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.

A systematic review of lethal means safety counseling interventions: impacts on safety behaviors and self-directed violence.

For lethal means safety counseling (LMSC) interventions to reduce population-level suicide rates, interventions must be deployed across many settings and populations. We conducted a systematic search in 6 databases to review the current state of LMSC interventions across study designs, settings, intervention providers, populations, and injury prevention levels (eg, universal). Eligibility criteria were as follows: any individual or group receiving an LMSC intervention involving a human-to-human component aiming to influence adult behaviors related to lethal suicide methods, and outcome assessment of storage behaviors and/or suicidal self-directed violence (SDV). Risk of bias was assessed using the Effective Public Health Practice Project quality assessment tool. A descriptive synthesis approach was used for analysis. Twenty-two studies were included that reported medication- and/or firearm-storage behaviors and/or SDV after LMSC. Of the 19 studies assessing behavioral change, 14 reported a significant improvement in safe storage behaviors, and all studies measuring acceptability reported that participants found the interventions favorable. The quality of evidence was limited. No studies were rated low risk of bias, and 77% were rated high risk of bias. There was substantial heterogeneity in the settings, populations, injury prevention levels, delivery methods, and intervention elements. Many included studies focused on caregivers of pediatric populations, and few studies assessed SDV outcomes. Higher-quality trials conducted across a variety of settings, particularly those focusing on adults at risk of suicide, are needed. This review was preregistered with the International Prospective Register of Systematic Reviews (no. CRD42021230668).

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.

Behaviour of motorcyclists and bicyclists before and after a road safety campaign, China.

Objective: To examine changes in red-light running and distracted riding among motorcyclists and cyclists before and after the 2020 implementation of the One Helmet, One Seatbelt campaign in China. Methods: We obtained 192 hours of film before (2019) and after (2021) implementation of the campaign in eight road intersections in Changsha. We calculated percentages and ratios of red-light running and distracted riding. To assess the associations between these traffic behaviours and the campaign, we used multivariable logistic regression models to calculate adjusted odds ratios (aOR). Findings: We filmed 5256 motorcyclists and cyclists in 2019 and 6269 in 2021. Red-light running decreased from 45.1% to 41.5% during this period (ratio: 0.92; 95% confidence interval, CI: 0.88-0.96), while distracted riding increased from 3.5% to 5.0% (ratio: 1.42; 95% CI: 1.19-1.69). After adjusting for covariates, male riders were more likely to run a red light compared to female riders (aOR: 1.28; 95% CI: 1.06-1.55). Red-light running was also more likely among electric bicycle riders (aOR: 1.46; 95% CI: 1.10-1.95) and motorcyclists (aOR: 1.47; 95% CI: 1.13-1.90) compared to traditional cyclists. All types of riders were less prone to run a red light during peak hours than off-peak hours (aOR: 0.85; 95% CI: 0.73-0.99). Distracted riding was more common on weekends compared to weekdays (aOR: 3.01; 95% CI: 2.02-4.49). Conclusion: China's national road safety campaign, which focuses on helmet and seatbelt use, was associated with reduced red-light running. Strict enforcement and targeted modifications could improve the campaign's effectiveness.

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.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.

Efficiency of succinylated gelatin and amino acid infusions for kidney uptake reduction of radiolabeled αvß6-integrin targeting peptides: considerations on clinical safety profiles.

PURPOSE: 68Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvß6-integrin for PET imaging of carcinomas. 177Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact of different kidney protection strategies on the biodistribution of both agents in normal and tumor-bearing mice. METHODS: Ex-vivo biodistribution of 68Ga-Trivehexin (90 min p.i.) and 177Lu-D0301 (90 min and 24 h p.i.) was determined in healthy C57BL/6N and H2009 (human lung adenocarcinoma) xenografted CB17-SCID mice without and with co-infusion of 100 µL of solutions containing 2.5% arginine + 2.5% lysine (Arg/Lys), 4% succinylated gelatin (gelofusine, gelo), or combinations thereof. Arg/Lys was injected either i.p. 30 min before and after the radiopharmaceutical, or i.v. 2 min before the radiopharmaceutical. Gelo was administered either i.v. 2 min prior activity, or pre-mixed and injected together with the radiopharmaceutical (n = 5 per group). C57BL/6N mice were furthermore imaged by PET (90 min p.i.) and SPECT (24 h p.i.). RESULTS: Kidney uptake of 68Ga-Trivehexin in C57BL/6N mice was reduced by 15% (Arg/Lys i.p.), 25% (Arg/Lys i.v.), and 70% (gelo i.v.), 90 min p.i., relative to control. 177Lu-D0301 kidney uptake was reduced by 2% (Arg/Lys i.p.), 41% (Arg/Lys i.v.), 61% (gelo i.v.) and 66% (gelo + Arg/Lys i.v.) 24 h p.i., compared to control. Combination of Arg/Lys and gelo provided no substantial benefit. Gelo furthermore reduced kidney uptake of 177Lu-D0301 by 76% (90 min p.i.) and 85% (24 h p.i.) in H2009 bearing SCID mice. Since tumor uptake was not (90 min p.i.) or only slightly reduced (15%, 24 h p.i.), the tumor/kidney ratio was improved by factors of 3.3 (90 min p.i.) and 2.6 (24 h p.i.). Reduction of kidney uptake was demonstrated by SPECT, which also showed that the remaining activity was located in the cortex. CONCLUSIONS: The kidney uptake of both investigated radiopharmaceuticals was more efficiently reduced by gelofusine (61-85%) than Arg/Lys (25-41%). Gelofusine appears particularly suitable for reducing renal uptake of αvß6-integrin targeted 177Lu-labeled peptide multimers because its application led to approximately three times higher tumor-to-kidney ratios. Since the incidence of severe adverse events (anaphylaxis) with succinylated gelatin products (reportedly 0.0062-0.038%) is comparable to that of gadolinium-based MRI or iodinated CT contrast agents (0.008% and 0.04%, respectively), clinical use of gelofusine during radioligand therapy appears feasible if similar risk management strategies as for contrast agents are applied.

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.

Objective Neighborhood-Level Disorder Versus Subjective Safety as Predictors of HIV Transmission Risk and Momentary Well-Being.

Mental health and HIV risk behavior have been studied with ecological momentary assessment (EMA), but this approach has not been combined with tracking of activity space (where people go and what they encounter there) in people with HIV and their social relations, who may be HIV+ or HIV-. Activity space represents a modifiable risk or protective factor for behavior related to health status and quality of life, in both clinical and nonclinical populations. We conducted an observational study with 286 participants (243 HIV+ and 43 HIV-), roughly matched for socioeconomic status and neighborhood of residence via three waves of snowball sampling. Each participant carried a smartphone for up to 4 weeks, making 5 randomly prompted entries and 1 end-of-day entry each day, plus self-initiated event-contingent entries for sexual activity and drug use. Responses to randomly prompted items provided subjective evaluations of the safety of the participant's current social and physical environment (the place they were and the people they were with). GPS-based location tracking-coupled with publicly available statistic indicating neighborhood-level physical disorder and socioeconomic disadvantage-provided an indicator of each participant's exposure to objective psychosocial hazard. We examined possible relationships of these objective and subjective environmental exposures with risky sexual and intravenous drug-use behavior, knowledge and utilization of antiretroviral treatment and prophylaxis, and momentary mental health (mood and stress, which relate to risky behavior and overall well-being). We found that both risky behavior and mental health were more related to participants' subjective evaluations of their activity space than to objective measures of neighborhood-level disorder, suggesting that, even within an objectively hazardous neighborhood, people who find a niche they perceive as socially and physically safe may engage in less risky behavior and have better well-being.Trial registration Clinicaltrials.gov Identifier NCT01571752.

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 Concerns and the Onset of Depressive Symptoms Among Women: A Population-based Prospective Cohort Study in South Korea.

Neighborhood safety is crucial for the well-being of residents; however, longitudinal evidence is scarce. This study explored the association between neighborhood safety concerns and depressive symptoms among women. A nationally representative sample of 10,008 women was surveyed in 2016. Six dimensions of neighborhood safety concerns were assessed: crime, food, safety at night, traffic accidents, building and facility, and general safety. The total score for neighborhood safety concerns ranged from 6 to 24, with higher scores indicating greater concerns. Depressive symptoms were assessed using the 10-item version of the Center for Epidemiologic Studies Depression. For cross-sectional analyses, we explored how neighborhood safety concerns were associated with concurrent depressive symptoms at baseline. For the longitudinal analyses, we explored how they were associated with depressive symptom onset at the 2-year follow-up (2018) among women without depressive symptoms at baseline (n = 7,643). Logistic regressions were employed. The mean (standard deviation [SD]) of the neighborhood safety concern score was 12.7 (3.3). In the cross-sectional analysis, a 1-SD increase in neighborhood safety concern score was associated with 1.23-fold (95% CI: 1.13-1.35) increase in the odds of concurrent depressive symptoms at the baseline year. In the longitudinal analysis, a 1-SD increase in neighborhood safety concern score was associated with 1.15-fold (95% CI: 1.03-1.29) increase in the odds of experiencing the onset of depressive symptoms at the follow-up year. This study suggests that neighborhood safety concerns are risk factors for the development of depressive symptoms of female residents. Policy efforts are necessary to ensure community safety.