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Current views of O 2 accumulation in Earth history depict three phases: The onset of O 2 production by ∼2.4 billion years ago; 2 billion years of stasis at ∼1 % of modern atmospheric levels; and a rising phase, starting about 500 million years ago, in which oxygen eventually reached modern values. Purely geochemical mechanisms have been proposed to account for this tripartite time course of Earth oxygenation. In particular the second phase, the long period of stasis between the advent of O 2 and the late rise to modern levels, has posed a puzzle. Proposed solutions involve Earth processes (geochemical, ecosystem, day length). Here we suggest that Earth oxygenation was not determined by geochemical processes. Rather it resulted from emergent biological innovations associated with photosynthesis and the activity of only three enzymes: 1) The oxygen evolving complex of cyanobacteria that makes O 2 ; 2) Nitrogenase, with its inhibition by O 2 causing two billion years of oxygen level stasis; 3) Cellulose synthase of land plants, which caused mass deposition and burial of carbon, thus removing an oxygen sink and therefore increasing atmospheric O 2 . These three enzymes are endogenously produced by, and contained within, cells that have the capacity for exponential growth. The catalytic properties of these three enzymes paved the path of Earth's atmospheric oxygenation, requiring no help from Earth other than the provision of water, CO 2 , salts, colonizable habitats, and sunlight., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Globally, Mexico is one of six countries with the highest level of firearm mortality. While previous studies have examined firearm mortality in Mexico before 2015, increases in violence since then highlight the need for an updated analysis. In this study, we examined changes in firearm-related deaths in Mexico from 2015 to 2022 and described these deaths by key demographic groups, incident location, and state of occurrence. Data came from Mexico's Instituto Nacional de Estadistica y Geografia (INEGI), a federal agency that collects and reports national population data. We used descriptive statistics to analyze rates, proportions, and percentage changes in firearm mortality, and we displayed temporal trends using time plots and special trends using maps., Results: Firearm deaths increased in Mexico from 2015 to 2018 but slightly decreased from 2018 to 2022. Homicides presented the highest increase and the highest proportion of firearm-related deaths from 2015 to 2022. Victims were primarily males but rates among women increased at a higher proportion (99.5% vs 53.5%). One third of victims were 20-29y but rates among children and adolescents (10-9y) increased at a higher proportion. Most firearm-related deaths occurred in streets or public spaces but the percentage of incidents occurring in households have increased. State-level rates and percentage changes varied significantly. States with higher rates of firearm mortality coincide with those involving conflict among organized criminal organizations., Conclusion: Firearm mortality in Mexico is a major public health burden. The epidemiology of firearm-related deaths in Mexico varies by intent, demographics, location, and states. To mitigate this challenge, multiple solutions are required., (© 2024. The Author(s).)

The formation of congestion on an urban road network is a key issue for the development of sustainable mobility in future smart cities. In this work, we propose a reductionist approach by studying the stationary states of a simple transport model using a random process on a graph, where each node represents a location and the link weights give the transition rates to move from one node to another, representing the mobility demand. Each node has a maximum flow rate and a maximum load capacity, and we assume that the average incoming flow equals the outgoing flow. In the approximation of the single-step process, we are able to analytically characterize the traffic load distribution on the single nodes using a local maximum entropy principle. Our results explain how congested nodes emerge as the total traffic load increases, analogous to a percolation transition where the appearance of a congested node is an independent random event. However, using numerical simulations, we show that in the more realistic case of synchronous dynamics for the nodes, entropic forces introduce correlations among the node states and favor the clustering of empty and congested nodes. Our aim is to highlight the universal properties of congestion formation and, in particular, to understand the role of traffic load fluctuations as a possible precursor of congestion in a transport network.

Objective: This study aims to characterise the motivations of firearm owners and examine whether firearm ownership motivations and carriage varied by state stand your ground law status.  METHODS: Using a nationally representative survey of US adults in 2023, we asked firearm owners (n=2477) about their firearm motivations and behaviours, including reason(s) for ownership., Results: Of all firearm owners, 78.8% (95% CI 76.0% to 81.0%) owned a firearm for protection, and 58.1% (95% CI 54.3% to 62.0%) carried a firearm outside their home in the last 12 months. Firearm ownership for protection was not significantly associated with stand your ground laws, but firearm carriage was more prevalent in states with stand your ground laws (50.1% (95% CI 47.0% to 53.0%) vs 34.9% (95% CI 25.0% to 46.0%)). Gender (women) and race (minority groups) emerged as key correlates for firearm ownership for protection (vs other ownership motivations). For example, black and Asian women (98.8%) almost exclusively owned firearms for protection., Conclusions: Protection was the dominant reason for firearm ownership in 2023, motivating 65 million Americans to own firearms and appealing to different strata of the population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Sexual assault among higher education students has detrimental impacts on the health and educational outcomes of survivors. This systematic review aims to describe and synthesize the available quantitative evidence on sexual assault prevalence among this population. We searched Medline, EMBASE, Global Health, PsycINFO, Web of Science, ERIC, and CINAHL for studies published in English, French, Italian, and Spanish from database inception to August 2020 (updated May 2022). We screened studies using prespecified inclusion criteria for the population and context (registered higher education students), condition (self-reported sexual assault), and study design (quantitative survey). The Joanna Briggs Institute Critical Appraisal Checklist was used to assess study quality. Prevalence estimates disaggregated by type of sexual assault, gender identity, and world region were meta-analyzed using a random-effects model and reported following PRISMA guidance. We identified 131 articles, from 21 different countries. The meta-analyzed prevalence of sexual assault was 17.5% for women, 7.8% for men, and 18.1% for transgender and gender diverse people. Four types of sexual assault were identified: rape, attempted rape, forced sexual touching, and coercive sex. Forced sexual touching was the most common act experienced. The African Region had the highest prevalence estimates for women's sexual assault, and the Western Pacific region had the highest prevalence estimates for men's sexual assault. Higher education institutions, especially those outside of the United States, should commit to the implementation of surveys to monitor sexual assault prevalence and dedicate increased resources to supporting student survivors of sexual assault., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Homicide is the leading cause of death among young people in Latin America, one of the world's most violent regions. Poverty is widely considered a key cause of violence, but theories suggest different effects of poverty, depending on when it is experienced in the life-course. Longitudinal studies of violence are scarce in Latin America, and very few prospective data are available worldwide to test different life-course influences on homicide., Methods: In a prospective birth cohort study following 5914 children born in southern Brazil, we examined the role of poverty at birth, in early childhood, and in early adulthood on violence and homicide perpetration, in criminal records up to age 30 years. A novel Structured Life Course Modelling Approach was used to test competing life-course hypotheses about 'sensitive periods', 'accumulation of risk', and 'downward mobility' regarding the influence of poverty on violence and homicide., Results: Cumulative poverty and poverty in early adulthood were the most important influences on violence and homicide perpetration. This supports the hypothesis that early adulthood is a sensitive period for the influence of poverty on lethal and non-lethal violence. Results were replicable using different definitions of poverty and an alternative outcome of self-reported fights., Conclusion: Cumulative poverty from childhood to adulthood was an important driver of violence and homicide in this population. However, poverty experienced in early adulthood was especially influential, suggesting the importance of proximal mechanisms for violence in this context, such as unemployment, organized crime, drug trafficking, and ineffective policing and justice systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Mitophagy is the process of selective autophagy that removes superfluous and dysfunctional mitochondria. Mitophagy was first characterized in mammalian cells and is now recognized to follow several pathways including basal forms in specific organs. Mitophagy pathways are regulated by multiple, often interconnected factors. The present review aims to streamline this complexity and evaluate common elements that may define the evolutionary origin of mitophagy. Key issues surrounding mitophagy signaling at the mitochondrial surface may fundamentally derive from mitochondrial membrane dynamics. Elements of such membrane dynamics likely originated during the endosymbiosis of the alphaproteobacterial ancestor of our mitochondria but underwent an evolutionary leap forward in basal metazoa that determined the currently known variations in mitophagy signaling. Abbreviations : AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; ATG, autophagy related; BCL2L13, BCL2 like 13; BNIP3, BCL2 interacting protein 3; BNIP3L, BCL2 interacting protein 3 like; CALCOCO, calcium binding and coiled-coil domain; CL, cardiolipin; ER, endoplasmic reticulum; ERMES, ER-mitochondria encounter structure; FBXL4, F-box and leucine rich repeat protein 4; FUNDC1, FUN14 domain containing 1; GABARAPL1, GABA type A receptor associated protein like 1; HIF, hypoxia inducible factor; IMM, inner mitochondrial membrane; LBPA/BMP, lysobisphosphatidic acid; LIR, LC3-interacting region; LPA, lysophosphatidic acid; MAM, mitochondria-associated membranes; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MCL, monolysocardiolipin; ML, maximum likelihood; NBR1, NBR1 autophagy cargo receptor; OMM, outer mitochondrial membrane; PA, phosphatidic acid; PACS2, phosphofurin acidic cluster sorting protein 2; PC/PLC, phosphatidylcholine; PE, phosphatidylethanolamine; PHB2, prohibitin 2; PINK1, PTEN induced kinase 1; PtdIns, phosphatidylinositol; SAR, Stramenopiles, Apicomplexa and Rhizaria; TAX1BP1, Tax1 binding protein 1; ULK1, unc-51 like autophagy activating kinase 1; VDAC/porin, voltage dependent anion channel.

Sexual violence (SV) experienced by higher education students is a prevalent public health problem. Collecting data on SV through self-report surveys in higher education institutions (HEIs) is essential for estimating the scope of the problem, the first step to adequately resourcing and implementing prevention and response programming and policies. However, in the United Kingdom, data is limited. We used data from the cross-sectional Oxford Understanding Relationships, Sex, Power, Abuse and Consent Experiences survey, administered to all students at a university in the United Kingdom in May 2021 ( n  = 25,820), to estimate the past year prevalence of SV. We analyzed data from respondents who answered at least one question on SV ( n  = 1,318) and found that 20.5% of respondents experienced at least one act of attempted or forced sexual touching or rape, and 52.7% of respondents experienced at least one act of sexual harassment (SH). We found that women experienced the highest rates of SV. Attempted forced sexual touching was far more common than forced sexual touching, or rape. Sexist remarks or jokes were the most common act of SH. Most acts of SV took place at the university. These findings reveal that the prevalence of SV in HEIs in the United Kingdom could be far higher than what is experienced in the general population. While this study reflects the context in only one institution, it underlines the need for continued monitoring to develop rigorous, evidence-based, and targeted prevention and response strategies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Adult social care services in England are struggling, and sometimes failing, to supply the quality of care deserved by the most vulnerable people in society. The Care Quality Commission (CQC) is responsible for protecting the recipients of this crucial public service. Their strongest enforcement is the ability to cancel the registration-the legal right to operate-of a health or social care provider. Using novel data from the CQC, we show that the proportion of care home closures due to CQC enforcements, relative to all closures, is increasing. Since 2011, 816 care homes (representing 19 918 registered beds) have been involuntarily closed by the CQC. Our results show that effectively all involuntary closures (804/816) occurred in for-profit care homes. This data emphasises the need for a comprehensive assessment of the impact of for-profit provision on the quality and sustainability of adult social care in England., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Adolescence is a key developmental window that may determine long-term mental health. As schools may influence mental health of students, this study aimed to examine the association of school-level characteristics with students' mental health over time., Method: Longitudinal data from a cluster randomized controlled trial comprising 8,376 students (55% female; aged 11-14 years at baseline) across 84 schools in the United Kingdom were analyzed. Data collection started in the academic years 2016/2017 (cohort 1) and 2017/2018 (cohort 2), with follow-up at 1, 1.5, and 2 years. Students' mental health (risk for depression [Center for Epidemiologic Studies Depression Scale], social-emotional-behavioral difficulties [Strength and Difficulties Questionnaire]) and well-being (Warwick-Edinburgh Mental Well-Being Scale) and relationships with student- and school-level characteristics were explored using multilevel regression models., Results: Mental health difficulties and poorer well-being increased over time, particularly in girls. Differences among schools represented a small but statistically significant proportion of variation (95% CI) in students' mental health at each time point: depression, 1.7% (0.9%-2.5%) to 2.5% (1.6%-3.4%); social-emotional-behavioral difficulties, 1.9% (1.1%-2.7%) to 2.8% (2.1%-3.5%); and well-being, 1.8% (0.9%-2.7%) to 2.2% (1.4%-3.0%). Better student-rated school climate analyzed as a time-varying factor at the student and school level was associated with lower risk of depression (regression coefficient [95%CI] student level: -4.25 [-4.48, -4.01]; school level: -4.28 [-5.81, -2.75]), fewer social-emotional-behavioral difficulties (student level: -2.46 [-2.57, -2.35]; school level: -2.36 [-3.08, -1.63]), and higher well-being (student level: 3.88 [3.70, 4.05]; school-level: 4.28 [3.17, 5.38]), which was a stable relationship., Conclusion: Student-rated school climate predicted mental health in early adolescence. Policy and system interventions that focus on school climate may promote students' mental health., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: To investigate differences in homicide and suicide rates across college town status and determine whether college towns were predisposed to changes in rates over time., Methods: We analyzed county-level homicide and suicide rates (total and by firearm) across college town status using 2015-2019 CDC death certificate data and data from the American Communities Project., Results: Population-level homicide rates were similar across college town status, but younger age groups were at increased risk for firearm homicide and total homicide in college towns. College town status was associated with lower population-level firearm suicide rates, but individuals aged less than 18 y were at increased risk for total and firearm suicide. Finally, college towns were not classified as outliers for changes in either firearm homicide or suicide rates over time., Conclusions: College towns had similar homicide rates and significantly lower firearm suicide rates than other counties; however, individuals aged less than 18 y were at increased risk for both outcomes. The distinctive demographic, social, economic, and cultural features of college towns may contribute to differing risk profiles among certain age groups, thus may also be amenable to focused prevention efforts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Acetobacteraceae are one of the best known and most extensively studied groups of bacteria, which nowadays encompasses a variety of taxa that are very different from the vinegar-producing species defining the family. Our paper presents the most detailed phylogeny of all current taxa classified as Acetobacteraceae , for which we propose a taxonomic revision. Several of such taxa inhabit some of the most extreme environments on the planet, from the deserts of Antarctica to the Sinai desert, as well as acidic niches in volcanic sites like the one we have been studying in Patagonia. Our work documents the progressive variation of the respiratory chain in early branching Acetobacteraceae into the different respiratory chains of acidophilic taxa such as Acidocella and acetous taxa such as Acetobacter . Remarkably, several genomes retain remnants of ancestral photosynthetic traits and functional bc 1 complexes. Thus, we propose that the common ancestor of Acetobacteraceae was photosynthetic., Competing Interests: The authors declare no conflict of interest.

Introduction: Despite promising reductions in mortality from infectious diseases, premature death is a still major public health problem in Brazil. However, little is known about which diseases and injury mechanisms are the main causes of premature death. This paper aimed to detail the trends in leading causes of death among children and adolescents in Brazil., Methods: Data were extracted from medical death certificates from the Brazilian Mortality Information System for children and adolescents aged 1-19 years for 2000-2020. The 10 leading causes of death for children and adolescents were defined using primary cause of death codes, grouped by death for diseases and mechanism for injury, according to the ICD-10. All analyses were completed in 2022., Results: From 2000 through 2020, there was a total of 772,729 child and adolescent deaths in Brazil. Despite an overall 34% reduction in child and adolescent mortality from 2000 to 2020, improvements were less pronounced for injury-related deaths than for communicable diseases. Therefore, by 2020, over half of deaths were from injury-related causes. Firearm-related injury was by far the leading cause, accounting for 21% of all deaths. There was a 38% reduction in firearm deaths in the last 4 years against a previously increasing trend, and homicide accounted for over 90% of all firearm deaths because suicide by firearm was rare., Conclusions: Injury-related deaths among children and adolescents are a growing concern in Brazil, and firearms are the current leading cause of child and adolescent death., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

We breathe at the molecular level when mitochondria in our cells consume oxygen to extract energy from nutrients. Mitochondria are characteristic cellular organelles that derive from aerobic bacteria and carry out oxidative phosphorylation and other key metabolic pathways in eukaryotic cells. The precise bacterial origin of mitochondria and, consequently, the ancestry of the aerobic metabolism of our cells remain controversial despite the vast genomic information that is now available. Here, we use multiple approaches to define the most likely living relatives of the ancestral bacteria from which mitochondria originated. These bacteria live in marine environments and exhibit the highest frequency of aerobic traits and genes for the metabolism of fundamental lipids that are present in the membranes of eukaryotes, sphingolipids, and cardiolipin.

Fully biobased and biodegradable materials have attracted a growing interest in the food packaging sector as they can help to reduce the negative impact of fossil-based plastics on the environment. Moreover, the addition of functionalities to these materials by introducing active molecules has become an essential requirement to create modern packaging able to extend food's shelf-life while informing the consumer about food quality and freshness. In this study, we present an innovative bioplastic formulation for food packaging based on poly(hydroxybutyrate- co -valerate) (PHBV) and tannins as multifunctional additives. As a proof of concept, PHBV/tannin films were prepared by solvent casting, increasing the tannin content from 1 to 10 per hundred of resin (phr). Formic acid was used to reach a homogeneous distribution of the hydrophilic tannins into hydrophobic PHBV, which is remarkably challenging by using other solvents. Thanks to their well-known properties, the effect of tannins on the antioxidant, UV protection, and gas barrier properties of PHBV was evaluated. Samples containing 5 phr bioadditive revealed the best combination of these properties, also maintaining good transparency. Differential scanning calorimetry (DSC) investigations revealed that films are suitable for application from the fridge to potentially high temperatures for food heating (up to 200 °C). Tensile tests have also shown that Young's modulus (900-1030 MPa) and tensile strength (20 MPa) are comparable with those of the common polymers and biopolymers for packaging. Besides the improvement of the PHBV properties for extending food's shelf-life, it was also observed that PHBV/tannin could colorimetrically detect ammonia vapors, thus making this material potentially applicable as a smart indicator for food spoilage (e.g., detection of fish degradation). The presented outcomes suggest that tannins can add multifunctional properties to a polymeric material, opening up a new strategy to obtain an attractive alternative to petroleum-based plastics for smart food packaging applications.

In the last two decades, the use of phthalates has been restricted worldwide due to their well-known toxicity. Nonetheless, phthalates are still widely used for their versatility, high plasticization effect, low cost, and lack of valuable alternatives. This study presents the fully bio-based and versatile glycerol trilevulinate plasticizer (GT) that was obtained by the valorization of glycerol and levulinic acid. The mild-conditions and solvent-free esterification used to synthesize GT was optimized by investigating the product by Fourier transform infrared and NMR spectroscopy. An increasing content of GT, from 10 to 40 parts by weight per hundred parts of resin (phr), was tested with poly(vinyl chloride), poly(3-hydroxybutyrate), poly(3-hydroxybutyrate- co -3-hydroxyvalerate), poly(lactic acid), and poly(caprolactone), which typically present complicated processability and/or mechanical properties. GT produced a significant plasticization effect on both amorphous and semicrystalline polymers, reducing their glass-transition temperature and stiffness, as observed by differential scanning calorimetry measurements and tensile tests. Remarkably, GT also decreased both the melting temperature and crystallinity degree of semicrystalline polymers. Furthermore, GT underwent enzyme-mediated hydrolysis to its initial constituents, envisioning a promising prospective for environmental safety and upcycling. Furthermore, 50% inhibitory concentration (IC 50 ) tests, using mouse embryo fibroblasts, proved that GT is an unharmful alternative plasticizer, which makes it potentially applicable in the biomedical field., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aims: Previous epidemiological evidence identified a concerning increase in behavioural problems among young children from 1997 to 2008 in Brazil. However, it is unclear whether behavioural problems have continued to increase, if secular changes vary between sociodemographic groups and what might explain changes over time. We aimed to monitor changes in child behavioural problems over a 22-year period from 1997 to 2019, examine changing social inequalities and explore potential explanations for recent changes in behavioural problems between 2008 and 2019., Methods: The Child Behaviour Checklist was used to compare parent-reported behavioural problems in 4-year-old children across three Brazilian birth cohorts assessed in 1997 (1993 cohort, n  = 633), 2008 (2004 cohort, n  = 3750) and 2019 (2015 cohort, n  = 577). Response rates across all three population-based cohorts were over 90%. Moderation analyses tested if cross-cohort changes differed by social inequalities (demographic and socioeconomic position), while explanatory models explored whether changes in hypothesized risk and protective factors in prenatal development (e.g., smoking during pregnancy) and family life (e.g., maternal depression and harsh parenting) accounted for changes in child behavioural problems from 2008 to 2019., Results: Initial increases in child behavioural problems from 1997 to 2008 were followed by declines in conduct problems (mean change = -2.75; 95% confidence interval [CI]: -3.56, -1.94; P  < 0.001), aggression (mean change = -1.84; 95% CI: -2.51, -1.17; P  < 0.001) and rule-breaking behaviour (mean change = -0.91; 95% CI: -1.13, -0.69 P  < 0.001) from 2008 to 2019. Sex differences in rule-breaking behaviour diminished during this 22-year period, whereas socioeconomic inequalities in behavioural problems emerged in 2008 and then remained relatively stable. Consequently, children from poorer and less educated families had higher behavioural problems, compared to more socially advantaged children, in the two more recent cohorts. Changes in measured risk and protective factors partly explained the reduction in behavioural problems from 2008 to 2019., Conclusions: Following a rise in child behavioural problems, there was a subsequent reduction in behavioural problems from 2008 to 2019. However, social inequalities increased and remained high. Continued monitoring of behavioural problems by subgroups is critical for closing the gap between socially advantaged and disadvantaged children and achieving health equity for the next generation.

A significant mechanical properties mismatch between natural bone and the material forming the orthopedic implant device can lead to its failure due to the inhomogeneous loads distribution, resulting in less dense and more fragile bone tissue (known as the stress shielding effect). The addition of nanofibrillated cellulose (NFC) to biocompatible and bioresorbable poly(3-hydroxybutyrate) (PHB) is proposed in order to tailor the PHB mechanical properties to different bone types. Specifically, the proposed approach offers an effective strategy to develop a supporting material, suitable for bone tissue regeneration, where stiffness, mechanical strength, hardness, and impact resistance can be tuned. The desired homogeneous blend formation and fine-tuning of PHB mechanical properties have been achieved thanks to the specific design and synthesis of a PHB/PEG diblock copolymer that is able to compatibilize the two compounds. Moreover, the typical high hydrophobicity of PHB is significantly reduced when NFC is added in presence of the developed diblock copolymer, thus creating a potential cue for supporting bone tissue growth. Hence, the presented outcomes contribute to the medical community development by translating the research results into clinical practice for designing bio-based materials for prosthetic devices.

Background: City-led interventions are increasingly advocated to achieve the UN's Sustainable Development Goal to reduce violence for all. We used a new quantitative evaluation method to examine whether a flagship programme, called the "Pelotas Pact for Peace" (the Pacto), has been effective in reducing violence and crime in the city of Pelotas, Brazil., Methods: We used synthetic control methodology to assess the effects of the Pacto from August 2017 to December 2021, and separately before and during the COVID-19 pandemic. Outcomes included monthly rates of homicide and property crime, and yearly rates of assault against women and school drop-out. We constructed synthetic controls (counterfactuals) based on weighted averages from a donor pool of municipalities in Rio Grande do Sul. Weights were identified using pre-intervention outcome trends and confounders (sociodemographics, economics, education, health and development, and drug trafficking)., Findings: The Pacto led to an overall 9% reduction in homicide and 7% reduction in robbery in Pelotas. These effects were not uniform across the full post-intervention period as clear effects were only seen during the pandemic period. A 38% reduction in homicide was also specifically associated with the criminal justice strategy of Focussed Deterrence. No significant effects were found for non-violent property crimes, violence against women, and school dropout, irrespective of the post-intervention period., Interpretation: City-level interventions that combine public health and criminal justice approaches could be effective in tackling violence in Brazil. Continued monitoring and evaluation efforts are increasingly needed as cities are proposed as key opportunities for reducing violence for all., Funding: This research was funded by the Wellcome Trust [grant number: 210735&#95;Z&#95;18&#95;Z]., Competing Interests: JM collaborated with the Municipal Government of Pelotas on one project included in the Pelotas Peace Pact. That was a randomised trial of two of the early childhood parenting interventions, as documented in Murray et al. (2019),43 and the municipal government contributed funds to conduct the trial. All other authors declare no competing interests., (© 2023 The Authors.)

Background: Firearm violence is one of the leading preventable causes of death and injury in the United States and is on the rise. While policies regulating access to firearms offer opportunities to prevent firearm-related deaths, an understanding of the holistic impact of changing state firearm policies on firearm homicide rates over the last 30 years is limited., Objectives: To identify US states that showed unexpected decreases and increases in firearm homicide rates and summarise their firearm policy changes in the last three decades., Methods: We analysed changes in firearm homicide rates by US state and county from 1990 to 2019. We triangulated across three estimation approaches to derive state rankings and identify the top and bottom three states which consistently showed unexpected decreases (low outliers) and increases (high outliers) in firearm homicide rates. We summarised firearm policy changes in state outliers using the RAND State Firearm Law Database., Results: We identified New York, District of Columbia, and Hawaii as low state outliers and Delaware, New Jersey, and Missouri as high state outliers. Low state outliers made more restrictive firearm policy changes than high state outliers, which covered a wider range of policy types. Restrictive changes in high state outliers primarily targeted high-risk populations (e.g., prohibited possessors, safe storage). Specific legislative details, such as the age threshold (18 vs 21 years old) for firearm minimum age requirements, also emerged as important for differentiating low from high state outliers., Conclusions: While no firearm law change emerged as necessary or sufficient, an accumulation of diverse restrictive firearm policies may be key to alleviating the death toll from firearm homicide., Competing Interests: None., (© 2023 The Authors.)

The effect of polyhydroxyalkanoates (PHAs) with different composition on the reductive dechlorination activity of a polychlorinated biphenyls (PCBs) dechlorinating marine microbial community and on the activity of sulfate-reducing (SRB) and methanogenic bacteria (MB), were investigated in marine sediment microcosms and compared with the main monomer, 3-hydroxybutyric acid (3HB). Despite PHAs were fermented more slowly than 3HB, all electron donors stimulated constantly sulfate-reduction, methanogenesis and, only transiently, PCB reductive dechlorination. No relevant differences were observed with different compositions of PHAs. According to electron balances, the majority of the supplied electrons (50 %) were consumed by SRB and to less extent by MB (9-31 %), while a small percentage (0.01 %) was delivered to OHRB. In the studied conditions PHAs were confirmed as potential slow‑hydrogen releasing compounds in marine environment but their fermentation rate was sufficiently high to mainly stimulate the competitors of organohalide respring bacteria for electron donors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This article provides an updated review on the evolution of mitochondria from bacteria, which were likely related to extant alphaproteobacteria. Particular attention is given to the timeline of oxygen history on Earth and the entwined phases of eukaryotic evolution that produced the animals that still populate our planet. Mitochondria of early-branching unicellular eukaryotes and plants appear to retain partial or vestigial traits that were directly inherited from the alphaproteobacterial ancestors of the organelles. Most of such traits define the current aerobic physiology of mitochondria. Conversely, the anaerobic traits that would be essential in the syntrophic associations postulated for the evolution of eukaryotic cells are scantly present in extant alphaproteobacteria, and therefore cannot help defining from which bacterial lineage the ancestors of mitochondria originated. This question has recently been addressed quantitatively, reaching the novel conclusion that marine bacteria related to Iodidimonas may be the living relatives of protomitochondria. Additional evidence is presented that either support or does not contrast this novel view of the bacterial origin of mitochondria., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Firearm violence remains a critical public health challenge, disproportionately impacting some US regions. County-level variation may hold key insights into how firearm mortality rates vary across the US., Objective: To model county-level changes in firearm mortality rates (total, homicide, and suicide) from 1989 to 1993 vs 2015 to 2019 and identify and characterize hot spots showing unexpected changes over time., Design, Setting, and Participants: This is a cross-sectional study with 2 time points using a novel small area estimation method to analyze restricted access mortality microdata by cause of death and US county. The analysis included 3111 US counties from 49 states and the District of Columbia from January 1, 1989, to December 31, 2019. Bayesian spatial models were fitted to map geographical variation in changes in age-standardized firearm mortality rates (per 100 000 person-years) from 1989 to 1993 vs 2015 to 2019. County outliers (or hot spots) were defined as having observed rates that fell outside the 95% credible intervals of their expected posterior predictive distribution. These counties were characterized using visualization and descriptive statistics of their characteristics. Data were analyzed from June to December 2021., Exposures: County of residence., Main Outcomes and Measures: Five-year age-standardized mortality rates by US county, age, and cause of death for 1989 to 1993 and 2015 to 2019., Results: Between 1989 and 2019, 1 036 518 firearm deaths were recorded in counties across the US. Suicide was the most common cause of firearm mortality (589 285 deaths) followed by homicide (412 231 deaths). Age-standardized rates (deaths per 100 000 individuals) for firearm deaths and suicides increased from 1989 to 1993 vs 2015 to 2019 (mean [SD] change, 0.16 [8.78] for firearm deaths and 1.21 [6.91] for suicides), while firearm homicides decreased (mean [SD] change, -0.39 [3.96]). However, these national trends were not homogeneous across counties and often varied by geographical region. The West and Midwest showed the most pronounced increases in firearm suicide rates, whereas the Southeast showed localized increases in firearm homicide rates, despite the national decreasing trend. Critical hot spots were identified in urban counties of Alabama, and firearm homicide rates (per 100 000) in Baltimore City, Maryland, almost doubled from 29.71 to 47.43, and by 2015 to 2019 it accounted for 66.7% of all firearm homicide in Maryland. By contrast, District of Columbia showed promising improvements over time, decreasing from 56.5 firearm homicides per 100 000 in 1989 to 1993 to 14.45 in 2015 to 2019., Conclusions and Relevance: There was substantial variation in rates and changes in firearm deaths among US counties. Geographical hot spots may be useful to inform targeted prevention efforts and local policy responses.

Ocular graft versus host disease (GVHD) is a common manifestation in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). Ocular GVHD affects approximately 10% of patients with acute GVHD and more than 50% of patients with chronic GVHD. Symptoms of dry eye disease are one of the clinical hallmarks of ocular GVHD, and inflammatory changes to the ocular surface, cornea, conjunctiva, eyelids and lacrimal glands have been observed. Less commonly, the posterior segment of the eye is involved in the form of microvascular retinopathy, scleritis or intraretinal and vitreous haemorrhage. Although ocular GVHD does not usually result in permanent visual loss, it often impairs the patient's quality of life and activities of daily living. Regular and more consistent ocular assessment of allo-HSCT patients, including screening prior to transplantation will allow for the earlier detection and treatment of ocular complications associated with GVHD and potentially prevent more severe outcomes. The implementation of additional screening including corneal endothelial cell density assessment and non-invasive analysis of tear biomarkers may be valuable additions to current clinical testing and assist in better detection and clinical intervention in patients with GVHD. This review describes the clinical features, diagnostic criteria and clinical scoring of ocular GVHD, as well as current treatment strategies and potential ophthalmic screening tools for common ocular complications. Further, we describe the clinical and histopathological features of ocular GVHD in preclinical mouse models.

The finding that the most common mitochondrial DNA mutation m.11778G>A/ MT-ND4 (p.R340H) associated with Leber's hereditary optic neuropathy (LHON) induces rotenone resistance has produced a long-standing debate, because it contrasts structural evidence showing that the ND4 subunit is far away from the quinone-reaction site in complex I, where rotenone acts. However, recent cryo-electron microscopy data revealed that rotenone also binds to the ND4 subunit. We investigated the possible structural modifications induced by the LHON mutation and found that its amino acid replacement would disrupt a possible hydrogen bond between native R340 and Q139 in ND4, thereby destabilizing rotenone binding. Our analysis thus explains rotenone resistance in LHON patients as a biochemical signature of its pathogenic effect on complex I.

We survey here the Alphaproteobacteria, a large class encompassing physiologically diverse bacteria which are divided in several orders established since 2007. Currently, there is considerable uncertainty regarding the classification of an increasing number of marine metagenome-assembled genomes (MAGs) that remain poorly defined in their taxonomic position within Alphaproteobacteria. The traditional classification of NCBI taxonomy is increasingly complemented by the Genome Taxonomy Database (GTDB), but the two taxonomies differ considerably in the classification of several Alphaproteobacteria, especially from ocean metagenomes. We analyzed the classification of Alphaproteobacteria lineages that are most common in marine environments, using integrated approaches of phylogenomics and functional profiling of metabolic features that define their aerobic metabolism. Using protein markers such as NuoL, the largest membrane subunit of complex I, we have identified new clades of Alphaproteobacteria that are specific to marine niches with steep oxygen gradients (oxycline). These bacteria have relatives among MAGs found in anoxic strata of Lake Tanganyika and together define a lineage that is distinct from either Rhodospirillales or Sneathiellales. We characterized in particular the new 'oxycline' clade. Our analysis of Alphaproteobacteria also reveals new clues regarding the ancestry of mitochondria, which likely evolved in oxycline marine environments.

Importance: Most US states have amended self-defense laws to enhance legal immunities for individuals using deadly force in public. Despite concerns that "stand your ground" (SYG) laws unnecessarily encourage the use of deadly violence, their impact on violent deaths and how this varies across states and demographic groups remains unclear., Objective: To evaluate the association of SYG laws with homicide and firearm homicide, nationally and by state, while considering variation by the race, age, and sex of individuals who died by homicide., Design, Setting, and Participants: This cohort study used a controlled, multiple-baseline and -location interrupted time series design, using natural variation in the timings and locations of SYG laws to assess associations. Changes in homicide and firearm homicide were modeled using Poisson regression analyses within a generalized additive model framework. Analyses included all US states that enacted SYG laws between 2000 and 2016 and states that did not have SYG laws enacted during the full study period, 1999 to 2017. Data were analyzed from November 2019 to December 2020., Exposures: SYG self-defense laws enacted by statute between January 1, 2000, to December 31, 2016., Main Outcomes and Measures: The main outcomes were statewide monthly rates of homicide and firearm-related homicide (per 100 000 persons) from January 1, 1999, to December 31, 2017, grouped by characteristics (ie, race, age, sex) of individuals who died by homicide., Results: Forty-one states were analyzed, including 23 states that enacted SYG laws during the study period and 18 states that did not have SYG laws, with 248 358 homicides (43.7% individuals aged 20-34 years; 77.9% men and 22.1% women), including 170 659 firearm homicides. SYG laws were associated with a mean national increase of 7.8% in monthly homicide rates (incidence rate ratio [IRR],1.08; 95% CI, 1.04-1.12; P < .001) and 8.0% in monthly firearm homicide rates (IRR, 1.08; 95% CI, 1.03-1.13; P = .002). SYG laws were not associated with changes in the negative controls of suicide (IRR, 0.99; 95% CI, 0.98-1.01) or firearm suicide (IRR, 1.00; 95% CI, 0.98-1.02). Increases in violent deaths varied across states, with the largest increases (16.2% to 33.5%) clustering in the South (eg, Alabama, Florida, Georgia, Louisiana). There were no differential associations of SYG laws by demographic group., Conclusions and Relevance: These findings suggest that adoption of SYG laws across the US was associated with increases in violent deaths, deaths that could potentially have been avoided.

Torlon ® is a thermally and plasticization-resistant polyamide imide characterized by low gas permeability at room temperature. In this work, we aimed at improving the polymer performance in the thermally-enhanced He/CO 2 and H 2 /CO 2 separations, by compounding Torlon ® with a highly permeable filler, ZIF-8, to fabricate Mixed Matrix Membranes (MMMs). The effect of filler loading, gas size, and temperature on the MMMs permeability, diffusivity, and selectivity was investigated. The He permeability increased by a factor of 3, while the He/CO 2 selectivity decreased by a factor of 2, when adding 25 wt % of ZIF-8 at 65 °C to Torlon ® ; similar trends were observed for the case of H 2 . The MMMs permeability and size-selectivity were both enhanced by temperature. The behavior of MMMs is intermediate between the pure polymer and pure filler ones, and can be described with models for composites, indicating that such materials have a good polymer/filler adhesion and their performance could be tailored by acting on the formulation. The behavior observed is in line with previous investigations on MMMs based on glassy polymers and ZIF-8, in similar conditions, and indicates that ZIF-8 can be used as a polymer additive when the permeability is a controlling aspect, with a proper choice of loading and operative temperature.

Objective: Recent studies suggest mental health in youths is deteriorating. The current policy in the United Kingdom emphasizes the role of schools for mental health promotion and prevention, but little data exist on what aspects of schools influence mental health in pupils. This study explored school-level influences on the mental health of young people in a large school-based sample from the United Kingdom., Method: Baseline data from a large cluster randomized controlled trial collected between 2016 and 2018 from mainstream secondary schools selected to be representative in relation to their quality rating, size, deprivation, mixed or single-sex pupil population, and country were analyzed. Participants were pupils in their first or second year of secondary school. The study assessed whether school-level factors were associated with pupil mental health., Results: The study included 26,885 pupils (response rate = 90%; age range, 11‒14 years; 55% female) attending 85 schools in the United Kingdom. Schools accounted for 2.4% (95% CI: 2.0%‒2.8%; p < .0001) of the variation in psychopathology, 1.6% (95% CI: 1.2%‒2.1%; p < .0001) of depression, and 1.4% (95% CI: 1.0%‒1.7%; p < .0001) of well-being. Schools in urban locations, with a higher percentage of free school meals and of White British, were associated with poorer pupil mental health. A more positive school climate was associated with better mental health., Conclusion: School-level variables, primarily related to contextual factors, characteristics of pupil population, and school climate, explain a small but significant amount of variability in mental health of young people. This information might be used to identify schools that are in need of more resources to support mental health of young people., Clinical Trial Registration Information: MYRIAD: My Resilience in Adolescence, a Study Examining the Effectiveness and Cost-Effectiveness of a Mindfulness Training Programme in Schools Compared With Normal School Provision; https://www.isrctn.com/; 86619085., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Evaluating the impacts of population-level interventions (e.g., changes to state legislation) can be challenging as conducting randomized experiments is often impractical and inappropriate, especially in settings where the intervention is implemented in a single, aggregate unit (e.g., a country or state). A common nonrandomized alternative is to compare outcomes in the treated unit(s) with unexposed controls both before and after the intervention. However, the validity of these designs depends on the use of controls that closely resemble the treated unit on before-intervention characteristics and trends on the outcome, and suitable controls may be difficult to find because the number of potential control regions is typically limited. The synthetic control method provides a potential solution to these problems by using a data-driven algorithm to identify an optimal weighted control unit-a "synthetic control"-based on data from before the intervention from available control units. While popular in the social sciences, the method has not garnered as much attention in health research, perhaps due to a lack of accessible texts aimed at health researchers. We address this gap by providing a comprehensive, nontechnical tutorial on the synthetic control method, using a worked example evaluating Florida's "stand your ground" law to illustrate methodological and practical considerations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)