Safe and just Earth system boundaries.

The stability and resilience of the Earth system and human well-being are inseparably linked1-3, yet their interdependencies are generally under-recognized; consequently, they are often treated independently4,5. Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice)4. The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future.

Dense reinforcement learning for safety validation of autonomous vehicles.

One critical bottleneck that impedes the development and deployment of autonomous vehicles is the prohibitively high economic and time costs required to validate their safety in a naturalistic driving environment, owing to the rarity of safety-critical events1. Here we report the development of an intelligent testing environment, where artificial-intelligence-based background agents are trained to validate the safety performances of autonomous vehicles in an accelerated mode, without loss of unbiasedness. From naturalistic driving data, the background agents learn what adversarial manoeuvre to execute through a dense deep-reinforcement-learning (D2RL) approach, in which Markov decision processes are edited by removing non-safety-critical states and reconnecting critical ones so that the information in the training data is densified. D2RL enables neural networks to learn from densified information with safety-critical events and achieves tasks that are intractable for traditional deep-reinforcement-learning approaches. We demonstrate the effectiveness of our approach by testing a highly automated vehicle in both highway and urban test tracks with an augmented-reality environment, combining simulated background vehicles with physical road infrastructure and a real autonomous test vehicle. Our results show that the D2RL-trained agents can accelerate the evaluation process by multiple orders of magnitude (103 to 105 times faster). In addition, D2RL will enable accelerated testing and training with other safety-critical autonomous systems.

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations.

Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of safety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2 h session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals.

Are there any good experiments that should not be done?

Is there any research that should not be done? Could you think of an experiment and then decide not to do it? These questions get to the heart of the power of modern genetics to mix up and alter genes.

One Step Closer to Safer: Counseling Outcomes from American Academy of Pediatrics Firearm Safe Storage Education Training.

OBJECTIVE: To assess pre and postself-reported counseling outcomes for Safer: Storing Firearms Prevents Harm, an American Academy of Pediatrics universal firearm safe storage counseling training for pediatric clinicians providing health maintenance in outpatient settings. STUDY DESIGN: Safer was developed by a national multidisciplinary committee of firearm injury prevention experts with input from firearm-owning families and launched in June 2021. Pediatric clinicians completed baseline and 1-month posttraining surveys after signing up for the Pedialink course from February through June 2022. Primary outcomes included self-reported measures of counseling self-efficacy and frequency. Wilcoxon matched-pairs signed-rank tests compared outcome distributions at baseline and follow-up. Two adjusted, multilevel mixed-effects regression models were conducted. RESULTS: Of 230 clinicians who completed baseline surveys, 146 (64%) completed 1-month postsurveys. Regional representation included Southeast = 67 (46%), Northeast = 24 (16%), Midwest = 21 (14%), Pacific = 15 (10%), Southwest = 11 (8%), and Rocky Mountain = 8 (5%). At follow-up, there was significant improvement in both the distribution of self-efficacy (median [first Quartile-third Quartile = 50 [20-70] at baseline and 80 [60-85] at follow-up; P < .001) and self-reported counseling frequency (median [first Quartile-third Quartile] = 10 [0-50] at baseline and 50 [10-80] at follow-up; P < .001). Adjusted regression model results suggested that self-efficacy significantly improved from baseline to follow-up (time coefficient 25.3; 95% CI = [21.0, 29.5]; P < .001) as did counseling frequency (time coefficient 13.6; 95% CI = [9.2, 18.0]; P < .001). CONCLUSIONS: Significant improvement in self-reported counseling self-efficacy and frequency was demonstrated 1 month following Safer training.

Guardians of precision: advancing radiation protection, safety, and quality systems in nuclear medicine.

BACKGROUND: In the rapidly evolving field of nuclear medicine, the paramount importance of radiation protection, safety, and quality systems cannot be overstated. This document provides a comprehensive analysis of the intricate regulatory frameworks and guidelines, meticulously crafted and updated by national and international regulatory bodies to ensure the utmost safety and efficiency in the practice of nuclear medicine. METHODS: We explore the dynamic nature of these regulations, emphasizing their adaptability in accommodating technological advancements and the integration of nuclear medicine with other medical and scientific disciplines. RESULTS: Audits, both internal and external, are spotlighted for their pivotal role in assessing and ensuring compliance with established standards, promoting a culture of continuous improvement and excellence. We delve into the significant contributions of entities like the International Atomic Energy Agency (IAEA) and relevant professional societies in offering universally applicable guidelines that amalgamate the latest in scientific research, ethical considerations, and practical applicability. CONCLUSIONS: The document underscores the essence of international collaborations in pooling expertise, resources, and insights, fostering a global community of practice where knowledge and innovations are shared. Readers will gain an in-depth understanding of the practical applications, challenges, and opportunities presented by these regulatory frameworks and audit processes. The ultimate goal is to inspire and inform ongoing efforts to enhance safety, quality, and effectiveness in nuclear medicine globally.

Major Traffic Safety Reform and Road Traffic Injuries Among Low-Income New York Residents, 2009-2021.

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).

Firearm Storage Behaviors - Behavioral Risk Factor Surveillance System, Eight States, 2021-2022.

Secure firearm storage might help reduce access by children and other unauthorized users and the related risk for injury or death. Information about state-specific prevalence of firearm storage practices can be used to develop secure storage messages and programs; however, such information is often unavailable. Data from the Behavioral Risk Factor Surveillance System, by respondent characteristics, were used to estimate prevalence of keeping firearms in or around the home and related storage practices for eight states that administered the firearm safety module in 2021 or 2022. Overall, 18.4% (California) to 50.6% (Alaska) of respondents reported that a firearm was kept in or around their home. Among those with a firearm in or around the home, 19.5% (Minnesota) to 43.8% (North Carolina) reported that a firearm was stored loaded. Across all eight states, approximately one half of those with a loaded firearm stored at least one loaded firearm unlocked. Among respondents with a child and a loaded firearm in the home, 25.2% (Ohio) to 41.4% (Alaska) reported that a loaded firearm was stored unlocked. Variability in firearm storage practices highlights the importance of local data and suggests opportunities to tailor prevention efforts to specific population groups to reduce risk for firearm handling by children without adult supervision, and other unauthorized persons.

A Qualitative Exploration of the Built Environment as a Key Mechanism of Safety and Social Cohesion for Youth in High-Violence Communities.

The characteristics of a neighborhood's built environment may influence health-promoting behaviors, interactions between neighbors, and perceptions of safety. Although some research has reported on how youth in high-violence communities navigate danger, less work has investigated how these youth perceive the built environment, their desires for these spaces, and how these desires relate to their conceptions of safety and perceptions of other residents. To fill this gap, this study used focus group data from 51 youth ages 13-24 living in New Orleans, Louisiana. Four themes were developed using reflexive thematic analysis: community violence is distressing and disruptive, youth use and want to enjoy their neighborhood, systemic failure contributes to negative outcomes, and resources and cooperation create safety. This analysis indicates that young people desire to interact with the built environment despite the threat of community violence. They further identified built environment assets that facilitate socialization and recreation, such as local parks, and social assets in the form of cooperation and neighbor-led civic engagement initiatives. In addition, the youth participants demonstrated awareness of structural inequities that influence neighborhood health and violence-related outcomes. This study contributes to efforts to understand how youth with high levels of community violence exposure understand and interact with the built and social environments.

Neighborhood Safety and Neighborhood Police Violence Are Associated with Psychological Distress among English- and Spanish-Speaking Transgender Women of Color in New York City: Finding from the TURNNT Cohort Study.

Transgender women of color (TWOC) experience high rates of police violence and victimization compared to other sexual and gender minority groups, as well as compared to other White transgender and cisgender women. While past studies have demonstrated how frequent police harassment is associated with higher psychological distress, the effect of neighborhood safety and neighborhood police violence on TWOC's mental health is rarely studied. In this study, we examine the association between neighborhood safety and neighborhood police violence with psychological distress among TWOC. Baseline self-reported data are from the TURNNT ("Trying to Understand Relationships, Networks and Neighborhoods among Transgender Woman of Color") Cohort Study (analytic n = 303). Recruitment for the study began September 2020 and ended November 2022. Eligibility criteria included being a TWOC, age 18-55, English- or Spanish-speaking, and planning to reside in the New York City metropolitan area for at least 1 year. In multivariable analyses, neighborhood safety and neighborhood police violence were associated with psychological distress. For example, individuals who reported medium levels of neighborhood police violence had 1.15 [1.03, 1.28] times the odds of experiencing psychological distress compared to those who experienced low levels of neighborhood police violence. Our data suggest that neighborhood safety and neighborhood police violence were associated with increased psychological distress among TWOC. Policies and programs to address neighborhood police violence (such as body cameras and legal consequences for abusive officers) may improve mental health among TWOC.

Safety of biliary drainage with 6-mm metallic stent for preoperative obstructive jaundice in pancreatic cancer: PURPLE SIX STUDY.

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

A Pilot Randomized Trial Evaluating the Cool 2 Be Safe Junior Playground Safety Program for Preschool Children.

OBJECTIVE: Unintentional injury is the leading cause of death to children worldwide, and playgrounds pose a significant risk of injury. Those aged 5 and 6 years are particularly vulnerable to playground injuries. Previous interventions have typically targeted environmental modifications or increased supervision to reduce playground injuries; however, minimal research has focused on implementing behavioral interventions that seek to change children's safety knowledge and risk-taking behaviors on the playground. The current randomized trial addressed these gaps in the literature and sought to increase preschool children's hazard awareness skills and knowledge of unsafe playground behaviors and decrease their intentions to engage in risk-taking behaviors on the playground. METHOD: A total of 77 children aged 5 and 6 years were tested at a laboratory on a university campus, using a parallel group design, with 38 randomized to the playground intervention group and 39 randomly assigned to a control group. The intervention was manualized and delivered to small groups of children (3-5) over several sessions. RESULTS: Statistical analyses revealed significant group differences. Intervention experience led to significant increases in hazard awareness skills and knowledge of unsafe playground behaviors, and significant decreases in children's risk-taking behavioral intentions, whereas those in the control group showed no significant changes in these scores. Attention scores for those in the intervention group highlighted that the program content was successful in maintaining children's attention and engagement, and memory scores indicated excellent retention of lesson content. CONCLUSION: The program shows promise in addressing the issue of unintentional playground injuries in young children.

A Feasibility Randomized Trial Evaluating Safe Peds: A Virtual Reality Training Program to Teach Children When to Cross Streets Safely.

OBJECTIVE: Injury as pedestrians is a leading contributor to childhood deaths. This study evaluated the effectiveness of Safe Peds, a fully immersive virtual reality training program to teach children when to cross street safely, with the focus on a number of foundational skills and practicing these in traffic situations of varying complexity. METHODS: Children 7-10 years old were randomly assigned to a control (N = 31) or intervention (N = 26) group. Eligibility criteria included English speaking and typically developing. Testing took place on campus. All children completed pre- and post-testing measures, with those in the intervention group receiving training in between. Training comprised 1 session with 3 phases for a total of up to 1.5 hr and was tailored to each child's performance over trials. On each trial, children decided when to cross and fully executed this crossing, with measures automatically taken by the system as they did so. RESULTS: Negative binomial regression and analysis of covariance tests were applied, predicting post-test scores while controlling for pre-test scores, age, and sex. The intervention was effective in improving children's street crossing skills, including stopping and checking skills (stop at the curb, look left/right/left, check for traffic before crossing the yellow line), and choosing safe inter-vehicle gaps. Children in the control group did not show significant improvements in any crossing skills. CONCLUSIONS: The Safe Peds program effectively teaches children skills to support their deciding when to safely cross in a variety of traffic situations. Implications for pedestrian injury are discussed.

Teaching children pedestrian safety in virtual reality via smartphone: a noninferiority randomized clinical trial.

OBJECTIVE: To evaluate whether child pedestrian safety training in a smartphone-based virtual reality (VR) environment is not inferior to training in a large, semi-immersive VR environment with demonstrated effectiveness. METHODS: Five hundred 7- and 8-year-old children participated; 479 were randomized to one of two conditions: Learning to cross streets in a smartphone-based VR or learning in a semi-immersive kiosk VR. The systems used identical virtual environments and scenarios. At baseline, children's pedestrian skills were assessed in both VR systems and through a vehicle approach estimation task (judging speed/distance of oncoming traffic on monitor). Training in both conditions comprised at least six 30-min sessions in the randomly assigned VR platform and continued for up to 25 visits until adult-level proficiency was obtained. Following training and again 6 months later, children completed pedestrian safety assessments identical to baseline. Three outcomes were considered from assessments in each VR platform: Unsafe crossings (collisions plus close calls), time to contact (shortest time between child and oncoming simulated traffic), and missed opportunities (unselected safe opportunities to cross). RESULTS: Participants achieved adult-level street-crossing skill through VR training. Training in a smartphone-based VR system was generally not inferior to training in a large semi-immersive VR system. There were no adverse effects. CONCLUSIONS: Seven- and 8-year-old children can learn pedestrian safety through VR-based training, including training in a smartphone-based VR system. Combined with recent meta-analytic results, the present findings support broad implementation and dissemination of child pedestrian safety training through VR, including smartphone-based VR systems.