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This paper continues the discussion of three values of sport (safety, fairness, inclusion) that has developed around the theme of inclusion of transwomen in the female category in World Rugby, as discussed by Pike, Burke and Imbrišević. In contrast to their discussion, in which these three values have been seen from the limited perspective of the inclusion of one group of athletes into a specific category of one sport, they are here discussed in the context of the categorization in sport in general, with a focus on constitutive and eligibility rules. Constitutive rules give a strong foundation for eligibility rules. From the perspective of eligibility rules, the value of inclusion is identified as the underlying main value, while fairness and safety are its functions. This view rehabilitates the value of inclusion and has implications for how we think about the inclusion of athletes in sport, and for the creation of categories. [ABSTRACT FROM AUTHOR]

Keywords: Broken Arrows; nuclear weapons; accidents; safety; command and control; close call EN Broken Arrows nuclear weapons accidents safety command and control close call 148 154 7 05/16/23 20230501 NES 230501 In the world of accidents, close calls, and near-misses, perhaps nothing is more chilling than incidents involving nuclear weapons. So, to answer your question, the US Defense Department uses "Broken Arrow" to mean a nuclear accident with a US weapon that caused the unauthorized launch or jettisoning of a nuclear weapon, a fire, an explosion, a radioactive release, or a full-scale detonation. More important, the large number of close calls and near-misses shows that no system for safeguarding nuclear weapons can ever be 100-percent effective - meaning that the United States (and other nuclear weapons nations, which have Broken Arrows of their own) can never completely eliminate the potential for catastrophic nuclear error. B Schlosser: b Right, we're not talking about close calls or near-misses with Russian weapons, British weapons, French weapons, or what might have happened with weapons in India, Pakistan, North Korea, China... Worldwide, we have no idea how many nuclear-weapon accidents have occurred. [Extracted from the article]

Summary: Xylem conduits have lignified walls to resist crushing pressures. The thicker the double‐wall (T) relative to its diameter (D), the greater the implosion safety. Having safer conduits may incur higher costs and reduced flow, while having less resistant xylem may lead to catastrophic collapse under drought. Although recent studies have shown that conduit implosion commonly occurs in leaves, little is known about how leaf xylem scales T vs D to trade off safety, flow efficiency, mechanical support, and cost.We measured T and D in > 7000 conduits of 122 species to investigate how T vs D scaling varies across clades, habitats, growth forms, leaf, and vein sizes.As conduits become wider, their double‐cell walls become proportionally thinner, resulting in a negative allometry between T and D. That is, narrower conduits, which are usually subjected to more negative pressures, are proportionally safer than wider ones. Higher implosion safety (i.e. higher T/D ratios) was found in asterids, arid habitats, shrubs, small leaves, and minor veins.Despite the strong allometry, implosion safety does not clearly trade off with other measured leaf functions, suggesting that implosion safety at whole‐leaf level cannot be easily predicted solely by individual conduits' anatomy. [ABSTRACT FROM AUTHOR]

• Higher doses of Ad26.COV2.S tended to be more immunogenic and more reactogenic than lower doses. • VNAs and S-bAbs persisted for at least 6 months after just 1 dose of Ad26.COV2.S 5 × 1010 vp. • Immune responses increased when the time interval between dose 1 and dose 2 increased. • Rapid, marked responses in all groups after vaccine antigen exposure indicate immune memory. • Durable immune responses were observed in all groups up to at least 6 months post vaccine antigen exposure. A single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored. This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18–55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 1010, 2.5 × 1010, 5 × 1010, and 1 × 1011 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 1010 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants. All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 1010 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related. The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 1010 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination. [ABSTRACT FROM AUTHOR]

Background: Bennett fractures are traditionally fixed with percutaneous K-wires from dorsal to volar, or with a volar to dorsal screw via a volar open approach. While volar to dorsal screw fixation is biomechanically advantageous, an open approach requires extensive soft tissue dissection, thus increasing morbidity. This study aims to investigate the practicality and safety of Bennett fracture fixation using a percutaneous, volar to dorsal screw, particularly with regard to the median nerve and its motor branch during wire and screw insertion. Methods: Fifteen fresh frozen forearm and hand specimens were obtained from the University of Auckland human cadaver laboratory. A guidewire is placed under image intensifier from volar to dorsal with the thumb held in traction, abduction and pronation. The wire is passed through the skin volarly under image intensifier, then the median nerve is dissected from the carpal tunnel and the motor branch of the median nerve (MBMN) is dissected from its origin to where it supplies the thenar musculature. The distance between the K-wire to the MBMN is measured. Results: In 14 of 15 specimens, the wire was superficial and radial to the carpal tunnel. The mean distance to the origin of the MBMN is 6.2 mm (95% CI 4.1–8.3) with the closest specimen 1 mm away. The mean closest distance the wire gets to any part of the MBMN is 3.7 mm (95% CI 1.6–5.8); in two specimens, the wire was through the MBMN. Conclusions: Wire placement, although done under image intensifier, is subject to significant variation in exiting location. While research has shown the thenar portal in arthroscopic thumb surgery is safe, our guidewire needs to exit further ulnar to capture the Bennett fracture fragment, placing the MBMN at risk. This cadaveric study has demonstrated the proposed technique is unsafe for use. [ABSTRACT FROM AUTHOR]

To determine the safety, feasibility, and potential effect of an 18-week exercise intervention for adults with primary brain cancer. Eligible patients were 12-26-weeks post-radiotherapy for brain cancer. The individually-prescribed weekly exercise was ≥150-minutes of moderate-intensity exercise, including two resistance-training sessions. The intervention was deemed "safe" if exercise-related, serious adverse events (SAE) were experienced by <10% of participants, and feasible if recruitment, retention, and adherence rates were ≥75%, and ≥75% compliance rates were achieved in ≥75% of weeks. Patient-reported and objectively-measured outcomes were assessed at baseline, mid-intervention, end-intervention, and 6-month follow-up, using generalized estimating equations. Twelve participants enrolled (51 ± 19.5 years, 5 females). There were no exercise-related SAEs. The intervention was feasible (recruitment:80%, retention:92%, adherence:83%). Participants completed a median of 172.8 (min:77.5, max:560.8) minutes of physical activity per week. 17% met the compliance outcome threshold for ≥75% of the intervention. Improvements in quality of life (mean change (95% CI): 7.9 units (1.9, 13.8)), functional well-being (4.3 units (1.4, 7.2)), depression (−2.0 units (−3.8, −0.2)), activity (112.8 min (42.1, 183.4)), fitness (56.4 meters (20.4, 92.5)), balance (4.9 s (0.9, 9.0)), and lower-body strength (15.2 kg (9.3, 21.1)) were observed end-intervention. Preliminary evidence support that exercise is safe and beneficial to the quality of life and functional outcomes for people with brain cancer.Registration: ACTRN12617001577303 The BRAin Cancer and Exercise (BRACE) study highlights the need for regular monitoring of disease- and treatment-related side effects which may present as barriers to exercise. Exercise prescription should be modified according to the presence and severity of disease- and treatment-related barriers. Adverse events observed, such as dizziness, highlight the importance of supervised exercise for people with brain cancer. If supervision is not possible, then exercise modes with low risk of harm from falls are recommended (e.g., walking, machine-based resistance training). [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the efficacy and safety of snare traction-assisted endoscopic submucosal dissection (ESD) for the management of circumferential superficial esophageal cancer. Methods: A total of 68 patients who underwent ESD for circumferential superficial esophageal cancer were included in this study. All the patients were divided into two groups based on whether the snare traction was used or not; the snare traction group (S-ESD, group n = 35) and the control group (C-ESD, group n = 33). Results: There was no significant difference in the size of the resected area between the groups [21.98 (18.30, 27.00) cm2 vs 24.00 (15.28, 30.72) cm2, P = 0.976]. The snare traction group had a shorter dissection time [92.00 (74.00, 121.00) min vs 110.00 (92.50, 137.00) min, P = 0.017] and a faster resection speed [0.28 ± 0.13 cm2/min vs 0.22 ± 0.11cm2/min, P = 0.040] compared to the control group. There were no statistically significant differences between the two groups in terms of hospital stay, cost, en bloc resection rate, R0 resection rate, curative resection rate, bleeding rate, perforation rate, stricture rate, and recurrence rate (P > 0.05). Conclusion: Snare traction-assisted ESD is a safe and efficient approach for the treatment of circumferential superficial esophageal cancer. Its advantages includes shorter procedure so the anesthesia requirement, clear operative filed view, improved mucosal dissection efficiency, simple, and easily accessible equipment. [ABSTRACT FROM AUTHOR]

Background: Application of artificial intelligence (AI) in general surgery is evolving. Real-world implementation of an AI-based computer-vision model in laparoscopic appendectomy (LA) is presented. We aimed to evaluate (1) its accuracy in complexity grading and safety adherence, (2) clinical correlation to outcomes. Methods: A retrospective single-center study of 499 consecutive LA videos, captured and analyzed by 'Surgical Intelligence Platform,' Theator Inc. (9/2020–5/2022). Two expert surgeons viewed all videos and manually graded complexity and safety adherence. Automated annotations were compared to surgeons' assessments. Inter-surgeons' agreements were measured. Since 7/2021 videos were linked to patients' admission numbers. Data retrieval from medical records was performed (n = 365). Outcomes were compared between high and low complexity grades. Results: Low and high complexity grades comprised 74.8 and 25.2% of 499 videos. Surgeons' agreements were high (76.9–94.4%, kappa 0.77/0.91; p < 0.001) for all annotated complexity grades. Surgeons' agreements were also high (96.0–99.8%, kappa 0.78/0.87; p < 0.001) for full safety adherence, whereas agreement was moderate in partial safety adherence and none (32.8–58.8%). Inter-surgeons' agreements were high for complexity grading (kappa 0.86, p < 0.001) and safety adherence (kappa 0.88, p < 0.001). Comparing high to low grade complexity, preoperative clinical features were similar, except larger appendix diameter on imaging (13.4 ± 4.4 vs. 10.5 ± 3.0 mm, p < 0.001). Intraoperative outcomes were significantly higher (p < 0.001), including time to achieve critical view of safety (29.6, IQR 19.1–41.6 vs. 13.7, IQR 8.5–21.1 min), operative duration (45.3, IQR 37.7–65.2 vs. 25.0, IQR 18.3–32.7 min), and intraoperative events (39.4% vs. 5.9%). Postoperative outcomes (7.4% vs. 9.2%) including surgical complications, mortality, and readmissions were comparable (p = 0.6), except length of stay (4, IQR 2–5.5 vs. 1, IQR 1-2 days; p < 0.001). Conclusion: The model accurately assesses complexity grading and full safety achievement. It can serve to predict operative time and intraoperative course, whereas no clinical correlation was found regarding postoperative outcomes. Further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Although basic laparoscopic hepatectomy (LH) has become the standard procedure for hepatectomy, the safety of advanced LH remains to be clarified, especially in elderly patients. We investigated the safety of advanced LH in elderly Japanese patients. Methods: Elderly patients (≥ 65 years) who underwent advanced LH between 2016 and 2021 were analyzed using a nationwide claims database in Japan. The perioperative outcomes of patients who underwent open hepatectomy (OH group) or LH (LH group) were compared using propensity score matching (PSM). The primary outcome was in-hospital mortality. The E-value method was performed to assess the strength of the outcome point estimates against possible unmeasured confounding factors. Results: Among 5,021 patients, eligible patients were classified into the OH (n = 4,152) and LH (n = 527) groups. The median patient age was 74 years in both groups. Hepatocellular carcinoma and metastatic liver tumors were the major indications for hepatectomy (OH: 52.5% versus 30.6%; LH: 60.7% versus 26.4%). After PSM, in-hospital mortality rates for OH and LH were 1.7 and 0.76%, respectively. The risk ratio was 0.45 (95% confidence interval, 0.16–1.25; E-value = 3.87). Compared with OH, LH was associated with a longer anesthesia time (411 versus 432 min), lower rate of blood product use (red blood concentrate: 33.5% versus 20.3%; fresh frozen plasma: 29.2% versus 17.1%), and shorter hospital stay (13 versus 12 days). Conclusions: In elderly patients, the safety of advanced LH was similar to that of advanced OH, or might be better in Japan under the current policy of hospital accreditation. [ABSTRACT FROM AUTHOR]

This study aims to explore the role of social resilience in providing community-based healthcare to older adults in Northeast Thailand during the COVID-19 pandemic. Purposive sampling was used to recruit 20 community-dwelling older adults in Maha Sarakham province, Thailand, and semi-structured interviews were conducted from 2020 to 2021. Interview transcripts were analyzed using an interpretative phenomenological analysis (IPA) approach with multiple coders to triangulate findings. The results of the IPA show that, during the pandemic, social resilience was related to social distancing, social isolation, social control, social safety, and social support. The respondents identified that providing community-based healthcare during the pandemic was associated with primary care, rehabilitative care, healthcare delivery, health behaviors, and distress intolerance. These findings highlight that social reciprocity, preventative healthcare, residential care, and good healthcare practices are important aspects of resilience among community-dwelling older adults in times of pandemic. [ABSTRACT FROM AUTHOR]

Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. Pralsetinib received approval from the United States Food and Drug Administration for the treatment of patients with metastatic RET fusion‐positive non‐small cell lung cancer (NSCLC), and received accelerated approval for the treatment of patients with RET fusion‐positive thyroid cancer. Exposure–response (ER) analyses of efficacy were performed separately in patients with thyroid cancer and in patients with NSCLC, but data for all patients were pooled for the safety analysis. ER models were developed with time‐varying exposure; the effect of covariates was also examined. For patients with NSCLC, a higher starting dose was associated with improved progression‐free survival (PFS), but this improvement did not correlate with a higher exposure overall. Significant covariates included sex and baseline Eastern Cooperative Oncology Group (ECOG) score. For patients with thyroid cancer, a higher exposure was associated with improved PFS. Significant covariates included prior systemic cancer therapy and ECOG score. For safety, higher exposure was associated with a greater risk of grade ≥3 anemia, pneumonia, and lymphopenia. Patients with an ECOG score of ≥1 had an increased risk of grade ≥3 pneumonia. Non‐White patients had a lower risk of grade ≥3 lymphopenia. ER analysis revealed that higher pralsetinib exposure was associated with improved PFS in thyroid cancer, but not in NSCLC. However, a higher starting dose (ie, 400 vs ≤300 mg daily) was correlated with better PFS for all indications. Higher exposure was also associated with an increased risk of grade ≥3 adverse events (AEs); however, the overall incidence of these events was acceptably low (≤20%). This analysis supports the use of a 400 mg starting dose of pralsetinib, allowing for dose reduction in the event of AEs. [ABSTRACT FROM AUTHOR]

In slum environments, adolescents face unique challenges that can significantly impact their well-being. This study aimed to assess the personal well-being of adolescents living in Delhi- NCR (National Capital Region) slums. Cummins' homeostasis theory states that individuals have a natural tendency to maintain a certain level of well-being and that various psychological mechanisms work to maintain this well-being within a positive and stable range. The study's objectives were to evaluate the normative range of mean scores for PWI domains, examine demographic factors influencing subjective well-being, and to evaluate the psychometric properties of the Personal Well-being Index-School Children (PWI-SC) in the context of slum-dwelling adolescents. A total of 477 slum dwelling adolescents aged 10–19 years participated in the study. The findings revealed that the PWI-SC demonstrated strong internal consistency (Cronbach's α = 0.83) and was a one-factor solution, affirming its reliability and unidimensionality as a measure of subjective well-being. The results indicated that slum-dwelling adolescents reported moderate to high levels of subjective well-being across various PWI domains. Furthermore, the regression analysis demonstrated that various domains, such as standard of living, life achievement, personal relationships, personal safety, community connectedness, and future security, significantly contribute to adolescents' overall life satisfaction. However, the impact of health is unknown in this context. Moreover, Age, family income, household size, and living conditions in the slums were identified as factors influencing subjective well-being among adolescents. Despite confronting challenging circumstances, slum-dwelling adolescents exhibit remarkable well-being, suggesting the presence of homeostatically protected moods. The validated PWI-SC has emerged as a valuable tool for future research and interventions aimed at enhancing adolescent well-being in similar contexts. [ABSTRACT FROM AUTHOR]

Modern medical devices (MMDs) are a rapidly growing field of medical technology, and recent advances have allowed them to monitor and manage patients' health remotely. As these devices become more connected in order to enhance the delivery of patient care, the concerns surrounding security, privacy, and safety are also increasing. To effectively address these concerns, "shift-left security"—which involves addressing security risks as early as possible—is becoming increasingly important. To facilitate it, threat modeling must be implemented as the first step. While various threat modeling methodologies exist, MMDs need a tailored one that can take into account the safety of patients and the complexity of a typical MMD, which contains multiple sensors and actuators. Therefore, we present a new threat modeling methodology—MEDICALHARM—tailored to identifying threats in MMD systems. MEDICALHARM delivers a holistic approach by combining threat and risk analysis under the same scheme. It specifically articulates safety threats along with security and privacy threats. Furthermore, it offers an algorithmic scheme to enable non-security experts (engineers and developers) to easily participate in the threat modeling process. To illustrate its benefits, we performed a threat modeling exercise using MEDICALHARM on a Deep Brain Stimulation device and provided an exhaustive threats document. Then, we conducted a survey among cybersecurity experts in the MMD domain to assess the MEDICALHARM. The survey results reveal positive feedback from participants, especially regarding the integration of cybersecurity, privacy, and safety, its novel trust level categorization, and the documentation strategy. The insights obtained from the questionnaire underscore MEDICALHARM's potential as a structured, inclusive threat model methodology. Then, we compared the results of this exercise with another well-known threat model scheme (STRIDE) to demonstrate MEDICALHARM's distinctive features. [ABSTRACT FROM AUTHOR]

Pivotal crash factors are investigated, and crash-severity model for the safety assessment at roundabouts and its vicinity in non-lane based heterogenous traffic is developed. An ordered-probit model was developed using crash-data collected between 2015–2019 for 20 roundabouts in India. The analysis revealed critical influencing parameters for determining the severity-level of crash outcomes at roundabouts, namely, inscribed-circle diameter, height of central island, number of circulatory lanes, presence of splitter island and median, posted-speed limit, type of collision, type of violation behaviour, collision partner, the pattern of collision, presence of road lane-marking, presence of street-light and age of victims. To precisely quantify the impact of each significant factor, marginal effects analysis was also carried out. The results show that the probability of fatal-injuries increased by 14.28% due to angle-collision, 15% for hit-pedestrians, 20.6% due to the pattern of collision and 15.60% due to the collision-partner, Whereas the probability of occurrence of grievous injury was the highest for rear-end with 17%, followed by sideswipe collision with 16% respectively. This study's findings can aid in developing effective remedies to reduce the crash severity for roundabouts road-users and updating the roundabout design standards, considering the safety perceptive. [ABSTRACT FROM AUTHOR]

Introduction: This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]). Methods: Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY). Results: A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases. Conclusion: Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified. Trial Registration: SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374. Plain Language Summary: Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis are a group of diseases that cause pain and inflammation of the joints and/or spine. Safety data were combined from five studies: two in psoriatic arthritis, two in ankylosing spondylitis, and one in non-radiographic axial spondyloarthritis. Patients were treated with upadacitinib or adalimumab for up to 5 years. Adalimumab was only used for patients participating in one of the two psoriatic arthritis studies. Side effects from treatment were more common in patients with psoriatic arthritis than those with ankylosing spondylitis and non-radiographic axial spondyloarthritis; more patients with psoriatic arthritis had side effects with upadacitinib than adalimumab. A similar number of patients across treatment groups and diseases had side effects that made them stop treatment. The number of cancer cases (except cancer of the upper layer of the skin), cardiovascular issues, and blood clots were similar between the upadacitinib and adalimumab groups in psoriatic arthritis and across diseases. Serious infections, painful rashes that cause blisters (herpes zoster, also commonly referred to as shingles), low levels of white blood cells, and cancer of the upper layer of the skin were more common with upadacitinib than adalimumab in patients with psoriatic arthritis; overall, these events occurred more often with upadacitinib in patients with psoriatic arthritis than with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Our results showed that the safety of upadacitinib was generally similar across diseases, and patients could tolerate it well for up to 5 years. No new safety risks were found with upadacitinib treatment. [ABSTRACT FROM AUTHOR]

Purpose: Seeking Safety is an evidence-based treatment for individuals with comorbid posttraumatic stress disorder and substance use disorder. This treatment shows promise to address the unique, unmet needs of women in prison. The current systematic literature review aims to highlight several critical gaps in research on Seeking Safety in forensic settings that need to be filled before Seeking Safety can be implemented in a widespread manner. Methods: PsycINFO, PubMed and Google scholar databases were used to identify studies that were published in English, included women in forensic settings, and incorporated Seeking Safety treatment. A total of seven studies met review criteria. The quality of studies was assessed with the mixed methods appraisal tool. Results: High risk of contamination, inclusion of small, predominantly White samples, high attrition rates, need for dose-response testing, and lack of follow-up data currently limit the ability to assess the efficacy of Seeking Safety in forensic settings. In addition, there is a lack of research on Seeking Safety's ability to reduce symptoms of substance use disorder for incarcerated women and further cultural adaptation may be needed. Conclusion: Seeking Safety has the potential to address the underlying causes of incarceration for justice-involved women, but additional research addressing these identified gaps is needed to facilitate more widespread implementation. [ABSTRACT FROM AUTHOR]

Introduction: Myopia and its vision-threatening complications present a significant public health problem. This review aims to provide an updated overview of the multitude of known and emerging interventions to control myopia, including their potential effect, safety, and costs. Methods: A systematic literature search of three databases was conducted. Interventions were grouped into four categories: environmental/behavioral (outdoor time, near work), pharmacological (e.g., atropine), optical interventions (spectacles and contact lenses), and novel approaches such as red-light (RLRL) therapies. Review articles and original articles on randomized controlled trials (RCT) were selected. Results: From the initial 3224 retrieved records, 18 reviews and 41 original articles reporting results from RCTs were included. While there is more evidence supporting the efficacy of low-dose atropine and certain myopia-controlling contact lenses in slowing myopia progression, the evidence about the efficacy of the newer interventions, such as spectacle lenses (e.g., defocus incorporated multiple segments and highly aspheric lenslets) is more limited. Behavioral interventions, i.e., increased outdoor time, seem effective for preventing the onset of myopia if implemented successfully in schools and homes. While environmental interventions and spectacles are regarded as generally safe, pharmacological interventions, contact lenses, and RLRL may be associated with adverse effects. All interventions, except for behavioral change, are tied to moderate to high expenditures. Conclusion: Our review suggests that myopia control interventions are recommended and prescribed on the basis of accessibility and clinical practice patterns, which vary widely around the world. Clinical trials indicate short- to medium-term efficacy in reducing myopia progression for various interventions, but none have demonstrated long-term effectiveness in preventing high myopia and potential complications in adulthood. There is an unmet need for a unified consensus for strategies that balance risk and effectiveness for these methods for personalized myopia management. [ABSTRACT FROM AUTHOR]

Background Schools with formal sun safety polices generally show better sun safety practices than schools without. Objectives To understand the extent to which Welsh primary schools have sun safety policies; to identify the key characteristics of policies; to assess whether policy adoption varies by school characteristics; and to consider what support schools need to develop sun safety policies. Methods An online multiple-choice survey on sun safety was distributed to all 1241 primary schools in Wales. Results In total, 471 (38.0%) schools responded. Of these, 183 (39.0%) reported having a formal sun safety policy. Welsh medium schools (P = 0.036) and schools in North Wales (P = 0.008) were more likely to report having a policy. Schools with a higher percentage of pupils receiving free school meals (P = 0.046) and with lower attendance rates (P = 0.008) were less likely to report having a sun safety policy. The primary reasons for schools not having a policy included being 'not aware of the need' (34.6%); 'need assistance with policy or procedure development' (30.3%); and 'not got around to it just yet' (26.8%). Conclusions With less than half of schools reporting a sun safety policy and variation in the presence/absence of a policy by school characteristics, our survey revealed inconsistency in formal sun safety provision in Welsh schools. The findings also suggest that schools are unaware of the importance of sun safety and need support to develop and implement policies. This snapshot of the current situation in primary schools in Wales provides a basis upon which the comprehensiveness, effectiveness and implementation of sun safety policies can be further evaluated. [ABSTRACT FROM AUTHOR]

Objective: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. Methods: A multicenter, randomized, assessor‐blind and parallel‐controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I–II) facial acne vulgaris were recruited in this study over a 16‐week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre‐ and post‐treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. Results: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. Conclusion: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris. [ABSTRACT FROM AUTHOR]

There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates. A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days. Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates. The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. We conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. In total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. This study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations. • DOACs may be implicated in DDIs with significant clinical relevance. • Skilled drug interaction management is thus essential to ensure safe use of DOACs. • Studies on DDI management with DOACs in real-life ambulatory care are lacking. • We conducted an intervention study in over 200 community pharmacies in Belgium. • Active DDI management significantly impacted DOAC pharmacotherapy. [ABSTRACT FROM AUTHOR]

The increasing incidence of lung cancer diagnosis during pregnancy has brought new challenges and opportunities to expand the knowledge gap in this protected patient population. Here, available data and top recommendations for the practicing oncologist are discussed. [ABSTRACT FROM AUTHOR]

Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle—Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD50) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling. Several methods, which have been devised to determine the LD50, are faced with the challenge of using a large number of animals and time constraints. Despite the inherent advantage of the newer OECD Test Guidelines, the increasing concerns among toxicologists, the regulatory authorities and the general public, on the need to adhere to 3Rs principle, necessitated the need for an improved approach. Such an approach should not only minimize the time and number of animals required, but also take into cognizance animal welfare, and give accurate, comparable, and reproducible results across laboratories. While taking advantage of the inherent merits of the existing methods, here is presented the mathematical basis and evaluation of an improved method for toxicity profiling of test substances and estimation of LD50. The method makes use of the generated Table of values for the selection of appropriate test doses. Our proposed method has capacities to optimize the time and number of animal use, ensure more reliable and reproducible results across laboratories, allow for easy selection of doses for subsequent toxicity profiling, and be adaptable to other biological screening beyond toxicity studies. [ABSTRACT FROM AUTHOR]

This paper examines whether, following a prolonged health crisis, the offer of a tourist destination coupled with the use of health and safety protocols at the destination, influences brand equity and intention to visit. Specifically, it (a) examines whether the indoor/outdoor activity offers influence brand equity and intention to visit, (b) demonstrates whether health and safety protocols influence brand equity and intention to visit, and (c) tests whether there is a moderating effect by the use of health and safety protocols in destinations specializing in indoor, rather than outdoor, activities. The study is based on an experimental design in which the type of offer (out/indoor activities) and the use of anti-covid protocols versus their non-use were manipulated. [ABSTRACT FROM AUTHOR]

Background Study: Virtual reality (VR) is becoming a popular technology for safety training in construction. Several VR training prototypes have been designed and tested, which show they can perform better than traditional training tools. However, most of these existing tools are not underpinned by clear pedagogical theory, and studies assessing the impact of pedagogical theories on the effectiveness of VR prototypes are still rare in the literature. Objectives: This study aims to investigate if and how the productive failure theory and the directive instruction theory have an impact on the effectiveness of VR safety training for confined space workers. Methods: The study used a randomized controlled method involving 74 participants. The effectiveness of these two training methods was assessed in terms of knowledge acquisition and retention. Results and Conclusions: The results illustrate that the productive failure training design performed better in terms of knowledge acquisition and retention. This paper introduces the Productive Failure Theory and shows the great potential of this approach for self‐service VR safety training in the field of construction. Lay Description: What is already known about this topic: PF has been proven effective in classroom‐based teaching practice.PF has been proven effective in non‐immersive virtual training.DI is a commonly used pedagogical method for VR training. What this paper adds: The present paper investigates the feasibility of applying PF theory in VR safety training.The present paper examines the pedagogical impacts of the two pedagogical approaches within VR serious games. Implications for practice and/or policy: PF can be applied to self‐help VR safety training, reducing the demand for resources such as teaching staff and venues.PF training design performed better in terms of knowledge acquisition and retention.PF has great potential for self‐help VR safety training in various fields. [ABSTRACT FROM AUTHOR]

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers. Synopsis: Newborns/infants remain at high risk for severe morbidity/mortality from pertussis infection. Vaccination in pregnancy has become a key strategy to reduce this serious and potentially fatal disease. Herein, we focus on vaccination challenges and strategies for obstetric and gynecologic health care providers. [ABSTRACT FROM AUTHOR]

Objective: Traditional masculinity norms displayed by men attempt to signal a dominance or 'toughness' to others; however, traditional masculine norms are associated with a range of mental health difficulties, including depression and anxiety. Based on social rank theory, we tested the mediating role of insecure striving, social safeness and fears of compassion on the relationship between masculinity, anxiety and depression. We also examined whether compassionate goals were negatively correlated with masculine norm adherence. Design: We used a cross‐sectional survey design recruiting 844 men, aged 18–60 years (M = 34.0, SD = 14.4). Results: Our results replicated previous findings with masculine norms significantly associated with depression and anxiety. Extending on previous work, we found insecure striving, social safeness and fears of compassion fully mediated these relationships for anxiety and partially for depression. This relationship was strongest for the masculinity subtypes of self‐reliance and emotional control. Compassionate goals were negatively associated with masculine norm adherence. Conclusions: Social rank theory offers a helpful explanatory framework to understand the links between traditional masculinity and mental health, highlighting the importance of social safeness and insecure striving for men. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the effects of a comprehensive traffic safety policy—New York City's (NYC's) 2014 Vision Zero—on the health of Medicaid enrollees. Methods. We conducted difference-in-differences analyses using individual-level New York Medicaid data to measure traffic injuries and expenditures from 2009 to 2021, comparing NYC to surrounding counties without traffic reforms (n = 65 585 568 person-years). Results. After Vision Zero, injury rates among NYC Medicaid enrollees diverged from those of surrounding counties, with a net impact of 77.5 fewer injuries per 100 000 person-years annually (95% confidence interval = −97.4, −57.6). We observed marked reductions in severe injuries (brain injury, hospitalizations) and savings of $90.8 million in Medicaid expenditures over the first 5 years. Effects were largest among Black residents. Impacts were reversed during the COVID-19 period. Conclusions. Vision Zero resulted in substantial protection for socioeconomically disadvantaged populations known to face heightened risk of injury, but the policy's effectiveness decreased during the pandemic period. Public Health Implications. Many cities have recently launched Vision Zero policies and others plan to do so. This research adds to the evidence on how and in what circumstances comprehensive traffic policies protect public health. (Am J Public Health. 2024;114(6):633–641. https://doi.org/10.2105/AJPH.2024.307617) [ABSTRACT FROM AUTHOR]

Background and purpose: Cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited. Methods: This retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2‐year course of cladribine treatment. The primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2‐year treatment course. Results: A total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. The study found a significant reduction in annualized relapse rate at the 12‐month follow‐up after cladribine completion compared to the year prior to starting therapy (0.07 ± 0.25 vs. 0.82 ± 0.80, p < 0.001). Furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. The safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event. Conclusions: This study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. Real‐world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. However, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long‐term impact are necessary. [ABSTRACT FROM AUTHOR]

Propofol has a favourable efficacy profile in gastrointestinal endoscopic procedures, however adverse events remain frequent. Emerging evidence supports remimazolam use in gastrointestinal endoscopy. This systematic review and meta-analysis compares remimazolam and propofol, both combined with a short-acting opioid, for sedation of adults in gastrointestinal endoscopy. We searched MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing efficacy-, safety-, and satisfaction-related outcomes between remimazolam and propofol, both combined with short-acting opioids, for sedation of adults undergoing gastrointestinal endoscopy. We performed sensitivity analyses, subgroup assessments by type of short-acting opioid used and age range, and meta-regression analysis using mean patient age as a covariate. We used R statistical software for statistical analyses. We included 15 trials (4516 subjects). Remimazolam was associated with a significantly lower sedation success rate (risk ratio [RR] 0.991; 95% confidence interval [CI] 0.984–0.998; high-quality evidence) and a slightly longer induction time (mean difference [MD] 9 s; 95% CI 4–13; moderate-quality evidence), whereas there was no significant difference between the sedatives in other time-related outcomes. Remimazolam was associated with significantly lower rates of respiratory depression (RR 0.41; 95% CI 0.30–0.56; high-quality evidence), hypotension (RR 0.43; 95% CI 0.35–0.51; moderate-quality evidence), hypotension requiring treatment (RR 0.25; 95% CI 0.12–0.52; high-quality evidence), and bradycardia (RR 0.42; 95% CI 0.30–0.58; high-quality evidence). There was no difference in patient (MD 0.41; 95% CI –0.07 to 0.89; moderate-quality evidence) and endoscopist satisfaction (MD –0.31; 95% CI –0.65 to 0.04; high-quality evidence) between both drugs. Remimazolam has clinically similar efficacy and greater safety when compared with propofol for sedation in gastrointestinal endoscopies. [ABSTRACT FROM AUTHOR]

Risk‐based techniques such as risk graph and Layer of Protection Analysis (LOPA) are used to determine the Safety Integrity Level (SIL) of safety instrumented functions to ensure that risk is reduced to a tolerable level. However, these techniques have some drawbacks. For instance, they need absolute and precise numbers to evaluate SIL parameters, which are rarely available or are highly uncertain. In addition, they are incapable of considering individual and societal risks simultaneously. Moreover, risk tolerance criteria are likely to be used incorrectly in the LOPA technique, and risk graph is difficult to calibrate. In the current paper, a novel comprehensive fuzzy arithmetic model has been developed to determine the required SILs in process industries. The fuzzy required Risk Reduction Factor (RRF) is calculated for both individual and societal risks. Fuzzy numbers are developed from crisp intervals, based on the expected interval of the fuzzy numbers. Expert fuzzy‐scaled elicitation has been applied to obtain the SIL parameters. In the proposed model, the overall risk tolerance criterion and apportionment factor are defined as SIL parameters for both individual and societal risks to ensure that the applied risk criteria are compliant with the requirements of the system. In addition, an approach is introduced for determining the required SIL based on the fuzzy required RRF. The proposed methodology was demonstrated to alleviate the limitations, and thus, can be considered as a more precise alternative to the conventional methods. [ABSTRACT FROM AUTHOR]

Image-based sexual abuse (IBSA) encompasses the taking, sharing, and/or threatening to share nude or sexual images of others without their consent. The prevalence of IBSA is growing rapidly due to technological advancements, such as access to smartphones, that have made engagement in such activities easier. Bystanders offer an important means of intervention, but little is known about what facilitates or inhibits bystander action in these contexts. To address this gap in the literature, seven focus groups (n = 35) were conducted to explore the factors that facilitate and inhibit bystander action in the context of three different IBSA scenarios (taking, sharing, and making threats to share nude or sexual images without consent). Using thematic analysis, eight themes were identified, suggesting that the perceived likelihood of intervention increased with greater feelings of responsibility, empathy with the victim, reduced feelings of audience inhibition, greater feelings of safety, greater anger toward the IBSA behavior, closer relationships with the victim and perpetrator, the incident involving a female victim and male perpetrator, and perception of greater benefits of police involvement. These findings are considered alongside the physical sexual violence literature in highlighting the similarities and nuances across the different contexts. Implications for the development of policies and educational materials are discussed in relation to encouraging greater bystander intervention in IBSA contexts. [ABSTRACT FROM AUTHOR]

Accessible Summary: What is known on the subject?: Nurses' observation of patients in seclusion is essential to ensure patient safety.Patient observation in seclusion assists nurses in adhering to the requirements of mental health legislation and hospital policy.Direct observation and video monitoring are widely used in observing patients in seclusion.Coercive practices may cause distress to patient‐staff relations. What the paper adds to existing knowledge?: We add detailed information on specific observation methods in seclusion and compare them from the perspective of patients.Nurses communicating with patients ensures relational contact and that quality care is provided to patients even in the most distressed phase of their illness.Providing prior information to patients on observation methods in seclusion and the need for engaging patients in meaningful activities, while in seclusion are emphasized.Observation via camera and nurses' presence near the seclusion room made patients feel safe and gave a sense of being cared for in seclusion.Pixellating the video camera would give a sense of privacy and dignity. What are the implications for practice?: The overarching goal is to prevent seclusion. However, when seclusion is used as a last resort to manage risk to others, it should be done in ways that recognize the human rights of the patient, in ways that are least harmful, and in ways that recognize and cater to patients' unique needs.A consistent approach to relational contact and communication is essential. A care plan must include patient's preferred approach for interacting while in seclusion to support individualized care provision.Viewing panels (small window on the seclusion door) are important in establishing two‐way communication with the patient. Educating nurses to utilize them correctly helps stimulate relational contact and communication during seclusion to benefit patients.Engaging patients in meaningful activities when in seclusion is essential to keep them connected to the outside world. Depending on the patient's presentation in the seclusion room and their preferences for interactions, reading newspapers, poems, stories, or a book chapter aloud to patients, via the viewing panel could help ensure such connectedness.More focus should be placed on providing communication training to nurses to strengthen their communication skills in caring for individuals in challenging care situations.Patient education is paramount. Providing prior information to patients using a co‐produced information leaflet might reduce their anxiety and make them feel safe in the room.When using cameras in the seclusion room, these should be pixelated to maintain patients' privacy. Introduction: A lack of research investigating the specific role that various observational techniques may have in shaping the therapeutic relations in mental health care during seclusion warranted this study. Aim: The aim of the study was to explore patients' experience of different methods of observation used while the patient was in seclusion. Method: A retrospective phenomenological approach, using semi‐structured interviews, ten patients' experiences of being observed in the seclusion room was investigated. Colaizzi's descriptive phenomenological method was followed to analyse the data. Results: Communicating and engaging patients in meaningful activities can be achieved via the viewing panel. The camera was considered essential in monitoring behaviour and promoting a sense of safety. Pixelating the camera may transform patient view on privacy in seclusion. Discussion: The mental health services must strive to prevent seclusion and every effort should be made to recognise the human rights of the patient. The study reveals numerous advantages when nurses actively engage in patient communication during the process of observation. Implications for Practice: Different observation methods yield different benefits; therefore, staff education in using these methods is paramount. Empowering the patient with prior information on seclusion, engaging them in meaningful activities and proper documentation on patient engagement, supports the provision of individualised care in seclusion. [ABSTRACT FROM AUTHOR]

In this work, we address the problem of damage diagnosis on the railway pantograph mechanism including nonlinear behaviour and sample-induced uncertainties. In particular, we discuss an experimental campaign in which investigation pursued the analysis of frequency response functions estimated by a dedicated inspection robot that we intentionally developed for vibration tests on pantographs. Special focus is pointed to the inherent nonlinear behaviour of the pantograph for which we estimated the damage index for different levels of the input excitation. The investigation is carried out on a population of pantographs of the same type and studying three kinds of damages. Results highlight the relevance of including several excitation levels and encourage investigation in a real operational scenario. [ABSTRACT FROM AUTHOR]

To compare the safety and efficacy of the Preserflo Microshunt with trabeculectomy in the treatment of patients with glaucoma. A systematic review and meta‐analysis was conducted. The primary outcome measures recorded as a measure of efficacy of the interventions were intra‐ocular pressure (IOP) at final follow‐up and IOP reduction (IOPR). Secondary outcomes recorded to measure efficacy were reduction in the number of glaucoma medications and reinterventions. To assess safety profile, the proportions of patients with post‐operative complications were recorded. Seven articles were included in this study. A total of 1353 eyes were included in this review (Preserflo: 812, trabeculectomy: 541). Post‐operative IOP (mean difference [MD] = 0.78 [0.66, 0.90], p < 0.001) results are significantly lower for trabeculectomy than Preserflo. The IOPR (MD = −1.20 [−2.30, −0.09], p = 0.034) results significantly favour trabeculectomy over Preserflo Microshunt. The reduction in topical glaucoma medications (MD = −0.32 [−0.58, −0.07], p = 0.014) is significantly higher for trabeculectomy. There is no statistically significant difference in levels of hypotony (risk ratio [RR] = −0.05 [−0.47, 0.37], p = 0.806), choroidal effusion/detachment (RR = −0.12 [−0.42, 0.19], p = 0.444), hyphaema (RR = 0.20 [−0.11, 0.51], p = 0.216) and flat anterior chamber (RR = 0.49 [−1.02, 0.03], p = 0.066). There are significantly more bleb‐related complications in the trabeculectomy groups than Preserflo groups (RR = −0.63 [−1.01, −0.24], p = 0.001). There were statistically more reinterventions required in the trabeculectomy groups than Preserflo groups (RR = −0.48 [−0.65, −0.30], p < 0.001). Compared to trabeculectomy, the Preserflo Microshunt is not as effective in lowering intra‐ocular pressure, has a similar safety profile and has a lower reintervention rate. Further research is required given the lack of randomised controlled trials within this study and resulting low strength of evidence. [ABSTRACT FROM AUTHOR]

Domestic workers (DWs) are integral to the daily lives of a significant portion of India's urban population, with an estimated 3.9 million individuals employed in domestic roles in urban areas, mostly women. This article explores the perceptions of home, house, and safe spaces among migrant women DWs in Delhi. Through in-depth interviews, it delves into their lived experiences as both breadwinners and survivors of domestic violence, revealing that (a) house and home are differently conceptualized by these workers; (b) their homes are perceived as warzones, reinforcing patriarchy through incidents of domestic violence and gendered subordination; and (c) women DWs navigate the complexities of conflicting identities as breadwinners and survivors within unequal gendered relationships. [ABSTRACT FROM AUTHOR]

Background: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge worldwide. Here, we introduced a phase I trial of autologous RAK cell therapy in patients with mRCC whose cancers progressed after prior systemic therapy. Although RAK cells have been used in clinic for many years, there has been no dose-escalation study to demonstrate its safety and efficacy. Methods: We conducted a phase I trial with a 3 + 3 dose-escalation design to investigate the dose-related safety and efficacy of RAK cells in patients with mRCC whose cancers have failed to response to systemic therapy (ChiCTR1900021334). Results: Autologous RAK cells, primarily composed of CD8+ T and NKT cells, were infused intravenously to patients at a dose of 5 × 109, 1 × 1010 or 1.5 × 1010 cells every 28 days per cycle. Our study demonstrated general safety of RAK cells in a total of 12 patients. Four patients (33.3%) showed tumor shrinkage, two of them achieved durable partial responses. Peripheral blood analysis showed a significant increase in absolute counts of CD3+ and CD8+ T cells after infusion, with a greater fold change observed in naive CD8+ T cells (CD8+CD45RA+). Higher peak values of IL-2 and IFN-γ were observed in responders after RAK infusion. Conclusion: This study suggests that autologous RAK cell immunotherapy is safe and has clinical activity in previously treated mRCC patients. The improvement in peripheral blood immune profiling after RAK cell infusion highlights its potential as a cancer treatment. Further investigation is necessary to understand its clinical utility. [ABSTRACT FROM AUTHOR]

Existing approaches to infrastructure management neglect the impact of infrastructure condition on safety performance, even though poorly maintained roadways can contribute to increased crash frequencies. This is perhaps because very few studies have quantified the impact of infrastructure condition on safety performance. Hence, this work develops safety performance function (SPF) models that relate pavement condition—specifically, roughness, as measured using the international roughness index (IRI)—and other roadway factors with observed crash frequencies. These SPFs are then combined with pavement roughness deterioration models to better understand how maintenance decisions can be used to improve roadway safety performance. Data from two-lane rural roadways in Pennsylvania are used for this effort. The SPF estimation results reveal that accounting for IRI in SPF development significantly improves model fit, and that IRI has a significant and positive impact on crash outcomes. The results further suggest that the IRI has a different impact on total crash frequency as compared to fatal and injury crash frequency, and rear-end crashes. This is likely due to how roughness of the roadway can impact travel speeds. Finally, the results also show that maintenance activities that reduce IRI can have significant safety benefits. This suggests that pavement management decisions should also consider the anticipated safety benefits, in addition to other factors. [ABSTRACT FROM AUTHOR]

Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding. The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection. Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days. Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV. [ABSTRACT FROM AUTHOR]

Background: Illicit substance sales facilitated by social media platforms are a growing public health issue given recent increases in overdose deaths, including an alarming rise in cases of fentanyl poisoning. However, little is known about how online users evaluate what features of social media posts convey safety, which can influence their intent to source illicit substances. Objectives: This study adapts conjoint analysis which assessed how attributes of social media posts (i.e., features) influence safety evaluations of mock posts selling illicit substances. 440 participants were recruited online for self-reporting use or purchase of controlled substances or prescription medicines recreationally. The following attributes were tested: drug packaging, drug offerings, profile photo of seller, payment info provided, and use of emojis. Results: Packaging was ranked the most important attribute (Average Importance =43.68, Offering=14.94, Profile=13.86, Payment=14.11, Emoji=13.41), with posts that displayed drugs in pill bottles assessed as the most safe. Attribute levels for advertising multiple drugs, having a blank profile photo, including payment information, and including emojis also ranked higher in perceived safety. Rankings were consistent across tested demographic factors (i.e., gender, age, and income). Survey results show that online pharmacies were most likely to be perceived as safe for purchasing drugs and medications. Additionally, those who were younger in age, had higher income, and identified as female were more likely to purchase from a greater number of platforms. Conclusions: These findings can assist in developing more precise content moderation for platforms seeking to address this ongoing threat to public safety. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and safety of different dosage regimens of zuranolone in the treatment of patients with major depressive disorder (MDD). PubMed, Embase, The Cochrane Library and other databases were searched from inception until July 2019. Randomized controlled trials (RCTs) related to the efficacy and safety of zuranolone in the treatment of MDD were included. The data were extracted independently by 2 investigators and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcome includes the 17-item HAMILTON total score (HAMD-17) and the incidence of adverse events (AEs). Six high-quality RCTs with 1593 patients were finally included in our analysis. Zuranolone group achieve a notable treatment effect at day15 in HAMD-17 compared with placebo group (MD = −2.69, 95 % CI: −4.45 to −0.94, P < 0.05). For safety, no significant differences existed in the proportion of patients with AEs between zuranolone with placebo (RR = 1.25, 95 % CI: 0.99 to 1.58, P = 0.06). Zuranolone has a significant efficacy in improving depressive symptoms in the short term and is positively correlated with the dosage administered. However, the efficacy of zuranolone decreased significantly when the time of administration was extended. Zuranolone demonstrated a controllable safety issue. But adverse effects increased as the dose of zuranolone was gradually increased to 50 mg. • It is the further meta-analysis to study different dosage regimens of zuranolone in the treatment of major depressive disorder. • Zuranolone can effectively improve depressive symptoms in the short term. • With increasing doses of zuranolone, it also increases the incidence of adverse events. [ABSTRACT FROM AUTHOR]

The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment. Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs). Design: Meta-analysis of RCTs. Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions. Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66–3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary. Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design. Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621). [ABSTRACT FROM AUTHOR]

Background: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. Methods: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18–75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. Results: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 μg*h/mL, and AUC0-inf ranged from 159 to 340 μg*h/mL. TG103 had a half-life of 110–116 h, with a median Tmax of 36–48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. Conclusions: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. Trial registration: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion In the development of eye and face protection standards against biological hazards, it is important to consider that the eye and face protectors may be used in the outdoor environment, where ultraviolet (UV) exposure from the sun is much higher than indoors. Workers affected include paramedics, ambulance officers and clinical testing personnel.Spectral transmittances (280–780 nm) were measured on eight face shields and one goggle of the types used in hospital and clinical environments, three overhead projector sheets and an occupational impact protective goggle. The UV and luminous transmittances were calculated according to the international and two national sunglass standards, and compared with the compliance requirements.All the face shields and goggle lenses were made of variants of the same material. All the samples, including the overhead projector sheets, complied with the requirements of the sunglass standards (for normal conditions, in the case of the American standard).Since all the lenses complied with the sunglass standards for UV protection, and there appears to be uniformity in the choice of materials in this product type, there is no need to make provision, as is the case for occupational eye and face protection standards, for protectors that do not provide UV protection. This makes labelling and advice to end users from eyecare and safety professionals much simpler. [ABSTRACT FROM AUTHOR]