lacking, leading to practice variability and potential overuse in emergency departments. The proposed score is intended to complement existing pediatric imaging decision frameworks that emphasize selective and risk-based use of computed tomography. This retrospective, single-center observational study included trauma patients under 18 years of age who underwent WBCT in a tertiary pediatric trauma center between June 2021 and June 2022. The primary outcome was the presence of traumatic injuries involving&#x2009;&#x2265;&#x2009;2 anatomical regions on WBCT not necessarily the clinical need for WBCT. Candidate predictors were identified from the literature and clinical practice and evaluated using multivariable logistic regression. Continuous variables were dichotomized based on receiver operating characteristics (ROC) analysis. Independent predictors were used to develop a clinical decision support tool, the WHOLE score. Model performance was assessed using ROC analysis and diagnostic accuracy metrics. A total of 407 pediatric trauma patients who underwent WBCT were included; 37.6% (n&#x2009;=&#x2009;153), had injuries involving two or more anatomical regions. Independent predictors of multi-region injury were age&#x2009;&#x2265;&#x2009;133 months, tachycardia, hypoxia, positive physical examination findings in the head, thoracic, pelvic, or lower extremity regions, and aspartate aminotransferase (AST)&#x2009;&#x2265;&#x2009;50 U/L. These variables were incorporated into the WHOLE score (range 0-8). The WHOLE score demonstrated good discrimination (AUC 0.84; 95% CI 0.80-0.88). Using a cut-off of &#x2265;&#x2009;2 points, sensitivity was 96.7% (CI 92.5-98.9) and NPV was 94.8% for detecting multi-region injuries. The WHOLE score is a simple clinical decision support tool designed to identify pediatric trauma patients at low risk for multi-region injuries, thereby supporting emergency physicians in safely withholding WBCT in appropriately selected cases. The score functions as a rule-out tool: a low score (0-1) may support a decision to forego WBCT, whereas a high score does not independently mandate it. By reducing unnecessary WBCT in low-risk patients, the score has the potential to decrease radiation exposure while maintaining diagnostic safety. This is a preliminary single-center derivation study, and external prospective validation is required before routine clinical implementation. The study protocol was registered retrospectively at clinicaltrials.gov (Clinical Trials Identifier: NCT07411235, Date:11/02/2026).

There are studies on parent, patient and child preferences regarding hospital staff attire, but no corresponding studies on staff preferences. The COVID-19 pandemic in Australia coincided with a rapid change to scrubs as standard staff attire on hospital wards. These are often at staff choice, whereas theatre scrubs are typically mandated and supplied by the hospital. There is therefore choice outside theatre, but no choice for theatre staff. Survey staff preferences regarding two styles and colours of hospital-provided scrubs, along with reasons underpinning staff preferences. Anonymous survey of all in-theatre staff in response to a recent change in scrub uniforms. Mixture of survey and free-text responses to questions. A total of 267 staff responded, with the majority completing the survey. There were ~20&#x2009;000 words of free-text responses to analyse. There was a clear choice for dark colour, elastic waistband and trouser-style pockets over the alternative. Reasons fell into seven major categories: Comfort/fit/availability, professionalism, functionality/practicality, dignity/self-esteem, modesty/privacy, stains/sweat/dirt and safety. There was no clear preference for own scrubs vs. supplied scrubs, or for multiple options vs. everyone looking the same. Female staff particularly did not like lighter scrubs, with their risk of strikethrough menstrual bleeding. Staff have clear reasons for scrub preferences. Poorly designed scrubs present a hazard to physical safety and well-being. Light colours show stains, sweat and blood more. Underwear can be visible through poorly designed or light-coloured scrubs. There is a pride which comes from wearing well-fitting and functional theatre attire.

The Veterans Health Administration (VHA) Life-Sustaining Treatment Decisions Initiative (LSTDI) aims to improve documentation of patient preferences for life-sustaining treatment (LST), particularly in high-risk populations such as those served by Home Based Primary Care (HBPC) programs. Despite this mandate, LST documentation in HBPC remains variable. Previous studies suggest audit and feedback may be insufficient when used alone. This study evaluated whether combining audit and feedback with tailored implementation facilitation can increase and sustain LST documentation rates in HBPC. We evaluated the prospective implementation of a longitudinal intervention using retrospective data design with data from the VA Corporate Data Warehouse and HBPC Masterfile between October 2019 and December 2024. Eleven HBPC programs with historically low (<&#x2009;50%) LST documentation rates participated in a phased intervention consisting of a 6-month pre-implementation phase, a 15-month implementation phase, and a 12-month sustainability phase. The intervention combined monthly audit and feedback reports with site-specific implementation facilitation. We used a difference-in-differences (DID) analysis to compare changes in monthly site-level LST documentation rates at intervention sites (Cohorts 1-3) versus non-intervention sites (Cohort 4). The primary site-level outcome was the percentage of Veterans with a completed LST template. The analysis included a total of 140 VA sites, with 11 intervention sites across six VA regions. Intervention sites demonstrated a significant and sustained increase in LST documentation during implementation. The overall average treatment effect was 0.21 (95% CI: 0.144-0.276), corresponding to an average increase over expected trends of 21 percentage points across all intervention cohorts. This effect was maintained throughout the 12-month sustainability period across all cohorts. Pairing audit and feedback with implementation facilitation produced a substantial and durable improvement in LST documentation in HBPC settings. These findings support the use of these two complementary, data-driven implementation strategies to achieve policy goals of goal-concordant care for seriously ill Veterans.

Breast implants are a fundamental adjunct in aesthetic and reconstructive breast surgery, with more than 3.5 million recipients in the United States. Implant rupture risk increases with device age, although modern cohesive silicone implants demonstrate markedly improved durability. The Food and Drug Administration does not mandate routine replacement, but recommends surveillance screening for silicone implant rupture beginning 5-6 years postplacement and every 2-3 years thereafter. However, no guidelines exist for managing asymptomatic ruptures in older adult patients. A scoping review was conducted in MEDLINE, Embase, and the Cochrane Library through January 2025 for guidelines on the management of asymptomatic implant rupture in older adult patients; none was identified. Evidence indicates that although surveillance can detect silent ruptures and minimize silicone migration, the clinical impact in older adult patients is limited given the low incidence of symptomatic complications with modern devices and reduced life expectancy. Risks of surveillance include false positives, overdiagnosis, patient anxiety, and unnecessary surgery-particularly relevant in older patients with higher perioperative complication rates. The authors propose discontinuing surveillance for asymptomatic silicone implants after age 75 years and foregoing routine implant exchange. In asymptomatic patients older than 75 with known or suspected rupture, observation is reasonable unless symptoms develop. Symptomatic cases should undergo diagnostic imaging and individualized risk-benefit discussion using a comprehensive geriatric assessment framework. A shared decision-making approach is emphasized, balancing surgical risks, patient comfort with uncertainty, and aesthetic concerns. These recommendations aim to optimize quality of life and avoid overtreatment in older adult patients with breast implants.

Early identification of patients with acute pulmonary embolism (PE) who can be safely managed in the outpatient setting has become a central priority in contemporary clinical practice. While haemodynamic instability mandates urgent reperfusion, most patients are hemodynamically stable at admission and therefore require refined risk stratification to guide therapeutic decisions and determine the appropriate level of care. The 2019 European Society of Cardiology guidelines emphasise the importance of identifying low-risk patients who may be eligible for early discharge (within 24-48 h) and home-based anticoagulation. Over the past decade, substantial progress has been made in validating clinical, biochemical, and haemodynamic criteria capable of reliably stratifying low-risk patients. The introduction of direct oral anticoagulants further simplified anticoagulation pathways, enabling shorter hospital stays and safer outpatient management. Nevertheless, the implementation of early discharge and outpatient treatment strategies remains highly heterogeneous across countries, reflecting variations in national recommendations, healthcare system organisation, and resource availability. This review aims to synthesise the current evidence on outpatient management of acute PE, with a focus on risk-stratification strategies, cost-effectiveness considerations, and contemporary guideline recommendations.

BackgroundSurvival extrapolation is crucial in estimating the lifetime survival benefit of a treatment for health technology assessment (HTA). Conventional extrapolation methods, which assume that the long-term treatment effect (hazard ratio between treatment and comparator) follows the same pattern as observed in the short-term trial, have been challenged by a wide range of immuno-oncology therapies, particularly those with administrative stopping rules that mandate treatment discontinuation at a prespecified time point. A gradual waning of their treatment effects has been considered plausible and received growing attention from HTA stakeholders over the past decade. However, existing statistical methods often rely on unnecessarily strong waning assumptions.ObjectiveWe demonstrate the blended hazard method as a flexible way to account for treatment effect waning while incorporating external evidence in survival extrapolation.MethodThe blended hazard method fits separate parametric survival regression models to the observed randomized controlled trial data and external data that inform the common long-term hazard when there is no treatment effect. For each arm, the fitted internal and external hazard functions are blended based on a time-varying weight function, so that the blended hazard is initially dominated by the fitted internal hazard, then gradually approaches the fitted external hazard over a blending interval, and is finally dominated by the fitted external hazard. The time and rate of blending the internal and external information can be controlled by the weight function to allow for sensitivity analyses. NICE TA366 on pembrolizumab for advanced melanoma not previously treated with ipilimumab is used as a case study to demonstrate the practical implementation of this method.ResultsExtrapolations and restricted mean survival times from the blended hazard method closely matched the updated 7-y trial follow-up and showed better consistency than the TA366 base case across all sensitivity analysis scenarios.ConclusionThe method explicitly accounts for gradual treatment effect waning while incorporating external evidence and offers the flexibility to accommodate a broad range of waning scenarios, thereby effectively characterising uncertainty in extrapolation.HighlightsTreatment effect waning is considered plausible in survival extrapolation for many therapies, particularly those with treatment-stopping rules. However, there is a shortage of appropriate methods to model this phenomenon, and existing approaches either rely on strong waning assumptions or address it only as a post hoc check.We demonstrate the blended hazard method as a possible approach to account for treatment effect waning while incorporating external evidence.The blended hazard method possesses the flexibility to accommodate a wide range of waning scenarios, thereby relaxing unnecessarily strong assumptions and effectively characterizing uncertainty in survival extrapolation.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that can cause irreversible organ dysfunction and life-threatening complications. Although glucocorticoids are the standard first-line therapy, frequent flares necessitate prolonged use, which is in turn associated with toxicity. Inebilizumab, a CD19-targeted antibody approved in Japan in November 2025, demonstrated efficacy in the phase&#xa0;3 MITIGATE trial. However, the trial's eligibility criteria and controlled environment may not reflect the heterogeneity of the routine clinical setting or the long-term profile in the Japanese population. This study (4SigHT Study) aims to evaluate the long-term effectiveness and safety of inebilizumab in Japan. This multicenter, prospective, observational study plans to enroll 100 patients with definite or probable IgG4-RD who are initiating inebilizumab at up to 40 sites in Japan. The study runs from March 1, 2026 to March 31, 2032. It includes up to 14 scheduled visits over a maximum duration of 312&#xa0;weeks and reflects real-world decisions without mandated interventions. Comprehensive baseline assessments capture disease characteristics, comorbidities, vaccination history, and clinical history, including the frequency and nature of flares over the preceding 52&#xa0;weeks. Longitudinal data are collected via an electronic data capture system. To ensure data robustness, the study employs a rigorous adjudication process. Suspected flares treated by investigators are adjudicated by an independent data and safety monitoring board using standardized organ-specific flare criteria. The primary outcome is the proportion of participants with an adjudicated clinical flare through week&#xa0;52. Secondary outcomes include treatment-free complete remission, glucocorticoid-free complete remission, time to clinical flare, annual clinical flare rate, proportion of patients who initiate additional treatment, time to treatment initiation for new or worsening symptoms, and cumulative glucocorticoid dose. Furthermore, the study evaluates the long-term safety of inebilizumab over 6&#xa0;years. The study is registered with the Japan Registry of Clinical Trials (jRCT1031250749).

Helicopter emergency medical services (HEMS) and search and rescue operations represent the intersection of aviation complexity and clinical criticality. Despite technological advances in simulation, most training programs remain fragmented across aviation and medical domains, failing to integrate the human factors that determine mission success. This program report describes the longitudinal development of an integrated HEMS simulation training system, from early low-fidelity cabin prototypes to contemporary multi-sensory and hybrid simulation environments, and proposes a systems architecture framework applicable to next-generation air medical crew training. We describe the staged development of a longitudinal HEMS simulation training initiative in multiple years, evaluate relevant regulatory and competency-based training frameworks, review international centers of excellence, and synthesize lessons learned into an architectural proposal for integrated air medical training systems. Early multi-sensory simulation incorporating cabin noise, smoke, temperature changes, and communication systems demonstrated that clinical performance degrades significantly under operational stress-a finding now validated by evidence-based training frameworks. The September 2024 European Union Aviation Safety Agency regulatory update removing Full Flight Simulator mandates for helicopters, combined with virtual and mixed reality qualification milestones, creates unprecedented opportunity for hybrid training architectures. HEMS training requires systems thinking-not isolated course development. Organizations designing next-generation programs need professionals who can integrate competency frameworks, immersive technologies, behavioral assessment tools, and clinical-operational training into unified ecosystems. This report provides an architectural blueprint applicable to HEMS, search and rescue, and critical care transport.

Microbial network inference is an essential approach for revealing complex interactions within microbial communities. However, the lack of experimentally validated gold standards presents a significant obstacle in evaluating the biological accuracy of inferred networks. This study delivers a comprehensive comparative assessment of six widely used microbial network inference algorithms on four diverse real-world microbiome datasets alongside computationally generated samples, including synthetic, noisy, and bootstrap-derived variants. Our evaluation framework extends beyond conventional synthetic benchmarking by emphasizing reproducibility-focused assessments grounded in biologically realistic perturbations. Our analysis reveals that bootstrap resampling and low-level noisy datasets (&#x2264;10% perturbation) effectively preserve the key statistical properties of real microbiome data, serving as reliable proxies for assessing algorithmic consistency. Conversely, synthetic datasets generated via the widely used SPIEC-EASI method exhibit substantial divergence from real data. Notably, several algorithms fail to distinguish between structured and random networks, highlighting a lack of structural sensitivity and the limitations of overreliance on synthetic benchmarks. This study provides critical insights for the microbiome research community, emphasizing the need for more reliable and broadly applicable approaches to network evaluation. We propose a benchmarking framework that prioritizes real-data-derived perturbations and mandates rigorous statistical validation of synthetic datasets. Our findings highlight the importance of robustness and reproducibility analyses as complementary evaluation criteria for microbial network inference methods when validated biological ground truth is unavailable.