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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.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
The Winkie Drill is an agile, commercially available rock coring system. The U.S. Ice Drilling Program has modified a Winkie Drill for subglacial rock and ice/rock interface coring, as well as drilling and coring access holes through ice. The original gasoline engine was replaced with an electric motor though the two-speed gear reducer and Unipress hand feed system were maintained. Using standard aluminum AW34 drill rod (for 33.5 mm diameter core), the system has a depth capability of 120 m. The drill uses forward fluid circulation in a closed loop system. The drilling fluid is Isopar K, selected for favorable properties in polar environment. When firn or snow is present at the drill site, casing with an inflatable packer can be deployed to contain the drill fluid. The Winkie Drill will operate from sea level to high altitudes and operation results in minimal environmental impact. The drill can be easily and quickly assembled and disassembled in the field by two people. All components can be transported by Twin Otter or helicopter to the field site.
The COVID-19 pandemic is exerting major pressures on society, health and social care services and science. Understanding the progression and current impact of the pandemic is fundamental to planning, management and mitigation of future impact on the population. Surveillance is the core function of any public health system, and a multi-component surveillance system for COVID-19 is essential to understand the burden across the different strata of any health system and the population. Many countries and public health bodies utilise ‘syndromic surveillance’ (using real-time, often non-specific symptom/preliminary diagnosis information collected during routine healthcare provision) to supplement public health surveillance programmes. The current COVID-19 pandemic has revealed a series of unprecedented challenges to syndromic surveillance including: the impact of media reporting during early stages of the pandemic; changes in healthcare-seeking behaviour resulting from government guidance on social distancing and accessing healthcare services; and changes in clinical coding and patient management systems. These have impacted on the presentation of syndromic outputs, with changes in denominators creating challenges for the interpretation of surveillance data. Monitoring changes in healthcare utilisation is key to interpreting COVID-19 surveillance data, which can then be used to better understand the impact of the pandemic on the population. Syndromic surveillance systems have had to adapt to encompass these changes, whilst also innovating by taking opportunities to work with data providers to establish new data feeds and develop new COVID-19 indicators. These developments are supporting the current public health response to COVID-19, and will also be instrumental in the continued and future fight against the disease.
OBJECTIVES/GOALS: Total hip replacement (THR) improves function for those with arthritis, but not all patients have equal access to this elective procedure. To better geographically target healthcare resources, we explored whether geographic socioeconomic disadvantage is associated with incidence of elective THR. METHODS/STUDY POPULATION: We performed a cross-sectional analysis of data in the state of Maryland from 2013-2019. We categorized 5-digit zipcodes into national quartiles of socioeconomic disadvantage using the Area Deprivation Index (ADI). For each zipcode, we calculated the THR incidence rate using Maryland Health Services Cost Review Commission (HSCRC) inpatient and outpatient data in those age 65 years and older. We included only elective THRs. We analyzed the association between a zipcode’s disadvantage quartile and THR incidence rate using multivariate linear regression, correcting for differences across zipcodes in gender, race, and ethnicity distributions, and distance to the nearest hospital performing THRs. RESULTS/ANTICIPATED RESULTS: We analyzed 414 zipcodes with overall average THR rate of 370.8 per 100,000 persons >65yo per year. Relative to zipcodes in the least socioeconomically disadvantaged quartile, those in the second-least disadvantaged had 82.2 fewer THRs per 100,000 persons >65yo per year, those in the second-most disadvantaged had 144.2 fewer, and those in the most disadvantaged had 207.4 fewer (all p65yo per year, those in the second-most disadvantaged had 136.2 fewer, and those in the most disadvantaged had 182.9 fewer (all p <.05). DISCUSSION/SIGNIFICANCE OF IMPACT: More socioeconomically disadvantaged areas have significantly lower rates of elective THR, independent of differences in demographics and hospital proximity. These findings show how disparities can affect access and outcomes, and should inform targeting of community-level education and intervention.
This chapter provides an overview of changes in the higher education environment that inform admissions and placement decisions. Various factors that must be considered when reconceptualizing current admission and placement practices are discussed. An expanded assessment framework based on two models – the multilevel design model and the complementarity model – are described. These models aim to better support diverse students’ learning by improving the connection between assessments and instruction once students are admitted to higher education institutions. Finally, the contributions of technological advancements, measurement of noncognitive skills, and innovations in task design are described.
We analyze individual white dwarfs in open clusters observed by Gaia. In particular, we determine ages when different model ingredients are used. We also explore fundamental properties of the white dwarfs, including temperature and mass, when using different filter combinations. Such tests are important to understanding any systematic effects when applying similar techniques to field stars.
We employ Pan-STARRS photometry, Gaia trigonometric parallaxes, modern stellar evolution and atmosphere models, and our Bayesian fitting approach to determine cooling and total ages for 159,238 white dwarfs. In many cases we are able to derive precise ages (better than 5%) for individual white dwarfs. These results are meant for broad use within the white dwarf and stellar astrophysics communities and we plan to make available on-line the posterior distributions for cooling age, total age, initial stellar mass, and other parameters.
Despite the global significance of the Leach’s Storm-petrel Hydrobates leucorhous colony on Baccalieu Island, Newfoundland and Labrador, Canada, the estimate of 3.36 million breeding pairs reported for 1984 by Sklepkovych and Montevecchi stands as the single published population estimate for the world’s largest colony. This study increases knowledge of this population by analysing data from additional independent surveys conducted in 1984 and 1985, and by updating the population status with a survey conducted in 2013. Population estimates were derived by extrapolating occupied burrow densities to the estimated occupied area of four main habitat types (heath, forest, grass and fern), which in turn were based on proportions of habitats observed in plots (1984 and 1985) or by using a Geographic Information System approach (2013). Based on these surveys, the Leach’s Storm-petrel breeding population size on Baccalieu Island was estimated at 5.12 ± 0.73 (SE) and 4.60 ± 0.42 (SE) million pairs in 1984 and 1985 respectively, representing estimates 37–51% greater than the original 1984 survey. While discrepancies among these estimates were largely driven by the way occupied areas were estimated, our study confirms that Baccalieu Island hosts the largest Leach’s Storm-petrel colony in the world. Results from the 2013 survey estimate the current breeding Leach’s Storm-petrel population at 1.95 ± 0.14 (SE) million pairs, representing a 42% decline over 29 years (-1.4% per year), relative to the original published estimate of 3.36 ± 0.12 (SE) million pairs. The most prominent change has occurred in the density of storm-petrel burrows found in forest habitat which dropped by 70% despite forest remaining the second most abundant habitat available to nesting storm-petrels on Baccalieu Island. The cause of this decline remains unknown and is likely multi-faceted. Future research focusing on demographic studies is required to understand what is driving the population decline of this internationally important colony.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
Norovirus is a predominant cause of infectious gastroenteritis in countries worldwide [1–5]. It accounts for approximately 50% of acute gastroenteritis (AGE) and >90% of viral gastroenteritis outbreaks [6, 7]. The incubation period ranges between 10 and 48 h and illness duration is generally 1–3 days with self-limiting symptoms; however, this duration is often longer (e.g. 4–6 days) in vulnerable populations such as hospital patients or young children [2, 8]. Symptomatic infection of norovirus presents as acute vomiting, diarrhoea, abdominal cramps and nausea, with severe vomiting and diarrhoea (non-bloody) being most common [2, 5, 9].
Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
Understanding the burden of respiratory pathogens on health care is key to improving public health emergency response and interventions. In temperate regions, there is a large seasonal rise in influenza and other respiratory pathogens. We have examined the associations between individual pathogens and reported respiratory tract infections to estimate attributable burden. We used multiple linear regression to model the relationship between doctor consultation data and laboratory samples from week 3 2011 until week 37 2015. We fitted separate models for consultation data with in-hours and out-of-hours doctor services, stratified by different age bands. The best fitting all ages models (R2 > 80%) for consultation data resulted in the greatest burden being associated with influenza followed by respiratory syncytial virus (RSV). For models of adult age bands, there were significant associations between consultation data and invasive Streptococcus pneumoniae. There were also smaller numbers of consultations significantly associated with rhinovirus, parainfluenza, and human metapneumovirus. We estimate that a general practice with 10 000 patients would have seen an additional 18 respiratory tract infection consultations per winter week of which six had influenza and four had RSV. Our results are important for the planning of health care services to minimise the impact of winter pressures.
• Respiratory pathogen incidence explains over 80% of seasonal variation in respiratory consultation data.
• Influenza and RSV are associated with the biggest seasonal rises in respiratory consultation counts.
• A third of consultation counts associated with respiratory pathogens were due to influenza.
OBJECTIVES/SPECIFIC AIMS: Epidemiologic data suggest that BV is sexually transmitted with male partners colonized or infected with the responsible organism(s). The objective of this study was to compare the genital microbiota of women with recurrent BV and their regular male sexual partner using 16S rRNA gene sequencing and quantitative PCR targeting BV-candidate bacteria (Gardnerella vaginalis, Atopobium vaginae, BVAB1-3, Sneathia, Leptotrichia, and Megasphaera type I). METHODS/STUDY POPULATION: Women with recurrent BV (≥3 prior episodes, including a current episode) and their regular male partner participating in a BV treatment trial and providing genital specimens (women: vaginal; men: urethral, coronal sulcus, urine) at enrollment were included. Male specimens for each participant were pooled. 250 bp 16S rRNA V4 region PCR amplicons were sequenced and analyzed using the QIIME pipeline. Taxonomy was assigned using the RDP Classifier against a modified Greengenes database with additional vaginal taxonomies added. An average relative abundance cutoff of 0.5% was used for analysis. qPCR was also performed for specific BV-candidate bacteria. Spearman correlation coefficients were used to investigate associations between all genital bacteria in addition to BV-candidate bacteria between partnerships. To determine positive associations between partnerships, the Wilcoxon signed-rank test was used. RESULTS/ANTICIPATED RESULTS: In total, 45 partnerships were included. Mean partnership age was 31.3 (SD=7.9), 91.1% partnerships were African-American. The majority of partnerships (70.0%) reported condomless sex during the past 3 months. Regarding 16S data, 37 genital bacteria had an average relative abundance of ≥0.5%. The average Spearman correlation across all 45 partnerships was 0.28 (SD=0.27) (median=0.27, minimum=−0.21, maximum=0.84). Overall, a positive association of all genital bacteria existed across the partnerships (p<0.0001). However, regarding specific BV-candidate bacteria, Spearman correlation tests for G. vaginalis, A. vaginae, Prevotella bivia, Megasphaera type I, BVAB1, and BVAB2 were nonsignificant. In contrast, Sneathia spp. were positively correlated between partnerships (r=0.37, p=0.01). With regards to qPCR results, RNA Cq analyses provided significant evidence for a linear association between male and females for only A. vaginae (r=0.52, p=0.006). DISCUSSION/SIGNIFICANCE OF IMPACT: In monogamous heterosexual couples in which the female has BV, the vaginal microbiota of women and the penile/urine microbiota of men were significantly correlated, particularly with regards to Sneathia spp. and A. vaginae, supporting the hypothesis that BV-associated bacteria are exchanged during sex.
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
Introduction: Approximately 50% of patients discharged from the Emergency Department (ED) after syncope have no cause found. Long-term outcomes among syncope patients are not well studied, to guide physicians regarding outpatient testing and follow-up. The objective of this study was to conduct a systematic review for long-term (one year) outcomes among ED patients with syncope. We aim to use the results of this review to guide us in prospective analysis of one year outcomes with our large database of syncope patients. Methods: We searched Cochrane Central Register of Controlled Trials, Medline and Medline in Process, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from the inception to June, 2017. We included studies that reported long-term outcomes among adult ED patients (16 years or older) with syncope. We excluded studies on pediatric patients, and studies that included syncope mimickers: pre-syncope, seizure, intoxication, loss of consciousness after head trauma. We also excluded case reports, letters to the editor and review articles. Outcomes included death, syncope recurrence requiring hospitalization, arrhythmias and procedural interventions for arrhythmias. We selected articles based on title and abstract review during phase-1 and conducted full article review during phase-2. Meta-analysis was performed by pooling the outcomes using random effects model (RevMan v.5.3; Cochrane Collaboration). Results: Initial literature search generated 2094 articles after duplicate removal. 50 articles remained after phase-1 (=0.85) and 16 articles were included in the systematic review after phase-2 (=0.86). The 16 included studies enrolled a total of 44,755 patients. Pooled analysis at 1-year follow-up showed the following outcomes: 7% mortality; 14% recurrence of syncope requiring hospitalization; one study reported that 0.6% of patients had a pacemaker inserted; and two studies reported 0.8 11.5% of patients suffered new arrhythmias. Conclusion: An important proportion of ED patients with syncope suffer outcomes at 1-year. Appropriate follow-up is needed to prevent long-term adverse outcomes. Further prospective research to identify patients at risk for long-term important cardiac outcomes and death is needed.
The “Stop the Bleed” campaign advocates for non-medical personnel to be trained in basic hemorrhage control. However, it is not clear what type of education or the duration of instruction needed to meet that requirement. The objective of this study was to determine the impact of a brief hemorrhage control educational curriculum on the willingness of laypersons to respond during a traumatic emergency.
This “Stop the Bleed” education initiative was conducted by the University of Texas Health San Antonio Office of the Medical Director (San Antonio, Texas USA) between September 2016 and March 2017. Individuals with formal medical certification were excluded from this analysis. Trainers used a pre-event questionnaire to assess participants knowledge and attitudes about tourniquets and responding to traumatic emergencies. Each training course included an individual evaluation of tourniquet placement, 20 minutes of didactic instruction on hemorrhage control techniques, and hands-on instruction with tourniquet application on both adult and child mannequins. The primary outcome in this study was the willingness to use a tourniquet in response to a traumatic medical emergency.
Of 236 participants, 218 met the eligibility criteria. When initially asked if they would use a tourniquet in real life, 64.2% (140/218) responded “Yes.” Following training, 95.6% (194/203) of participants responded that they would use a tourniquet in real life. When participants were asked about their comfort level with using a tourniquet in real life, there was a statistically significant improvement between their initial response and their response post training (2.5 versus 4.0, based on 5-point Likert scale; P<.001).
In this hemorrhage control education study, it was found that a short educational intervention can improve laypersons’ self-efficacy and reported willingness to use a tourniquet in an emergency. Identified barriers to act should be addressed when designing future hemorrhage control public health education campaigns. Community education should continue to be a priority of the “Stop the Bleed” campaign.
RossEM, RedmanTT, MappJG, BrownDJ, TanakaK, CooleyCW, KharodCU, WamplerDA. Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons’ Willingness to Respond During a Traumatic Medical Emergency. Prehosp Disaster Med. 2018;33(2):127–132.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.