Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

Energetics of a Single Qubit Gate.

Qubits are physical, a quantum gate thus not only acts on the information carried by the qubit but also on its energy. What is then the corresponding flow of energy between the qubit and the controller that implements the gate? Here we exploit a superconducting platform to answer this question in the case of a quantum gate realized by a resonant drive field. During the gate, the superconducting qubit becomes entangled with the microwave drive pulse so that there is a quantum superposition between energy flows. We measure the energy change in the drive field conditioned on the outcome of a projective qubit measurement. We demonstrate that the drive's energy change associated with the measurement backaction can exceed by far the energy that can be extracted by the qubit. This can be understood by considering the qubit as a weak measurement apparatus of the driving field.

An approach to defining and achieving restoration targets for a threatened plant community.

Connecting scientific research and government policy is essential for achieving objectives in sustaining biodiversity in an economic context. Our approach to connecting theoretical ecology, applied ecology, and policy was devised using principles of restoration ecology and the requisite methodology to restore biodiverse ecosystems. Using a threatened ecological community (TEC) with >120 plant species, we posit our approach as a guide for interpreting and achieving regulatory compliance (i.e., government conditions) enacted to manage or offset environmental impacts of development. We inform the scientific approach necessary to delivering outcomes appropriate to policy intent and biodiverse restoration through theoretical and applied research into the ecological restoration of the highly endemic flora of banded ironstone formations of the Mid West of Western Australia. Our approach (1) defines scale-appropriate restoration targets that meet regulatory compliance (e.g., Government of Western Australia Ministerial Conditions); (2) determines the optimal method to return individual plant species to the restoration landscape; (3) develops a conceptual model for our system, based on existing restoration frameworks, to optimize and facilitate the pathway to the restoration of a vegetation community (e.g., TEC) using diverse research approaches; and (4) develops an assessment protocol to compare restoration achievements against the expected regulatory outcomes using our experimental restoration trials as a test example. Our approach systematically addressed the complex challenges in setting and achieving restoration targets for an entire vegetation community, a first for a semiarid environment. We interpret our approach as an industry application relevant to policy- or regulator-mediated mine restoration programs that seek to return biodiverse species assemblages at landscape scales.

Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

Evidence for widespread changes in the structure, composition, and fire regimes of western North American forests.

Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.

Impact of an Australian/New Zealand organisational position statement on extended-release opioid prescribing among surgical inpatients: a dual centre before-and-after study.

Extended-release opioids are often prescribed to manage postoperative pain despite being difficult to titrate to analgesic requirements and their association with long-term opioid use. An Australian/New Zealand organisational position statement released in March 2018 recommended avoiding extended-release opioid prescribing for acute pain. This study aimed to evaluate the impact of this organisational position statement on extended-release opioid prescribing among surgical inpatients. Secondary objectives included predictors and clinical outcomes of prescribing extended-release opioids among surgical inpatients. We conducted a retrospective, dual centre, 11-month before-and-after study and time-series analysis by utilising electronic medical records from two teaching hospitals in Sydney, Australia. The primary outcome was the proportion of patients prescribed an extended-release opioid. For surgical patients prescribed any opioid (n = 16,284), extended-release opioid prescribing decreased after the release of the position statement (38.4% before vs. 26.6% after, p < 0.001), primarily driven by a reduction in extended-release oxycodone (31.1% before vs. 14.1% after, p < 0.001). There was a 23% immediate decline in extended-release opioid prescribing after the position statement release (p < 0.001), followed by an additional 0.2% decline per month in the following months. Multivariable regression showed that the release of the position statement was associated with a decrease in extended-release opioid prescribing (OR 0.54, 95%CI 0.50-0.58). Extended-release opioid prescribing was also associated with increased incidence of opioid-related adverse events (OR 1.52, 95%CI 1.35-1.71); length of stay (RR 1.44, 95%CI 1.39-1.51); and 28-day re-admission (OR 1.26, 95%CI 1.12-1.41). Overall, a reduction in extended-release opioid prescribing was observed in surgical inpatients following position statement release.

Cause of death in adults with intellectual disability in the United States.

BACKGROUND: Prior studies report that adults with intellectual disability (ID) have cause of death patterns distinct from adults in the general population but do not provide comparative analysis by specific causes of death. METHODS: Data are from the National Vital Statistics System 2005-2017 US Multiple Cause-of-Death Mortality files. We utilised adjusted odds ratios to identify causes of death that were more common for adults whose death certificate indicated ID (N = 22 512) than for adults whose death certificate did not indicate ID (N = 32 738 229), controlling for severity level of ID. We then examine the associations between biological sex and race-ethnicity and causes of death solely among adults with ID. RESULTS: The leading cause of death for adults with and without ID indicated on their death certificate was heart disease. Adults with ID, regardless of the severity of the disability, had substantially higher risk of death from pneumonitis, influenza/pneumonia and choking. Adults with mild/moderate ID also had higher risk of death from diabetes mellitus. Differences in cause of death trends were associated with biological sex and race-ethnicity. CONCLUSIONS: Efforts to reduce premature mortality for adults with ID should attend to risk factors for causes of death typical in the general population such as heart disease and cancer, but also should be cognisant of increased risk of death from choking among all adults with ID, and diabetes among adults with mild/moderate ID. Further research is needed to better understand the factors determining comparatively lower rates of death from neoplasms and demographic differences in causes of death among adults with ID.

Facial width-to-height ratio is associated with agonistic and affiliative dominance in bonobos (Pan paniscus).

Facial width-to-height ratio (fWHR) is associated with social dominance in human and non-human primates, which may reflect the effects of testosterone on facial morphology and behaviour. Given that testosterone facilitates status-seeking motivation, the association between fWHR and behaviour should be contingent on the relative costs and benefits of particular dominance strategies across species and socioecological contexts. We tested this hypothesis in bonobos (Pan paniscus), who exhibit female dominance and rely on both affiliation and aggression to achieve status. We measured fWHR from facial photographs, affiliative dominance with Assertiveness personality scores and agonistic dominance with behavioural data. Consistent with our hypothesis, agonistic and affiliative dominance predicted fWHR in both sexes independent of age and body weight, supporting the role of status-seeking motivation in producing the link between fWHR and socioecologically relevant dominance behaviour across primates.

The toad fly Lucilia bufonivora: its evolutionary status and molecular identification.

The blow fly genus Lucilia is composed largely of saprophages and facultative myasis agents, including the economically important species Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) and Lucilia sericata (Meigen). Only one species is generally recognized as an obligate agent of myiasis, Lucilia bufonivora Moniez, and this is an obligate parasite of toads. Lucilia silvarum (Meigen), a sister species, behaves mainly as a carrion breeder; however, it has also been reported as a facultative parasite of amphibians. Morphologically, these species are almost identical, and historically this has led to misidentification, taxonomic ambiguity and a paucity of studies of L. bufonivora. In this study, dipterous larvae were analysed from toad myiasis cases from the U.K., The Netherlands and Switzerland, together with adult specimens of fly species implicated in amphibian parasitism: L. bufonivora, L. silvarum and Lucilia elongata Shannon (from North America). Partial sequences of two genes, cox1 and ef1α, were amplified. Seven additional blow fly species were analysed as outgroups. Bayesian inference trees of cox1, ef1α and a combined-gene dataset were constructed. All larvae isolated from toads were identified as L. bufonivora and no specimens of L. silvarum were implicated in amphibian myiasis. This study confirms L. silvarum and L. bufonivora as distinct sister species and provides unambiguous molecular identification of L. bufonivora.

Spatial and temporal habitat partitioning by calliphorid blowflies.

Calliphorid blowflies perform an essential ecosystem service in the consumption, recycling and dispersion of carrion nutrients and are considered amongst the most important functional groups in an ecosystem. Some species are of economic importance as facultative agents of livestock myiasis. The interspecific ecological differences that facilitate coexistence within the blowfly community are not fully understood. The aim of this work was to quantify differences in habitat use by calliphorid species. Thirty traps were distributed among three habitats at two sites in southwest England for collections made during March-August 2016. A total of 17 246 specimens were caught, of which 2427 were Lucilia sericata, 51 Lucilia richardsi, 6580 Lucilia caesar, 307 Lucilia ampullacea, 4881 Calliphora vicina and 2959 Calliphora vomitoria (all: Diptera: Calliphoridae). Lucilia sericata was the dominant species in open habitats, whereas L. caesar was the most abundant species in shaded habitats. Calliphora specimens were more abundant in the cooler months. These findings suggest that Calliphora and Lucilia species show strong temporal segregation mediated by temperature, and that species of the genus Lucilia show differences in the use of habitats that are likely to be driven by differences in humidity tolerance and light intensity. These factors in combination result in effective niche partitioning.

A sustainable method to reduce postoperative oxycodone discharge prescribing in a metropolitan tertiary referral hospital.

The primary objective of this quality improvement project was to measure and reduce the number of oxycodone immediate-release tablets dispensed to overnight stay surgical patients at discharge. The secondary objective was to reduce the proportion of inappropriate oxycodone immediate-release prescriptions at discharge. Interrupted time series analysis was performed in four surgical wards of St Vincent's Public Hospital, Sydney. The baseline period was from January 2005 to August 2013. Interventions and follow-up occurred until July 2017. Baseline audit of oxycodone immediate-release tablet numbers showed prescribing increased significantly with a monthly linear trend of 1.8 (95%CI = 1.4-2.3; p = 0.001) tablets/100 surgical admissions from January 2005 to August 2013. Four sequential interventions produced no significant change in the primary objective. At the end of the first month of a fifth intervention, comprising audit-feedback plus individual academic detailing, the average number of oxycodone tablets decreased by 77 (95%CI 39-115) tablets/100 surgical cases, and the postintervention linear trend was a monthly reduction of 3.2 (coefficient -3.2 (95%CI -4.5 to -1.8); p = 0.001) tablets/100 surgical admissions. Baseline audit showed 27% of oxycodone prescriptions to be inappropriate. Following our intervention, this dropped to 17% (p = 0.048), and then to 10% (p = 0.002) after 3 years.

Heterogeneity in age at death for adults with developmental disability.

BACKGROUND: Although increased attention has been devoted to mortality trends for adults with developmental disability, research has not accounted for possible differences in age at death between disability types. We examine whether heterogeneity is present in age at death between adults with different types of developmental disability. METHODS: Data were from the 2012-2016 U.S. Multiple Cause-of-Death Mortality files. Mean age at death and age at death distributions were analysed for adults, aged 18-126, with and without developmental disability collectively and then stratified by biological sex. RESULTS: There were 33 154 decedents with and 13 026 759 without developmental disability. Compared with adults without developmental disability, age at death was lower for all decedents with developmental disability but varied markedly by disability type and biological sex. Among adults with developmental disability, those with intellectual disability had the highest age at death, and those with cerebral palsy or other rare developmental disabilities, especially if co-morbid for a second developmental disability, had the lowest age at death. CONCLUSION: Research on age at death for adults with developmental disability must account for heterogeneity among disability types in order to ensure reliable estimates. Failure to do so conceals important differences between disability types, which can misguide public health and preventive care efforts to reduce premature mortality and/or provide aging-related supports.

Integrated Effects of Genetic Resistance and Prothioconazole + Tebuconazole Application Timing on Fusarium Head Blight in Wheat.

Integrated Fusarium head blight (FHB) management programs consisting of different combinations of cultivar resistance class and an application of the fungicide prothioconazole + tebuconazole at or after 50% early anthesis were evaluated for efficacy against FHB incidence (INC; percentage of diseased spikes), index (IND; percentage of diseased spikelets per spike), Fusarium damaged kernel (FDK), deoxynivalenol (DON) toxin contamination, grain yield, and test weight (TW) in inoculated field trials conducted in 11 U.S. states in 2014 and 2015. Mean log response ratios and corresponding percent control values for INC, IND, FDK, and DON, and mean differences in yield and TW relative to a nontreated, inoculated susceptible check (S_CK), were estimated through network meta-analyses as measures of efficacy. Results from the analyses were then used to estimate the economic benefit of each management program for a range of grain prices and fungicide applications costs. Management programs consisting of a moderately resistant (MR) cultivar treated with the fungicide were the most efficacious, reducing INC by 60 to 69%, IND by 71 to 76%, FDK by 66 to 72%, and DON by 60 to 64% relative to S_CK, compared with 56 to 62% for INC, 68 to 72% for IND, 66 to 68% for FDK, and 58 to 61% for DON for programs with a moderately susceptible (MS) cultivar. The least efficacious programs were those with a fungicide application to a susceptible (S) cultivar, with less than a 45% reduction of INC, IND, FDK, or DON. All programs were more efficacious under conditions favorable for FHB compared with less favorable conditions, with applications made at 50% early anthesis being of comparable efficacy to those made 2 to 7 days later. Programs with an MS cultivar resulted in the highest mean yield increases relative to S_CK (541 to 753 kg/ha), followed by programs with an S cultivar (386 to 498 kg/ha) and programs with an MR cultivar (250 to 337 kg/ha). Integrated management programs with an MS or MR cultivar treated with the fungicide at or after 50% early anthesis were the most likely to result in a 50 or 75% control of IND, FDK, or DON in a future trial. At a fixed fungicide application cost, these programs were $4 to $319/MT more economically beneficial than corresponding fungicide-only programs, depending on the cultivar and grain price. These findings demonstrate the benefits of combining genetic resistance with a prothioconazole + tebuconazole treatment to manage FHB, even if that treatment is applied a few days after 50% early anthesis.

Incidence of components of metabolic syndrome in the metabolically healthy obese over 9 years follow-up: the Atherosclerosis Risk In Communities study.

BACKGROUND: Some obese adults are not afflicted by the metabolic abnormalities often associated with obesity (the 'metabolically healthy obese' (MHO)); however, they may be at increased risk of developing cardiometabolic abnormalities in the future. Little is known about the relative incidence of individual components of metabolic syndrome (MetSyn). METHODS: We used data from a multicenter, community-based cohort aged 45-64 years at recruitment (the Atherosclerosis Risk In Communities study) to examine the first appearance of any MetSyn component, excluding waist circumference. Body mass index (BMI, kg m-2) and cardiometabolic data were collected at four triennial visits. Our analysis included 3969 adults who were not underweight and free of the components of MetSyn at the initial visit. Participants were classified as metabolically healthy normal weight (MHNW), overweight (MHOW) and MHO at each visit. Adjusted hazard ratios (HR) and 95% confidence intervals were estimated with proportional hazards regression models. RESULTS: The relative rate of developing each risk factor was higher among MHO than MHNW, with the strongest association noted for elevated fasting glucose (MHO vs MHNW, HR: 2.33 (1.77, 3.06)). MHO was also positively associated with elevated triglycerides (HR: 1.63 (1.27, 2.09)), low high-density lipoprotein-cholesterol (HR: 1.68 (1.32, 2.13)) and elevated blood pressure (HR: 1.54 (1.26, 1.88)). A similar, but less pronounced pattern was noted among the MHOW vs MHNW. CONCLUSIONS: We conclude that even among apparently healthy individuals, obesity and overweight are related to more rapid development of at least one cardiometabolic risk factor, and that elevations in blood glucose develop most rapidly.

Toxicogenomic module associations with pathogenesis: a network-based approach to understanding drug toxicity.

Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP'). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses complement traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.

Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs.

Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10-8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.