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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.
Environmental DNA (eDNA) surveying has potential to become a powerful tool for sustainable parasite control. As trematode parasites require an intermediate snail host that is often aquatic or amphibious to fulfil their lifecycle, water-based eDNA analyses can be used to screen habitats for the presence of snail hosts and identify trematode infection risk areas. The aim of this study was to identify climatic and environmental factors associated with the detection of Galba truncatula eDNA. Fourteen potential G. truncatula habitats on two farms were surveyed over a 9-month period, with eDNA detected using a filter capture, extraction and PCR protocol with data analysed using a generalized estimation equation. The probability of detecting G. truncatula eDNA increased in habitats where snails were visually detected, as temperature increased, and as water pH decreased (P < 0.05). Rainfall was positively associated with eDNA detection in watercourse habitats on farm A, but negatively associated with eDNA detection in watercourse habitats on farm B (P < 0.001), which may be explained by differences in watercourse gradient. This study is the first to identify factors associated with trematode intermediate snail host eDNA detection. These factors should be considered in standardized protocols to evaluate the results of future eDNA surveys.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
We describe a case of delayed COVID-19 diagnosis due to unrecognized community transmission in Atlanta, Georgia in mid-February 2020. This case resulted in transmission of COVID-19 to three of the four healthcare workers present during a diagnostic bronchoscopy procedure where only procedural masks were worn.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
The National Institute of Health has mandated good clinical practice (GCP) training for all clinical research investigators and professionals. We developed a GCP game using the Kaizen-Education platform. The GCP Kaizen game was designed to help clinical research professionals immerse themselves into applying International Conference on Harmonization GCP (R2) guidelines in the clinical research setting through case-based questions.
Students were invited to participate in the GCP Kaizen game as part of their 100% online academic Masters during the Spring 2019 semester. The structure of the game consisted of 75 original multiple choice and 25 repeated questions stemming from fictitious vignettes that were distributed across 10 weeks. Each question presented a teachable rationale after the answers were submitted. At the end of the game, a satisfaction survey was issued to collect player satisfaction data on the game platform, content, experience as well as perceptions of GCP learning and future GCP concept application.
There were 71 total players who participated and answered at least one question. Of those, 53 (75%) answered all 100 questions. The game had a high Cronbach’s alpha, and item analyses provided information on question quality, thus assisting us in future quality edits before re-testing and wider dissemination.
The GCP Kaizen game provides an alternative method for mandated GCP training using principles of gamification. It proved to be a reliable and an effective educational method with high player satisfaction.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.
We examined the prevalence of mental disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status.
This is the third phase of a military cohort study (2014–2016; n = 8093). The sample was based on participants from previous phases (2004–2006 and 2007–2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009.
The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel.
The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond.
Declaration of interest:
All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists’ Lead for Military and Veterans’ Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.
Ischemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied.
This study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED).
A retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers.
Barriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (P<.001). There was no significant difference in the proportion of patients who were administered tPA between those with and without barriers to care (14.1% vs 19.2%; P=.159).
Barriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ.
LiT, CushmanJT, ShahMN, KellyAG, RichDQ, JonesCMC. Barriers to Providing Prehospital Care to Ischemic Stroke Patients: Predictors and Impact on Care. Prehosp Disaster Med.2018;33(5):501–507.
Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.
Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for ICV in older adults.
99 older adults underwent Magnetic Resonance Imaging (MRI). ICV was measured by Statistical Parametric Mapping 8 (SPM8) software or Functional MRI of the Brain Software Library (FSL) extraction with manual editing, typically considered the gold standard. Head circumferences were determined using standardized tape measurement. We examined estimated correlation coefficients between head circumference and the two MRI-based ICV measurements.
Head circumference and ICV by SPM8 were moderately correlated (overall r = 0.73, men r = 0.67, women r = 0.63). Head circumference and ICV by FSL were also moderately correlated (overall r = 0.69, men r = 0.63, women r = 0.49).
Head circumference measurement was strongly correlated with MRI-derived ICV. Our study presents a simple method to approximate ICV among older patients, which may prove useful as a surrogate for cognitive reserve in large scale epidemiologic studies of cognitive outcomes. This study also suggests the stability of head circumference correlation with ICV throughout the lifespan.
Termite species and functional groups differ among regions globally (the functional-diversity anomaly). Here we investigate whether similar differences in biomass and abundance of termites occur among continents. Biomass and abundance data were collected with standardized sampling in Cameroon, Malaysia and Peru. Data from Peru were original to this study, while data from Cameroon and Malaysia were compiled from other sources. Species density data were sampled using a standardized belt transect (100 × 2 m) while the biomass and abundance measurements were sampled using a standardized protocol based on 2 × 2-m quadrats. Biomass and abundance data confirmed patterns found for species density and thus the existence of the functional diversity anomaly: highest estimates for biomass and abundance were found in Cameroon (14.5 ± 7.90 g m−2 and 1234 ± 437 ind m−2) followed by Malaysia (0.719 ± 0.193 g m−2 and 327 ± 72 ind m−2) and then Peru (0.345 ± 0.103 g m−2 and 130 ± 39 ind m−2). The biomass and abundance for each functional group were significantly different across sites for most termite functional groups. Biogeographical distribution of lineages was the primary cause for the functional diversity anomaly with true soil-feeding termites dominating in Cameroon and the absence of fungus-growing termites from Peru. These findings are important as the biomass and abundance of functional groups may be linked to ecosystem processes. Although this study allowed for comparisons between data from different regions further comparable data are needed to enhance the understanding of the role of termites in ecosystem processes on a global scale.
Plant-parasitic nematodes cause considerable damage to global agriculture. The ability to parasitize plants is a derived character that appears to have independently emerged several times in the phylum Nematoda. Morphological convergence to feeding style has been observed, but whether this is emergent from molecular convergence is less obvious. To address this, we assess whether genomic signatures can be associated with plant parasitism by nematodes. In this review, we report genomic features and characteristics that appear to be common in plant-parasitic nematodes while absent or rare in animal parasites, predators or free-living species. Candidate horizontal acquisitions of parasitism genes have systematically been found in all plant-parasitic species investigated at the sequence level. Presence of peptides that mimic plant hormones also appears to be a trait of plant-parasitic species. Annotations of the few genomes of plant-parasitic nematodes available to date have revealed a set of apparently species-specific genes on every occasion. Effector genes, important for parasitism are frequently found among those species-specific genes, indicating poor overlap. Overall, nematodes appear to have developed convergent genomic solutions to adapt to plant parasitism.
It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.