The genomic origins of the world's first farmers.

The precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation, remain largely unknown. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness. This modeling elucidates the demographic processes at the root of the Neolithic transition and leads to a spatial interpretation of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene.

Cycles of satellite and transposon evolution in Arabidopsis centromeres.

Centromeres are critical for cell division, loading CENH3 or CENPA histone variant nucleosomes, directing kinetochore formation and allowing chromosome segregation1,2. Despite their conserved function, centromere size and structure are diverse across species. To understand this centromere paradox3,4, it is necessary to know how centromeric diversity is generated and whether it reflects ancient trans-species variation or, instead, rapid post-speciation divergence. To address these questions, we assembled 346 centromeres from 66 Arabidopsis thaliana and 2 Arabidopsis lyrata accessions, which exhibited a remarkable degree of intra- and inter-species diversity. A. thaliana centromere repeat arrays are embedded in linkage blocks, despite ongoing internal satellite turnover, consistent with roles for unidirectional gene conversion or unequal crossover between sister chromatids in sequence diversification. Additionally, centrophilic ATHILA transposons have recently invaded the satellite arrays. To counter ATHILA invasion, chromosome-specific bursts of satellite homogenization generate higher-order repeats and purge transposons, in line with cycles of repeat evolution. Centromeric sequence changes are even more extreme in comparison between A. thaliana and A. lyrata. Together, our findings identify rapid cycles of transposon invasion and purging through satellite homogenization, which drive centromere evolution and ultimately contribute to speciation.

An oxygen-sensing mechanism for angiosperm adaptation to altitude.

Flowering plants (angiosperms) can grow at extreme altitudes, and have been observed growing as high as 6,400 metres above sea level1,2; however, the molecular mechanisms that enable plant adaptation specifically to altitude are unknown. One distinguishing feature of increasing altitude is a reduction in the partial pressure of oxygen (pO2). Here we investigated the relationship between altitude and oxygen sensing in relation to chlorophyll biosynthesis-which requires molecular oxygen3-and hypoxia-related gene expression. We show that in etiolated seedlings of angiosperm species, steady-state levels of the phototoxic chlorophyll precursor protochlorophyllide are influenced by sensing of atmospheric oxygen concentration. In Arabidopsis thaliana, this is mediated by the PLANT CYSTEINE OXIDASE (PCO) N-degron pathway substrates GROUP VII ETHYLENE RESPONSE FACTOR transcription factors (ERFVIIs). ERFVIIs positively regulate expression of FLUORESCENT IN BLUE LIGHT (FLU), which represses the first committed step of chlorophyll biosynthesis, forming an inactivation complex with tetrapyrrole synthesis enzymes that are negatively regulated by ERFVIIs, thereby suppressing protochlorophyllide. In natural populations representing diverse angiosperm clades, we find oxygen-dependent altitudinal clines for steady-state levels of protochlorophyllide, expression of inactivation complex components and hypoxia-related genes. Finally, A. thaliana accessions from contrasting altitudes display altitude-dependent ERFVII activity and accumulation. We thus identify a mechanism for genetic adaptation to absolute altitude through alteration of the sensitivity of the oxygen-sensing system.

Pan-European study of genotypes and phenotypes in the Arabidopsis relative Cardamine hirsuta reveals how adaptation, demography, and development shape diversity patterns.

We study natural DNA polymorphisms and associated phenotypes in the Arabidopsis relative Cardamine hirsuta. We observed strong genetic differentiation among several ancestry groups and broader distribution of Iberian relict strains in European C. hirsuta compared to Arabidopsis. We found synchronization between vegetative and reproductive development and a pervasive role for heterochronic pathways in shaping C. hirsuta natural variation. A single, fast-cycling ChFRIGIDA allele evolved adaptively allowing range expansion from glacial refugia, unlike Arabidopsis where multiple FRIGIDA haplotypes were involved. The Azores islands, where Arabidopsis is scarce, are a hotspot for C. hirsuta diversity. We identified a quantitative trait locus (QTL) in the heterochronic SPL9 transcription factor as a determinant of an Azorean morphotype. This QTL shows evidence for positive selection, and its distribution mirrors a climate gradient that broadly shaped the Azorean flora. Overall, we establish a framework to explore how the interplay of adaptation, demography, and development shaped diversity patterns of 2 related plant species.

Inference of Locus-Specific Population Mixtures from Linked Genome-Wide Allele Frequencies.

Admixture between populations and species is common in nature. Since the influx of new genetic material might be either facilitated or hindered by selection, variation in mixture proportions along the genome is expected in organisms undergoing recombination. Various graph-based models have been developed to better understand these evolutionary dynamics of population splits and mixtures. However, current models assume a single mixture rate for the entire genome and do not explicitly account for linkage. Here, we introduce TreeSwirl, a novel method for inferring branch lengths and locus-specific mixture proportions by using genome-wide allele frequency data, assuming that the admixture graph is known or has been inferred. TreeSwirl builds upon TreeMix that uses Gaussian processes to estimate the presence of gene flow between diverged populations. However, in contrast to TreeMix, our model infers locus-specific mixture proportions employing a hidden Markov model that accounts for linkage. Through simulated data, we demonstrate that TreeSwirl can accurately estimate locus-specific mixture proportions and handle complex demographic scenarios. It also outperforms related D- and f-statistics in terms of accuracy and sensitivity to detect introgressed loci.

The trichome pattern diversity of Cardamine shares genetic mechanisms with Arabidopsis but differs in environmental drivers.

Natural variation in trichome pattern (amount and distribution) is prominent among populations of many angiosperms. However, the degree of parallelism in the genetic mechanisms underlying this diversity and its environmental drivers in different species remain unclear. To address these questions, we analyzed the genomic and environmental bases of leaf trichome pattern diversity in Cardamine hirsuta, a relative of Arabidopsis (Arabidopsis thaliana). We characterized 123 wild accessions for their genomic diversity, leaf trichome patterns at different temperatures, and environmental adjustments. Nucleotide diversities and biogeographical distribution models identified two major genetic lineages with distinct demographic and adaptive histories. Additionally, C. hirsuta showed substantial variation in trichome pattern and plasticity to temperature. Trichome amount in C. hirsuta correlated positively with spring precipitation but negatively with temperature, which is opposite to climatic patterns in A. thaliana. Contrastingly, genetic analysis of C. hirsuta glabrous accessions indicated that, like for A. thaliana, glabrousness is caused by null mutations in ChGLABRA1 (ChGL1). Phenotypic genome-wide association studies (GWAS) further identified a ChGL1 haplogroup associated with low trichome density and ChGL1 expression. Therefore, a ChGL1 series of null and partial loss-of-function alleles accounts for the parallel evolution of leaf trichome pattern in C. hirsuta and A. thaliana. Finally, GWAS also detected other candidate genes (e.g. ChETC3, ChCLE17) that might affect trichome pattern. Accordingly, the evolution of this trait in C. hirsuta and A. thaliana shows partially conserved genetic mechanisms but is likely involved in adaptation to different environments.

Nicotine dependence and incident psychiatric disorders: prospective evidence from US national study.

We examined the prospective associations between nicotine dependence and the likelihood of psychiatric and substance use disorders in the general adult population. Participants came from a nationally representative sample of US adults aged 18 years or older, who were interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001-2002; Wave 2, 2004-2005). The primary analyses were limited to 32,671 respondents (13,751 male (47.9% weighted); mean age of 45 years (SD = 0.18)) who were interviewed in both waves. We used multiple regression and propensity score matching (PSM) to estimate the strength of independent associations between nicotine dependence related to the use of tobacco products at Wave 1 and incident psychiatric disorders at Wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). All analyses adjusted for multiple potential confounders, including childhood (family history of substance use disorders, parental loss, vulnerable family environment), early-adolescence (self-esteem, social deviance, conduct disorder), late-adolescence (education, personality and psychiatric disorders), adulthood (divorce, stressful life events, social deviance, quality of life, history of alcohol or other substance use disorder), and sociodemographic factors. Multiple regression analysis and PSM converged in indicating that nicotine dependence was associated with significantly increased incidence of any psychiatric disorder (OR = 1.39(95%CI:1.20;1.60)), including substance use disorders (OR = 1.91(95%CI:1.47;2.47)), and anxiety disorders (OR = 1.31(95%CI:1.06;1.62)). Population Attributable Risk Proportions were substantial, ranging from 12.5%(95%CI:8.10;17.0) for any psychiatric disorder to 33.3%(95%CI:18.7;48.0) for any other drug use disorder. Supplementary analyses also indicated significant associations between nicotine dependence and persistence of psychiatric and substance use disorders among patients having a disorder at Wave 1. In the general adult population, nicotine dependence is associated with an increased likelihood for several psychiatric and substance use disorders. Given its high prevalence, these findings have important public health implications.

Trends in Psychological Distress and Outpatient Mental Health Care of Adults During the COVID-19 Era.

BACKGROUND: In addition to the physical disease burden of the COVID-19 pandemic, concern exists over its adverse mental health effects. OBJECTIVE: To characterize trends in psychological distress and outpatient mental health care among U.S. adults from 2018 to 2021 and to describe patterns of in-person, telephone, and video outpatient mental health care. DESIGN: Cross-sectional nationally representative survey of noninstitutionalized adults. SETTING: United States. PARTICIPANTS: Adults included in the Medical Expenditure Panel Survey Household Component, 2018 to 2021 (n = 86 658). MEASUREMENTS: Psychological distress was measured with the Kessler-6 scale (range of 0 to 24, with higher scores indicating more severe distress), with a score of 13 or higher defined as serious psychological distress, 1 to 12 as less serious distress, and 0 as no distress. Outpatient mental health care use was measured via computer-assisted personal interviews. RESULTS: Between 2018 and 2021, the rate of serious psychological distress among adults increased from 3.5% to 4.2%. Although the rate of outpatient mental health care increased from 11.2% to 12.4% overall, the rate decreased from 46.5% to 40.4% among adults with serious psychological distress. When age, sex, and distress were controlled for, a significant increase in outpatient mental health care was observed for young adults (aged 18 to 44 years) but not middle-aged (aged 45 to 64 years) and older (aged >65 years) adults and for employed adults but not unemployed adults. In 2021, 33.4% of mental health outpatients received at least 1 video visit, including a disproportionate percentage of young, college-educated, higher-income, employed, and urban adults. LIMITATION: Information about outpatient mental health service modality (in-person, video, telephone) was first fully available in the 2021 survey. CONCLUSION: These trends and patterns underscore the persistent challenges of connecting older adults, unemployed persons, and seriously distressed adults to outpatient mental health care and the difficulties faced by older, less educated, lower-income, unemployed, and rural patients in accessing outpatient mental health care via video. PRIMARY FUNDING SOURCE: None.

Geographical distance predicts psychiatric treatment retention for Hispanic women with comorbid major depression and breast cancer.

PURPOSE: Depression is among the most common comorbid psychiatric disorders of patients with breast cancer. Depression decreases patient quality of life and, if untreated, can adversely affect cancer treatment. We sought to identify treatment barriers for women with breast cancer receiving psychotherapy for depression. Findings may help policy makers and researchers determine funding and design of future studies involving this population, especially in communities with high rates of health disparities. METHODS: We used data from a randomized trial for women with breast cancer and current DSM-IV non-psychotic unipolar major depressive disorder (MDD). Patients were randomly assigned to 12 weeks of one of three psychotherapies and attrition was assessed by whether subjects completed 12 weekly treatment sessions. We used descriptive analyses and logistic regression to identify treatment barriers. R shiny was used to determine study patient residences. RESULTS: Of 134 randomized patients, 84 (62.7%) were Hispanic. Fifty-nine patients (44%) either did not start or dropped out of treatment, 49 (83.1%) of them being Hispanic. Being a Hispanic woman, less educated, and geographically distant from treatment significantly predicted attrition. Single Hispanic mothers had significantly higher attrition risk than married and/or childless women. CONCLUSION: Identifying barriers to treatment is important to improve treatment adherence for patients with concurrent diagnoses of breast cancer and MDD, especially for traditionally underserved minorities. Additional support such as affordable tele-medicine, multi-language assistance, financial aid for transportation and child-care, and allocation of more funds to address some identified barriers deserve consideration to improve treatment adherence and outcomes.

MYB transcription factors drive evolutionary innovations in Arabidopsis fruit trichome patterning.

Both inter- and intra-specific diversity has been described for trichome patterning in fruits, which is presumably involved in plant adaptation. However, the mechanisms underlying this developmental trait have been hardly addressed. Here we examined natural populations of Arabidopsis (Arabidopsis thaliana) that develop trichomes in fruits and pedicels, phenotypes previously not reported in the Arabidopsis genus. Genetic analyses identified five loci, MALAMBRUNO 1-5 (MAU1-5), with MAU2, MAU3, and MAU5 showing strong epistatic interactions that are necessary and sufficient to display these traits. Functional characterization of these three loci revealed cis-regulatory mutations in TRICHOMELESS1 and TRIPTYCHON, as well as a structural mutation in GLABRA1. Therefore, the multiple mechanisms controlled by three MYB transcription factors of the core regulatory network for trichome patterning have jointly been modulated to trigger trichome development in fruits. Furthermore, analyses of worldwide accessions showed that these traits and mutations only occur in a highly differentiated relict lineage from the Iberian Peninsula. In addition, these traits and alleles were associated with low spring precipitation, which suggests that trichome development in fruits and pedicels might be involved in climatic adaptation. Thus, we show that the combination of synergistic mutations in a gene regulatory circuit has driven evolutionary innovations in fruit trichome patterning in Arabidopsis.

Search for Dark Matter Ionization on the Night Side of Jupiter with Cassini.

We present a new search for dark matter (DM) using planetary atmospheres. We point out that annihilating DM in planets can produce ionizing radiation, which can lead to excess production of ionospheric H_{3}^{+}. We apply this search strategy to the night side of Jupiter near the equator. The night side has zero solar irradiation, and low latitudes are sufficiently far from ionizing auroras, leading to a low-background search. We use Cassini data on ionospheric H_{3}^{+} emission collected three hours either side of Jovian midnight, during its flyby in 2000, and set novel constraints on the DM-nucleon scattering cross section down to about 10^{-38} cm^{2}. We also highlight that DM atmospheric ionization may be detected in Jovian exoplanets using future high-precision measurements of planetary spectra.

Allergic inflammation triggers dyslipidemia via IgG signalling.

BACKGROUND: Allergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. METHODS: We used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell-depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post-allergen challenge. Also, changes in serum triglycerides (TGs) were evaluated in a group of 59 patients ≥14 days after the onset of an allergic reaction. RESULTS: We found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TGs and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T-cell-driven late phase inflammation. On the contrary, the IgG-mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TGs in 59 patients after undergoing an allergic reaction. CONCLUSION: Overall, this study reveals that IgG-mediated allergic inflammation regulates lipid metabolism.

Copolymerization of ß-Butyrolactones into Functionalized Polyhydroxyalkanoates Using Aluminum Catalysts: Influence of the Initiator in the Ring-Opening Polymerization Mechanism.

Within bioplastics, natural poly(3-hydroxybutyrate) (PHB) stands out as fully biocompatible and biodegradable, even in marine environments; however, its high isotacticity and crystallinity limits its mechanical properties and hence its applications. PHB can also be synthesized with different tacticities via a catalytic ring-opening polymerization (ROP) of rac-ß-butyrolactone (BBL), paving the way to PHB with better thermomechanical and processability properties. In this work, the catalyst family is extended based on aluminum phenoxy-imine methyl catalyst [AlMeL2], that reveals efficient in the ROP of BBL, to the halogeno analogous complex [AlClL2]. As well, the impact on the ROP mechanism of different initiators is further explored with a particular focus in dimethylaminopyridine (DMAP), a hardly studied initiator for the ROP of BBL. A thorough mechanistic study is performed that evidences the presence of two concomitant DMAP-mediated mechanisms, that lead to either a DMAP or a crotonate end-capping group. Besides, in order to increase the possibilities of PHB post-polymerization functionalization, the introduction of a side-chain functionality is explored, establishing the copolymerization of BBL with ß-allyloxymethylene propiolactone (BPLOAll), resulting in well-defined P(BBL-co-BPLOAll) copolymers.

Fatal Drug Overdose Risks of Health Care Workers in the United States : A Population-Based Cohort Study.

BACKGROUND: Despite an unprecedented increase in drug overdose deaths in the United States, the risks faced by U.S. health care workers, who often have access to controlled prescription drugs, are not known. OBJECTIVE: To estimate risks for drug overdose death among health care workers relative to non-health care workers. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: Health care workers (n = 176 000) and non-health care workers (n = 1 662 000) aged 26 years or older surveyed in 2008 and followed for cause of death through 2019. MEASUREMENTS: Age- and sex-standardized drug overdose deaths were determined for 6 health care worker groups (physicians, registered nurses, other treating or diagnosing health care workers, health technicians, health care support workers, and social or behavioral health workers) and non-health care workers. Adjusted drug overdose death hazards (and 95% CIs) were also evaluated, with adjustment for age, sex, race/ethnicity, marital status, education, income, urban or rural residence, and region. RESULTS: Approximately 0.07% of our study sample died of a drug overdose during follow-up. Among health care workers, annual standardized rates of drug overdose death per 100 000 persons ranged from 2.3 (95% CI, 0 to 4.8) for physicians to 15.5 (CI, 9.8 to 21.2) for social or behavioral health workers. Compared with those for non-health care workers, the adjusted hazards of total drug overdose death were significantly increased for social or behavioral health workers (adjusted hazard ratio, 2.55 [CI, 1.74 to 3.73]), registered nurses (adjusted hazard ratio, 2.22 [CI, 1.57 to 3.13]), and health care support workers (adjusted hazard ratio, 1.60 [CI, 1.19 to 2.16]), but not for physicians (adjusted hazard ratio, 0.61 [CI, 0.19 to 1.93]), other treating or diagnosing health care workers (adjusted hazard ratio, 0.93 [CI, 0.44 to 1.95]), or health technicians (adjusted hazard ratio, 1.13 [CI, 0.75 to 1.68]). Results were generally similar for opioid-related overdose deaths and unintentional overdose deaths. LIMITATION: Unmeasured confounding, uncertain validity of cause of death, and one-time assessment of occupation. CONCLUSION: Registered nurses, social or behavioral health workers, and health care support workers were at increased risk for drug overdose death, suggesting the need to identify and intervene on those at high risk. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Toward a generalized developmental model of psychopathological liabilities and psychiatric disorders.

BACKGROUND: Most psychiatric disorders are associated with several risk factors, but a few underlying psychopathological dimensions account for the common co-occurrence of disorders. If these underlying psychopathological dimensions mediate associations of the risk factors with psychiatric disorders, it would support a trans-diagnostic orientation to etiological research and treatment development. METHOD: An analysis was performed of the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a US nationally representative sample of non-institutionalized civilian adults, focusing on respondents who were aged ⩾21 (n = 34 712). Structural equation modeling was used to identify the psychopathological dimensions underlying psychiatric disorders; to examine associations between risk factors, psychopathological dimensions and individual disorders; and to test whether associations of risk factors occurring earlier in life were mediated by risk factors occurring later in life. RESULTS: A bifactor model of 13 axis I disorders provided a good fit (CFI = 0.987, TLI = 0.982, and RMSEA = 0.011) including an overall psychopathology factor as measured by all 13 disorders and 2 specific factors, one for externalizing disorders and one for fear-related disorders. A substantial proportion of the total effects of the risk factors occurring early in life were indirectly mediated through factors occurring later in life. All risk factors showed a significant total effect on the general psychopathology, externalizing and fear-related factors. Only 23 of 325 direct associations of risk factors with psychiatric disorders achieved statistical significance. CONCLUSION: Most risk factors for psychiatric disorders are mediated through broad psychopathological dimensions. The central role of these dimensions supports trans-diagnostic etiological and intervention research.

Data needs and models for the opioid epidemic.

The evolving nature of the opioid epidemic and continued increases in overdose deaths highlight a need for fundamental change in the collection and use of surveillance data to link them to implementation of effective service, treatment, and prevention approaches. Yet at present, the quality and timeliness of US surveillance data often limits data-driven approaches. We review current information needs, summarize limitations of existing data, propose complementary surveillance resources, and provide examples of promising approaches designed to meet the needs of data end-users. We conclude that there is a need for an approach that focuses on the needs of data end-users, such as public health systems leaders, policy makers, public, nonprofit and prepaid healthcare systems, and other systems, such as the justice system. Such an approach, which may require investments in new infrastructure, should prioritize improvements in data timeliness, sample representativeness, database linkage, and increased flexibility to adapt to shifts in the environment, while preserving the privacy of survey participants. Use of simulations, distributed research and data networks, alternative data sources, such as wastewater or digital data collection and use of blockchain technology, are some of promising avenues toward an improved and more user-centered surveillance system.

Psychiatric symptoms and mortality in older adults with major psychiatric disorders: results from a multicenter study.

Prior research suggests that certain psychiatric symptoms could be associated with increased risk of death. However, it remains unclear whether this association could rely on all or specific symptoms. In this report, we used data from a multicenter 5-year prospective study (N = 641) of older adults with an ICD-10 diagnosis of schizophrenia, bipolar disorder or major depressive disorder, recruited from French community psychiatric departments. We used a latent variable approach to disentangle the effects shared by all psychiatric symptoms (i.e., general psychopathology factor) and those specific to individual psychiatric symptoms, while adjusting for sociodemographic and clinical factors. Psychiatric symptoms were assessed face-to-face by psychiatrists trained to semi-structured interviews using the Brief Psychiatric Rating Scale (BPRS). Among older adults with major psychiatric disorders, we found that all psychiatric symptoms were associated with increased mortality, and that their effect on the 5-year mortality were exerted mostly through a general psychopathology dimension (ß = 0.13, SE = 0.05, p < 0.05). No BPRS item or lower order factor had a significant effect on mortality beyond and above the effect of the general psychopathology factor. Greater number of medical conditions, older age, male sex, and being hospitalized or institutionalized at baseline were significantly associated with this risk beyond the effect of the general psychopathology factor. Since psychiatric symptoms may affect mortality mainly through a general psychopathology dimension, biological and psychological mechanisms underlying this dimension should be considered as promising targets for interventions to decrease excess mortality of older individuals with psychiatric disorders.

Impact of lithium on mortality among older adults with major psychiatric disorders: A 5-year prospective multicenter study.

OBJECTIVE: Prior studies report conflicting results about the association between lithium use and all-cause mortality. In addition, data are scarce on this association among older adults with psychiatric disorders. In this report, we sought to examine the associations of lithium use with all-cause mortality and specific causes of death (i.e., due to cardiovascular disorder, non-cardiovascular disease, accident, or suicide) among older adults with psychiatric disorders during a 5-year follow-up period. METHODS: In this observational epidemiological study, we used data from 561 patients belonging to a Cohort of individuals with Schizophrenia or Affective disorders aged 55-years or more (CSA). Patients taking lithium at baseline were first compared to patients not taking lithium, and then to patients taking (i) antiepileptics and (ii) atypical antipsychotics in sensitivity analyses. Analyses were adjusted for socio-demographic (e.g., age, gender), clinical characteristics (e.g., psychiatric diagnosis, cognitive functioning), and other psychotropic medications (e.g. benzodiazepines). RESULTS: There was no significant association between lithium use and all-cause mortality [AOR=1.12; 95%CI=0.45-2.79; p=0.810] or disease-related mortality [AOR=1.37; 95%CI=0.51-3.65; p=0.530]. None of the 44 patients taking lithium died from suicide, whereas 4.0% (N=16) of patients not receiving lithium did. CONCLUSION: These findings suggest that lithium may not be associated with all-cause or disease-related mortality and might be associated with reduced risk of suicide in this population. They argue against the underuse of lithium as compared with antiepileptics and atypical antipsychotics among older adults with mood disorders.

HEAL Preventing Opioid Use Disorder: a Vision for Research to Increase Access to Prevention Services.

Launched in 2018, the National Institutes of Health (NIH) Helping to End Addiction Long-term Initiative®, or NIH HEAL Initiative, is an aggressive effort to speed scientific solutions to stem this national public health crisis. Investments in new strategies to prevent opioid misuse are a key component of this comprehensive response to the opioid epidemic. In 2019, funded through the NIH HEAL Initiative® and administered by the National Institute on Drug Abuse (NIDA), HEAL Preventing Opioid Use Disorder (HEAL Preventing OUD) research program began, filling the gap of needed upstream prevention interventions. The vision for HEAL Preventing OUD is that: Healthcare organizations and public systems will be able to make evidence-based preventive intervention services accessible to all persons who experience risk for opioid and other substance misuse or use disorder. Realizing this vision will require research investments in four strategic areas: (1) risk identification; (2) intervention development; (3) social determinants, health equity, and policy; and (4) dissemination, implementation, scale up, and sustainment. There exists tremendous potential for prevention to be a viable solution for the ongoing opioid crisis, particularly through investments in upstream, equitable, and sustainable prevention services.

Visual Parking Occupancy Detection Using Extended Contextual Image Information via a Multi-Branch Output ConvNeXt Network.

Along with society's development, transportation has become a key factor in human daily life, increasing the number of vehicles on the streets. Consequently, the task of finding free parking slots in metropolitan areas can be dramatically challenging, increasing the chance of getting involved in an accident and the carbon footprint, and negatively affecting the driver's health. Therefore, technological resources to deal with parking management and real-time monitoring have become key players in this scenario to speed up the parking process in urban areas. This work proposes a new computer-vision-based system that detects vacant parking spaces in challenging situations using color imagery processed by a novel deep-learning algorithm. This is based on a multi-branch output neural network that maximizes the contextual image information to infer the occupancy of every parking space. Every output infers the occupancy of a specific parking slot using all the input image information, unlike existing approaches, which only use a neighborhood around every slot. This allows it to be very robust to changing illumination conditions, different camera perspectives, and mutual occlusions between parked cars. An extensive evaluation has been performed using several public datasets, proving that the proposed system outperforms existing approaches.