Autistic people differ from non-autistic people subjectively, but not objectively in their reasoning.

LAY ABSTRACT: Autistic people often experience challenges in social contexts, and when decisions need to be made quickly. There is evidence showing that autistic people have a tendency for greater deliberation and lower intuition, compared to non-autistic people. This has led to the researchers' proposal that autism is associated with an enhanced level of rationality. However, these theories have been mostly explored through the lens of either only non-social domain or only social domain. To address this gap, we recruited autistic adults and carefully matched them with non-autistic adults for comparison. We used a task representing both social and non-social interactions in a comparison structure and asked participants' moral judgements on scenarios' main characters. This was complemented by subjective and objective measures of reasoning. Our findings did not reveal meaningful differences between groups in terms of deliberation. However, we did observe that autistic participants self-reported lower levels of intuition, compared to non-autistic participants. Autistic people consistently rate themselves as less intuitive than their counterparts. Nevertheless, objective evidence supporting this across tasks and studies is inconsistent.

Testicular self-examination: The role of anticipated relief and anticipated regret.

OBJECTIVE: Anticipated regret has been implicated in health-related decision-making. Recent work on influenza vaccination has suggested that anticipated relief, too, may influence individuals' decisions to engage in positive health behaviours. To explore these affective components further and address the generality of possible mechanisms underlying these associations, we examined whether anticipated relief and anticipated regret independently predict testicular self-examination (TSE) intention and behaviour. Given claims about differences in their nature and function, we distinguished between counterfactual relief (relief that a worse outcome did not obtain) and temporal relief (relief that an unpleasant experience is over). DESIGN: Prospective correlational. METHODS: At Time 1 (July 2022), 567 cis-gendered males were asked to complete measures of anticipated regret, anticipated counterfactual and temporal relief, measures of the Theory of Planned Behaviour and measures of anxiety and shame. One month later, the same participants were recontacted and asked about their engagement in TSE in the previous month. RESULTS: Anticipated counterfactual relief and anticipated regret are independent, positive, predictors of intention to engage in TSE and, indirectly, TSE behaviour itself. Interestingly, anticipated temporal relief was negatively associated with intention to engage in TSE and, indirectly, behaviour. CONCLUSIONS: Our results suggest that it may be the counterfactual nature of anticipated regret and anticipated relief that underlies their positive association with TSE and other health-promoting behaviours. Interventions designed to increase engagement in preventive health behaviours, such as TSE, may benefit from the consideration of both positively and negatively valenced counterfactual emotions.

Children's limited tooling ability in a novel concurrent tool use task supports the innovation gap.

School-aged children have consistently shown a surprising developmental lag when attempting to innovate solutions to tool use tasks, despite being capable of learning to solve these problems from a demonstrator. We suggest that this "innovation gap" arises from tool tasks with more complex spatial relations. Following Fragaszy and Mangalam's new tooling theory, we predicted that innovating a new "sticker slide" task should be more challenging when two tools need to be used at the same time (concurrently) rather than one at a time (sequentially), despite the similarity of the other task elements. In line with previous work, both versions of the task were challenging for all ages of children (4-9 years) that we tested. However, the youngest group showed particularly extreme difficulties, which was marked by not a single child innovating the concurrent version. Although success significantly increased with age, even the oldest group failed to reach 50% success on the concurrent version of the task, whereas the majority of the two older groups could solve the sequential version. Thus, in this first study of concurrent tool use in children, we found support for the prediction that increasing the complexity of spatial relations in tooling exacerbates the innovation gap.

Cross-sectional analysis of healthcare worker mental health and utilisation of a digital mental health platform from 2020 to 2023.

BACKGROUND: Healthcare worker (HCW) anxiety and depression worsened during the pandemic, prompting the expansion of digital mental health platforms as potential solutions offering online assessments, access to resources and counselling. The use of these digital engagement tools may reflect tendencies and trends for the mental health needs of HCWs. OBJECTIVES: This retrospective, cross-sectional study investigated the association between the use of an online mental health platform within a large academic health system and measures of that system's COVID-19 burden during the first 3 years of the pandemic. METHODS: The study investigated the use of Cobalt, an online mental health platform, comprising deidentified mental health assessments and utilisation metrics. Cobalt, serves as an online mental health resource broadly available to health system employees, offering online evidence-based tools, coaching, therapy options and asynchronous content (podcasts, articles, videos and more). The analyses use validated mental health assessments (Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and post-traumatic stress disorder (PTSD)) alongside publicly available COVID-19 data. Statistical analyses employed univariate linear regression with Stata SE Statistical Software. RESULTS: Between March 2020 and March 2023, 43 308 independent user sessions were created on Cobalt, a majority being anonymous sessions (72%, n=31 151). Mental health assessments, including PHQ-4, PHQ-9, GAD-7 and primary care-PTSD, totalled 9462 over the time period. Risk for self-harm was noted in 17.1% of PHQ-9 assessments. Additionally, 4418 appointments were scheduled with mental health counsellors and clinicians. No significant associations were identified between COVID-19 case burden and Cobalt utilisation or assessment scores. CONCLUSION: Cobalt emerged as an important access point for assessing the collective mental health of the workforce, witnessing increased engagement over time. Notably, the study indicates the nuanced nature of HCW assessments of anxiety, depression and PTSD, with mental health scores reflecting moderate decreases in depression and anxiety but signalling potential increases in PTSD. Tailored resources are imperative, acknowledging varied mental health needs within the healthcare workforce. Ultimately, this investigation lays the groundwork for continued exploration of the impact and effectiveness of digital platforms in supporting HCW mental health.

The humanized platelet glycoprotein VI Fab inhibitor EMA601 protects from arterial thrombosis and ischaemic stroke in mice.

BACKGROUND AND AIMS: Glycoprotein VI (GPVI) is a platelet collagen/fibrin(ogen) receptor and an emerging pharmacological target for the treatment of thrombotic and thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017/glenzocimab, KD: 4.1 nM) recently passed a clinical phase 1b/2a study in patients with acute ischaemic stroke and was found to be well tolerated, safe, and potentially beneficial. In this study, a novel humanized anti-GPVI antibody Fab-fragment (EMA601; KD: 0.195 nM) was developed that inhibits hGPVI function with very high potency in vitro and in vivo. METHODS: Fab-fragments of the mouse anti-hGPVI IgG Emf6.1 were tested for functional GPVI inhibition in human platelets and in hGPVI expressing (hGP6tg/tg) mouse platelets. The in vivo effect of Emf6.1Fab was assessed in a tail bleeding assay, an arterial thrombosis model and the transient middle cerebral artery occlusion (tMCAO) model of ischaemic stroke. Using complementary-determining region grafting, a humanized version of Emf6.1Fab (EMA601) was generated. Emf6.1Fab/EMA601 interaction with hGPVI was mapped in array format and kinetics and quantified by bio-layer interferometry. RESULTS: Emf6.1Fab (KD: 0.427 nM) blocked GPVI function in human and hGP6tg/tg mouse platelets in multiple assays in vitro at concentrations ≥5 µg/mL. Emf6.1Fab (4 mg/kg)-treated hGP6tg/tg mice showed potent hGPVI inhibition ex vivo and were profoundly protected from arterial thrombosis as well as from cerebral infarct growth after tMCAO, whereas tail-bleeding times remained unaffected. Emf6.1Fab binds to a so far undescribed membrane proximal epitope in GPVI. The humanized variant EMA601 displayed further increased affinity for hGPVI (KD: 0.195 nM) and fully inhibited the receptor at 0.5 µg/mL, corresponding to a >50-fold potency compared with ACT017. CONCLUSIONS: EMA601 is a conceptually novel and promising anti-platelet agent to efficiently prevent or treat arterial thrombosis and thrombo-inflammatory pathologies in humans at risk.

A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology.

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The 'big five' personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses, including depression, anxiety and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Here, utilizing the Million Veteran Program cohort, we conducted a genome-wide association study in individuals of European and African ancestry. Adding other published data, we performed genome-wide association study meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 208, 14, 3, 2 and 7 independent genome-wide significant loci associated with neuroticism, extraversion, agreeableness, conscientiousness and openness, respectively. These findings represent 62 novel loci for neuroticism, as well as the first genome-wide significant loci discovered for agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety, while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

A Descriptive Exploration of Heart Rate Response to Live Professional Irish Dance Performance.

Introduction: Research investigating the physiological demands of dance performance has documented exercise intensity and time spent in work and rest; however, available data are across limited dance genres and often use rehearsal or simulated conditions. Real-time data recorded during live performance with an audience are limited. The aim of the study is to provide a detailed description of the physiological demands of live professional Irish dance performance. Method: The entire Irish dance cast of Riverdance participated in the study (n = 24). Approval was granted by the Institutional Research Ethics Committee. Matinee and evening performances on the first day of a tour were examined in a descriptive, cross-sectional design. Heart rate (HR) monitors worn discretely under costumes recorded data every 5-seconds. Video analysis allowed calculation of time spent in work and rest. All descriptive analyses were split by role (troupe/lead) and sex (male/female). Results: Dancers worked at hard/very hard intensities (mean > 72%, peak > 91% HRmax) for ~3 minutes at a time for 3-9 individual dance numbers. There was a high variation in overall demand experienced by individual dancers due to variation in both duration and intensity of on-stage time, dependent upon their role. Mean total on-stage time was 18.18 ± 5.82 minutes, 19.43 ± 5.80 minutes, 29.71 ± 0.62 minutes, 20.00 ± 0.00 minutes for male troupe, female troupe, male lead, and female lead dancers, respectively. Recovery periods were varied in terms of duration, activity undertaken, and HR response. Conclusion: Individual dance numbers within a professional Irish dance show were high intensity for a short duration when considered in isolation, but overall physiological demand experienced by any one dancer across the entire show varied dependent upon their role and off-stage/recovery practices. Future research investigating the physiological demands of dance performance should ensure analysis accounts for the individual dancer's role and should capture the entire show duration in repeated exposures.

Development of an evidence-based swimming representative military task to assess swimming competency in the British Army.

BACKGROUND: There is a requirement for British Army personnel to operate in/around water. Assessing role-related swimming/water competence will support personnel to conduct their job-roles safely and effectively. OBJECTIVE: To undertake a Job-Task Analysis (JTA) of British Army personnel when working in/around water and use this information to develop a Swimming Representative Military Task (RMT) to assess swimming/water competence. METHODS: Workshops, surveys, and observations were used to conduct a JTA, which identified and described job-tasks conducted by British Army personnel in/around water. Ergonomic analysis of these job-tasks identified seven water-based physical actions, which were considered fundamental for all personnel to be competent in performing. These seven actions guided design of a Swimming RMT, which was subsequently conducted twice by 103 serving personnel (89 men, 11 women) and once by 65 recruits (49 men, 16 women). RESULTS: The RMT comprised of entering the water in combat fatigues and webbing, removing webbing, swimming 50 m, and staying afloat for up to 10 minutes. During RMT trials, in trial 1, 85% of serving personnel and 74% of recruits successfully completed the RMT, which increased to 93% in serving personnel for trial 2. Across trials 1 and 2, all three timed RMT elements showed moderate-high correlational reliability (ICC range: 0.462-0.791). On average, serving personnel were quicker to complete the 50 m swim phase compared to recruits (91±24 s vs. 100±26 s; U = 2575.0, rb = -0.192, p = 0.039). CONCLUSIONS: The JTA-informed Swimming RMT provides an assessment of the minimum role-related swimming/water competence standard for British Army personnel.

Relieved or disappointed? Children's understanding of how others feel at the cessation of events.

People's emotional states are influenced not just by events occurring in the present but also by how events have unfolded in the past and how they are likely to unfold in the future. To what extent do young children understand the ways in which past events can affect current emotions even if they are no longer ongoing? In the current study, we explored children's ability to understand how others feel at the cessation of events-as events change from being present to being past. We asked 97 4- to 6-year-olds (40.2% female) and 35 adults (54.3% female) to judge how characters felt once particular types of events had ended relative to how they felt during these events. We found that from age 4, children judged (as adults do) that the character would feel positive at the cessation of negative events-what we refer to as temporal relief. This understanding of relief occurs earlier than has been shown in previous research. However, children were less likely than adults to judge others as feeling sad at the cessation of positive events-what we refer to as temporal disappointment. Overall, our findings suggest that children not only understand that the cessation of events can affect others' emotions but also recognize that people feel differently following the cessation of positive, negative, and neutral events.

A Switch from Glial to Neuronal Gene Expression Alterations in the Spinal Cord of SIV-infected Macaques on Antiretroviral Therapy.

Despite antiretroviral therapy (ART), HIV-associated peripheral neuropathy remains one of the most prevalent neurologic manifestations of HIV infection. The spinal cord is an essential component of sensory pathways, but spinal cord sampling and evaluation in people with HIV has been very limited, especially in those on ART. The SIV/macaque model allows for assessment of the spinal cord at key time points throughout infection with and without ART. In this study, RNA was isolated from the spinal cord of uninfected, SIV+, and SIV + ART animals to track alterations in gene expression using global RNA-seq. Next, the SeqSeek platform was used to map changes in gene expression to specific cell types. Pathway analysis of differentially expressed genes demonstrated that highly upregulated genes in SIV-infected spinal cord aligned with interferon and viral response pathways. Additionally, this upregulated gene set significantly overlapped with those expressed in myeloid-derived cells including microglia. Downregulated genes were involved in cholesterol and collagen biosynthesis, and TGF-b regulation of extracellular matrix. In contrast, enriched pathways identified in SIV + ART animals included neurotransmitter receptors and post synaptic signaling regulators, and transmission across chemical synapses. SeqSeek analysis showed that upregulated genes were primarily expressed by neurons rather than glia. These findings indicate that pathways activated in the spinal cord of SIV + ART macaques are predominantly involved in neuronal signaling rather than proinflammatory pathways. This study provides the basis for further evaluation of mechanisms of SIV infection + ART within the spinal cord with a focus on therapeutic interventions to maintain synaptodendritic homeostasis.

Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble GPV (sGPV) ectodomain was identified to spatiotemporally control fibrin formation through complex formation with thrombin. OBJECTIVES: We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. METHODS: We recruited 36 patients with ARDS in the wake of COVID-19 pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n = 23) vs ECMO (n = 13) compared with those of healthy controls. Patients were assessed at up to 3 time points (t1 = days 1-3; t2 = days 4-6; and t3 = days 7-14 after cannulation/study inclusion). RESULTS: Agonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and was associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO patients compared with that in non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and were associated with poor outcome. CONCLUSION: Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.

Characterization of heterogeneous skin constructs for full thickness skin regeneration in murine wound models.

An autologous heterogeneous skin construct (AHSC) has been developed and used clinically as an alternative to traditional skin grafting techniques for treatment of cutaneous defects. AHSC is manufactured from a small piece of healthy skin in a manner that preserves endogenous regenerative cellular populations. To date however, specific cellular and non-cellular contributions of AHSC to the epidermal and dermal layers of closed wounds have not been well characterized given limited clinical opportunity for graft biopsy following wound closure. To address this limitation, a three-part mouse full-thickness excisional wound model was developed for histologic and macroscopic graft tracing. First, fluorescent mouse-derived AHSC (mHSC) was allografted onto non-fluorescent recipient mice to enable macroscopic and histologic time course evaluation of wound closure. Next, mHSC-derived from haired pigmented mice was allografted onto gender- and major histocompatibility complex (MHC)-mismatched athymic nude mouse recipients. Resulting grafts were distinguished from recipient murine skin via immunohistochemistry. Finally, human-derived AHSC (hHSC) was xenografted onto athymic nude mice to evaluate engraftment and hHSC contribution to wound closure. Experiments demonstrated that mHSC and hHSC facilitated wound closure through production of viable, proliferative cellular material and promoted full-thickness skin regeneration, including hair follicles and glands in dermal compartments. This combined macroscopic and histologic approach to tracing AHSC-treated wounds from engraftment to closure enabled robust profiling of regenerated architecture and further understanding of processes underlying AHSC mechanism of action. These models may be applied to a variety of wound care investigations, including those requiring longitudinal assessments of healing and targeted identification of donor and recipient tissue contributions.

Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants.

SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.

Star-PCL shape memory polymer (SMP) scaffolds with tunable transition temperatures for enhanced utility.

Thermoresponsive shape memory polymers (SMPs) prepared from UV-curable poly(ε-caprolactone) (PCL) macromers have the potential to create self-fitting bone scaffolds, self-expanding vaginal stents, and other shape-shifting devices. To ensure tissue safety during deployment, the shape actuation temperature (i.e., the melt transition temperature or Tm of PCL) must be reduced from ∼55 °C that is observed for scaffolds prepared from linear-PCL-DA (Mn ∼ 10 kg mol-1). Moreover, increasing the rate of biodegradation would be advantageous, facilitating bone tissue healing and potentially eliminating the need for stent retrieval. Herein, a series of six UV-curable PCL macromers were prepared with linear or 4-arm star architectures and with Mns of 10, 7.5, and 5 kg mol-1, and subsequently fabricated into six porous scaffold compositions (10k, 7.5k, 5k, 10k★, 7.5k★, and 5k★) via solvent casting particulate leaching (SCPL). Scaffolds produced from star-PCL-tetraacrylate (star-PCL-TA) macromers produced pronounced reductions in Tm with decreased Mnversus those formed with the corresponding linear-PCL-diacrylate (linear-PCL-DA) macromers. Scaffolds were produced with the desired reduced Tm profiles: 37 °C < Tm < 55 °C (self-fitting bone scaffold), and Tm ≤ 37 °C (self-expanding stent). As macromer Mn decreased, crosslink density increased while % crystallinity decreased, particularly for scaffolds prepared from star-PCL-TA macromers. While shape memory behavior was retained and radial expansion pressure increased, this imparted a reduction in modulus but with an increase in the rate of degradation.

Beyond change scores: Employing an improved statistical approach to analyze the impact of entry fitness on physical performance during British Army basic training in men and women.

The aim was to use a robust statistical approach to examine whether physical fitness at entry influences performance changes between men and women undertaking British Army basic training (BT). Performance of 2 km run, seated medicine ball throw (MBT) and isometric mid-thigh pull (MTP) were assessed at entry and completion of Standard Entry (SE), Junior Entry-Short (JE-Short), and Junior Entry-Long (JE-Long) training for 2350 (272 women) recruits. Performance change was analyzed with entry performance as a covariate (ANCOVA), with an additional interaction term allowing different slopes for courses and genders (p < 0.05). Overall, BT courses saw average improvements in 2 km run performance (SE: -6.8% [-0.62 min], JE-Short: -4.6% [-0.43 min], JE-Long: -7.7% [-0.70 min]; all p < 0.001) and MBT (1.0-8.8% [0.04-0.34 m]; all p < 0.05) and MTP (4.5-26.9% [6.5-28.8 kg]; all p < 0.001). Regression models indicate an expected form of "regression to the mean" whereby test performance change was negatively associated with entry fitness in each course (those with low baseline fitness exhibit larger training improvements; all interaction effects: p < 0.001, η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ > 0.006), particularly for women. However, when matched for entry fitness, men displayed considerable improvements in all tests, relative to women. Training courses were effective in developing recruit physical fitness, whereby the level of improvement is, in large part, dependent on entry fitness. Factors including age, physical maturity, course length, and physical training, could also contribute to the variability in training response between genders and should be considered when analyzing and/or developing physical fitness in these cohorts for future success of military job-task performance.

C3 concentrations can be normal in patients with C3 glomerulopathy secondary to C3 nephritic factor.

C3 glomerulopathy (C3G) is a rare kidney disease caused by the glomerular deposition of C3 fragments secondary to alternative pathway complement dysregulation. C3 nephritic factors (C3Nef) are the most common acquired cause, and their detection has treatment and prognostic implications. Although C3 concentration can be normal in the presence of C3Nef, many laboratories will only perform C3Nef testing when C3 is low. We performed a retrospective study of all positive C3Nef results from the authors' laboratory since 2015 and found that two of the four patients with positive C3Nef and biopsy-confirmed C3G had normal C3 concentrations. This may be in part due to limitations in commercial C3 testing methods which use anti-C3c antisera directed against both C3 breakdown products and native C3. A normal C3 concentration should not preclude C3Nef testing in the appropriate clinical context.

A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology.

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The "Big Five" personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness, and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses including depression, anxiety, and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Utilizing the Million Veteran Program (MVP) cohort we conducted a genome-wide association study (GWAS) in individuals of European and African ancestry. Adding other published data, we performed GWAS meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 158, 14, 3, 2, and 7 independent genome-wide significant (GWS) loci associated with neuroticism, extraversion, agreeableness, conscientiousness, and openness, respectively. These findings represent 55 novel loci for neuroticism, as well as the first GWS loci discovered for extraversion and agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT, and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

Do both anticipated relief and anticipated regret predict decisions about influenza vaccination?

OBJECTIVE: Anticipated regret has been found to predict vaccination intentions and behaviours. We examined whether anticipated relief also predicts seasonal influenza vaccination intentions and behaviour. Given claims about differences in their antecedents and function, we distinguished between counterfactual relief (relief that a worse outcome did not obtain) and temporal relief (relief that an unpleasant experience is over). DESIGN: Cross-sectional. METHODS: Unvaccinated participants (N = 295) were recruited online in November 2020. Participants completed measures of anticipated regret, anticipated counterfactual relief, and anticipated temporal relief and measures of theory of planned behaviour constructs (attitudes, norms, perceived control, and intentions). One month later, the same participants were re-surveyed and asked to report their vaccination status. RESULTS: Although all anticipated emotion measures were associated with intentions and behaviour, only anticipated counterfactual relief and regret independently predicted vaccination intentions in regression analyses. Mediation analysis showed both anticipated counterfactual relief and regret were indirectly, via intentions, associated with behaviour. CONCLUSIONS: Results suggest that, regardless of valence, counterfactual emotions predict vaccination intention and, indirectly, behaviour. Furthermore, participants may differ in their sensitivity to the anticipation of positive versus negative counterfactual emotions. These findings may permit more precise targeting of interventions to increase vaccine uptake.

Blood Lactate and Heart Rate Responses Between Active and Passive Recovery Modes Over a 15-Minute Recovery Period in Female Dancers After Kathak Dance.

Introduction: Dance is physically demanding and results in blood lactate (BL) accumulation and elevated Heart Rate (HR). Researchers recommend using either Active Recovery (AR; eg, low-to-moderate intensity-exercise) or Passive Recovery (PR; eg, complete rest) modes after activity. We compared BL and HR responses between AR or PR over a 15-minute recovery period following a Kathak dance. Methods: Twelve female dancers (31.0 ± 6.0 years; 161.5 ± 4.9 cm; 55.5 ± 5.8 kg) performed 2 dance testing sessions (Day 1 = AR, Day 2 = PR) 48 hours apart. Each session started with a 10-minute warm up followed by dancers performing four 2-minute stages of Kathak dance, with three 1-minute periods between stages where we recorded HR and their Rate of Perceived Exertion (RPE:scale = 6-20) to match the intensity of both sessions. Post-dance, we recorded dancers' BL and HR at 1, 3, 5, 10, and 15 minutes while they recovered via AR or PR. Separate 2(mode) × (time) Repeated-Measures-ANOVA followed by simple-main-effects testing and adjusted Bonferroni-pairwise-comparisons examined differences in BL and HR responses across modes and time(α = .05). Results: Dancers' HR and RPE were similar across sessions. No mode × time interaction existed in BL (F4,8 = 3.6, P = .06). BL levels were similar across modes (F1,2 = 0.5, P = .5). BL levels reduced over time (F4,8 = 6.0, P = .02), but Bonferroni-comparisons did not reveal any pairwise differences. In HR a significant mode*time interaction (F4,36 = 11.0, P = .01, η2 = .55) was observed. Both Active and Passive recovery modes achieved absolute HR levels by 15 minutes, with PR mode stabilizing within 5 minutes. Conclusions: Over a 15-minute recovery period after Kathak dance, dancers' BL and HR responses were similar across time in both AR and PR, with HR being higher in AR. Dancers' HR remained similar from 1 to 3 minute post dance recovery and then dropped over time. Thus, dancers can rest up to 3 minutes and still maintain the same elevated HR. Overall, dancers can choose either AR or PR as their recovery mode based on their individual preferences.