To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Recently, the Health of the Nation Outcome Scales 65+ (HoNOS65+) were revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA).
All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested modifying or expanding the glossary examples for some scales (e.g. those measuring problems with relationships and problems with activities of daily living) to be more older adult-specific.
Experts agreed that the HoNOS OA measures important constructs. Training may need to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended.
Inequalities in health outcomes, and avoidable deaths, in people with intellectual disability has highlighted the need for improved training and education in Intellectual Disability and Autism. Simulation training facilitated by actors with intellectual disability has been shown to improve connection with people with intellectual disability (Attoe et al 2017). The aim of this project was to develop a simulation-based training course, focused on topics in mental health, intellectual disability and autism, to improve participant confidence in clinical knowledge and skills, as well as support leadership and professionalism training. Here we evaluate the impact of the training on participants’ confidence, and the longer-term effect on attitudes and working practice after attendance.
A novel simulation-based training course, directed at Specialty Trainees, was developed based on the Specialty Training in Learning Disability curriculum. The course was co-delivered by a person with intellectual disability. Participants who attended the simulation training completed general feedback, pre-course and post-course confidence questionnaires and attended a semi-structured group interview at 2 months. Questionnaire data weres analysed using descriptive and inferential statistics. Group interview data were analysed using open & axial coding, and thematic analysis of content. The project was approved by East London NHS Foundation Trust Governance and Ethics Committee for Studies and Evaluations.
Eight psychiatrists participated in the training and completed the pre-course and post-course questionnaires. Independent t-test found significant increase in confidence for all scores from pre-course (M = 6.54, SE0.24) to post-course (M = 7.81, SE = 0.36), t= –2.93 p = 0.01. This included ratings of confidence in knowledge in areas such as mental health legislation, and improved confidence in skills such as communication with families of people with intellectual disability and difficult conversations with senior supervisors. In follow-up interviews we elucidated themes of the importance of supported, structured training opportunities with people with intellectual disability, and the value of connection with peers and supervisors.
Simulation based training in psychiatry, co-delivered with actors with intellectual disability, was reported to be an engaging and enjoyable form of learning. The evaluation suggests such training is effective in increasing trainee confidence in knowledge and skills at the time of training as well as resulting in a lasting change in attitudes after the training. We recommend such training be further developed and delivered at both postgraduate and undergraduate level.
We describe here the early Spathian (Early Triassic) Paris Biota decapod fauna from the western USA basin. This fauna contains two taxa of Aegeridae (Dendobranchiata), namely Anisaeger longirostrus n. sp. and Aeger sp. that are the oldest known representatives of their family, thus extending its temporal range by 5 Myr back into the Early Triassic. This fauna also includes two representatives of Glypheida (Pleocyemata) with Litogaster turnbullensis and Pemphix krumenackeri n. sp., confirming for the former and extending for the latter the temporal ranges of their respective superfamilies back to the Early Triassic. Overall, the Paris Biota decapods are some of the oldest known representatives of Decapoda, filling in an important gap in the evolutionary history of this group, especially during the Triassic that marks the early diversification of this clade. Additionally, we compile and provide overviews for all known Triassic decapods, which leads to the revision of four species of Middle and Late Triassic Aegeridae, and to a revised family assignment of a Middle Triassic Glypheida. Based on this refined dataset, we also investigate decapod diversity throughout the Triassic. We show that the apparent increase in decapod taxonomic richness is probably driven by the heterogeneity of the fossil record and/or sampling effort, and that the decapod alpha diversity is actually relatively high as soon as the Early Triassic and remains rather stable throughout the Triassic.
Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.
We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.
Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).
Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.
The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated.
We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS.
There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71–0.73] to 0.80 [0.79–0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96–1.10] to 0.72 [0.67–0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes.
Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.
Healthcare facilities are a well-known high-risk environment for transmission of M. tuberculosis, the etiologic agent of tuberculosis (TB) disease. However, the link between M. tuberculosis transmission in healthcare facilities and its role in the general TB epidemic is unknown. We estimated the proportion of overall TB transmission in the general population attributable to healthcare facilities.
We combined data from a prospective, population-based molecular epidemiologic study with a universal electronic medical record (EMR) covering all healthcare facilities in Botswana to identify biologically plausible transmission events occurring at the healthcare facility. Patients with M. tuberculosis isolates of the same genotype visiting the same facility concurrently were considered an overlapping event. We then used TB diagnosis and treatment data to categorize overlapping events into biologically plausible definitions. We calculated the proportion of overall TB cases in the cohort that could be attributable to healthcare facilities.
In total, 1,881 participants had TB genotypic and EMR data suitable for analysis, resulting in 46,853 clinical encounters at 338 healthcare facilities. We identified 326 unique overlapping events involving 370 individual patients; 91 (5%) had biologic plausibility for transmission occurring at a healthcare facility. A sensitivity analysis estimated that 3%–8% of transmission may be attributable to healthcare facilities.
Although effective interventions are critical in reducing individual risk for healthcare workers and patients at healthcare facilities, our findings suggest that development of targeted interventions aimed at community transmission may have a larger impact in reducing TB.
OBJECTIVES/GOALS: The primary goals of this study are 1) expand our understanding of the neural circuitry influenced by the neuropeptide Neuromedin U (NMU) via its receptor Neuromedin U Receptor 2 (NMUR2), and 2) provide alternative top-down mechanisms for how NMU regulates high fat food intake and cocaine taking. METHODS/STUDY POPULATION: Immunohistochemistry (IHC) for NMUR2 and cell markers was performed on rat brain tissue containing the medial prefrontal cortex (mPFC). To identify the source of the presynaptic NMUR2, anterograde tracing from the paraventricular nucleus or dorsal raphe nucleus to the mPFC utilizing an AAV2- dsRed-synaptobrevin fusion protein were performed (n=3) and will be followed by IHC. Using in vivo calcium imaging technology (InScopix nVista), neuronal activity (calcium transients) was recorded from the mPFC of two awake, freely behaving rats. Each animal underwent a single session of 30 minutes baseline activity, intraperitoneal NMU administration, and 30 minutes of post-treatment activity. Activity was then processed and recorded as distinct events using the InScopix data acquisition software. RESULTS/ANTICIPATED RESULTS: Medial prefrontal cortex staining for NMUR2 revealed a characteristic “beads on a string” motif, consistent with presynaptic receptor expression. Furthermore, we expect the anterograde tracing experiment will show colocalization of the dsRed-synaptobrevin fusion protein with NMUR2 on synaptic inputs into the medial prefrontal cortex. Following quantification of pre- and post- treatment events using the InScopix data acquisition software, total events during the pre- and post-treatment time periods were calculated. In these studies, both animals demonstrated a clear increase in calcium transient activity between pre- and post- treatment evaluations, suggesting that NMU administration increases the neuronal activity of neurons in the prefrontal cortex. DISCUSSION/SIGNIFICANCE: This research provides a new site of action for the known therapeutic effects of NMU. We demonstrate the presence of presynaptic NMUR2 in the mPFC and show that systemic administration of NMU increases mPFC neuronal activity. This illustrates NMU may act as a top-down mediator for substance use disorders and binge eating behaviors.
We describe the scientific goals and survey design of the First Large Absorption Survey in H i (FLASH), a wide field survey for 21-cm line absorption in neutral atomic hydrogen (H i) at intermediate cosmological redshifts. FLASH will be carried out with the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope and is planned to cover the sky south of
$\delta \approx +40\,\deg$
at frequencies between 711.5 and 999.5 MHz. At redshifts between
$z = 0.4$
(look-back times of 4 – 8 Gyr), the H i content of the Universe has been poorly explored due to the difficulty of carrying out radio surveys for faint 21-cm line emission and, at ultra-violet wavelengths, space-borne searches for Damped Lyman-
absorption in quasar spectra. The ASKAP wide field of view and large spectral bandwidth, in combination with a radio-quiet site, will enable a search for absorption lines in the radio spectra of bright continuum sources over 80% of the sky. This survey is expected to detect at least several hundred intervening 21-cm absorbers and will produce an H i-absorption-selected catalogue of galaxies rich in cool, star-forming gas, some of which may be concealed from optical surveys. Likewise, at least several hundred associated 21-cm absorbers are expected to be detected within the host galaxies of radio sources at
$0.4 < z < 1.0$
, providing valuable kinematical information for models of gas accretion and jet-driven feedback in radio-loud active galactic nuclei. FLASH will also detect OH 18-cm absorbers in diffuse molecular gas, megamaser OH emission, radio recombination lines, and stacked H i emission.
It is suggested that the different psychological vulnerability factors of intolerance of uncertainty (IU), anxiety sensitivity (AS) and distress tolerance (DT) may be in important in hoarding disorder (HD). However, the extent to which these factors are specific to HD compared with other disorders remains unclear.
The current study aimed to investigate differences in IU, AS and DT in three groups: HD (n=66), obsessive compulsive disorder (OCD; n=59) and healthy controls (HCs; n=63).
Participants completed an online battery of standardised self-report measures to establish the independent variable of group membership (HD, OCD and HC) and the dependent variables (IU, AS and DT).
A MANOVA analysis indicated statistically significant differences in IU, AS and DT between the clinical groups and HCs. Follow-up analyses showed no statistically significant differences between the HD and OCD group for any of the three constructs. The results remained the same when examining the effects of co-morbid HD and OCD. An unexpected finding was the trend for IU, AS and DT to be more severe when HD and OCD were co-morbid.
The evidence suggests the absence of a specific relationship between IU, AS or DT in HD and instead is consistent with existing research which suggests that these psychological vulnerability factors are transdiagnostic constructs across anxiety disorders. The implications of the findings are discussed.
The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use.
Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%.
In each survey, 28−47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%−37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%−41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%−40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60).
The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.
Using physiological markers to detect patients at risk of deterioration is common. Deaths at music festivals in Australia prompted scrutiny of tools to identify critically unwell patients for transport to hospital. This study evaluated initial physiological parameters to identify patients selected for transport to hospital from a music festival.
A retrospective audit of 2045 presentations at music festivals in Victoria, Australia, was performed. Presentation heart rate, systolic blood pressure, respiratory rate, oxygen saturation, temperature, and Glasgow Coma Scale were assessed using area under the receiver operating characteristic curve (AUROC) analysis, with a prespecified threshold of 0.7.
The only measured variable to exceed the prespecified cutpoint was initial systolic blood pressure, with an AUROC of 0.72 and optimal cutpoint of 122 mmHg. Using commonly accepted cutpoints for variables did not improve detection performance to acceptable levels, nor did using combination systems of cutpoints.
Initial physiological variables are poor predictors of the decision to transport to hospital from music festivals. Systolic blood pressure was significant, but only at a clinically insignificant value. Decisions on which patients to transport from an event site should incorporate more information than initial physiology. Senior clinicians should lead decision-making about hospital transport from music festivals.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.
Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.
Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.
HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.
Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.
Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).
In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.
Experimental studies of the influence of fluid–structure interaction on cloud cavitation about a stiff stainless steel (SS) and a flexible composite (CF) hydrofoil have been presented in Parts I (Smith et al., J. Fluid Mech., vol. 896, 2020a, p. A1) and II (Smith et al., J. Fluid Mech., vol. 897, 2020b, p. A28). This work further analyses the data and complements the measurements with reduced-order model predictions to explain the complex response. A two degrees-of-freedom steady-state model is used to explain why the tip bending and twisting deformations are much higher for the CF hydrofoil, while the hydrodynamic load coefficients are very similar. A one degree-of-freedom dynamic model, which considers the spanwise bending deflection only, is used to capture the dynamic response of both hydrofoils. Peaks in the frequency response spectrum are observed at the re-entrant jet-driven and shock-wave-driven cavity shedding frequencies, system bending frequency and heterodyne frequencies caused by the mixing of the two cavity shedding frequencies. The predictions capture the increase of the mean system bending frequency and wider bandwidth of frequency modulation with decreasing cavitation number. The results show that, in general, the amplitude of the deformation fluctuation is higher, but the amplitude of the load fluctuation is lower for the CF hydrofoil compared with the SS hydrofoil. Significant dynamic load amplification is observed at subharmonic lock-in when the shock-wave-driven cavity shedding frequency matches with the nearest subharmonic of the system bending frequency of the CF hydrofoil. Both measurements and predictions show an absence of dynamic load amplification at primary lock-in because of the low intensity of cavity load fluctuations with high cavitation number.
Dementia is a growing concern in Canada, affecting peoples’ health and raising the cost of care. Between June and October 2019, we conducted an environmental scan to identify primary care models, strategies, and resources for dementia care from 11 pre-selected countries and assess their impact on quality-of-life measures. Search strategies included a rapid scoping review, grey literature search, and discussions with stakeholders. Eighteen primary care-based models of dementia care were identified. Common factors include team-based care, centralized care/case coordination, individual treatment plans, a stepped-care approach, and support for care partners. Five provinces had released a dementia strategy. Evidence of positive outcomes supported primary care-based models for dementia care, although only one model demonstrated evidence of impact on quality of life. Although these findings are encouraging, further research is needed to identify primary care-based models of dementia care that demonstrably improve quality of life for people living with dementia and their care partners.
A global ageing population presents opportunities and challenges to designing urban environments that support ageing in place. The World Health Organization's Global Age-Friendly Cities movement has identified the need to develop communities that optimise health, participation and security in order to enhance quality of life as people age. Ensuring that age-friendly urban environments create the conditions for active ageing requires cities and communities to support older adults’ rights to access and move around the city (‘appropriation’) and for them to be actively involved in the transformation (‘making and remaking’) of the city. These opportunities raise important questions: What are older adults’ everyday experiences in exercising their rights to the city? What are the challenges and opportunities in supporting a rights to the city approach? How can the delivery of age-friendly cities support rights to the city for older adults? This paper aims to respond to these questions by examining the lived experiences of older adults across three cities and nine neighbourhoods in the United Kingdom. Drawing on 104 semi-structured interviews with older adults between the ages of 51 and 94, the discussion centres on the themes of: right to use urban space; respect and visibility; and the right to participate in planning and decision-making. These themes are illustrated as areas in which older adults’ rights to access and shape urban environments need to be addressed, along with recommendations for age-friendly cities that support a rights-based approach.
No established risk prediction tool exists in United Kingdom and Irish Paediatric Cardiology practice for patients undergoing cardiac catheterisation. The Catheterisation RISk score for Paediatrics is used primarily in North American practice to assess risk prior to cardiac catheterisation. Validating the utility and transferability of such a tool in practice provides the opportunity to employ an already established risk assessment tool in everyday practice.
To ascertain whether the Catheterisation RISk score for Paediatrics assessment tool can accurately predict complications within United Kingdom and Irish congenital catheterisation practice.
Clinical and procedural data including National Institute for Cardiovascular Outcomes Research derived outcome data from 1500 patients across five large congenital cardiology centres in the United Kingdom and Ireland were retrospectively collected. Catheterisation RISk score for Paediatrics were then calculated for each case and compared with the observed procedural outcomes. Chi-square analysis was used to determine the relationship between observed and predicted events.
Ninety-eight (6.6%) patients in this study experienced a significant complication as qualified by National Institute for Cardiovascular Outcomes Research classification. 4% experienced a moderate complication, 2.3% experienced a major complication and 0.3% experienced a catastrophic complication resulting in death. Calculated Catheterisation RISk score for Paediatrics scores correlated well with all observed adverse events for paediatric patients across all CRISP categories. The association was also transferable to adult congenital heart disease patients in lower Catheterisation RISk score for Paediatrics categories (CRISP 1–3).
The Catheterisation RISk score for Paediatrics score accurately predicts significant complications in congenital catheterisation practice in the United Kingdom and Ireland. Our data validated the Catheterisation RISk score for Paediatrics assessment tool in five congenital centres using National Institute for Cardiovascular Outcomes Research-derived outcome data.
The mechanics underlying ice–skate friction remain uncertain despite over a century of study. In the 1930s, the theory of self-lubrication from frictional heat supplanted an earlier hypothesis that pressure melting governed skate friction. More recently, researchers have suggested that a layer of abraded wear particles or the presence of quasi-liquid molecular layers on the surface of ice could account for its slipperiness. Here, we assess the dominant hypotheses proposed to govern ice–skate friction and describe experiments conducted in an indoor skating rink aimed to provide observations to test these hypotheses. Our results indicate that the brittle failure of ice under rapid compression plays a strong role. Our observations did not confirm the presence of full-contact water films and are more consistent with the presence of lubricating ice-rich slurries at discontinuous high-pressure zones (HPZs). The presence of ice-rich slurries supporting skates through HPZs merges pressure-melting, abrasion and lubricating films as a unified hypothesis for why skates are so slippery across broad ranges of speeds, temperatures and normal loads. We suggest tribometer experiments to overcome the difficulties of investigating these processes during actual skating trials.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.