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Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development.
Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores.
AAAE conditions were associated with significant increases in CBCL Total (β 2.49; CI 1.98–3.00), Externalizing (β 1.54; CI 1.05–2.03), and Internalizing (β 2.28; CI 1.80–2.76) scores. Infection conditions were also associated with increased Total (β 1.27; CI 0.77–1.78), Externalizing (β 1.18; CI 0.70–1.66), and Internalizing (β 0.76; CI 0.28–1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales.
MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Most research on the causes of women's underrepresentation examines one of two stages of the political pipeline: the development of nascent political ambition or specific aspects of the campaign and election process. In this article, we make a different kind of contribution. We build on the growing literature on gender, psychology, and representation to provide an analysis of what kinds of men and women make it through the political pipeline at each stage. This allows us to draw some conclusions about the ways in which the overall process is similar and different for women and men. Using surveys of the general U.S. population (N = 1,939) and elected municipal officials such as mayors and city councilors (N = 2,354) that measure the distribution of Big Five personality traits, we find that roughly the same types of men and women have nascent political ambition; there is just an intercept shift for sex. In contrast, male and female elected officials have different personality profiles. These differences do not reflect underlying distributions in the general population or the population of political aspirants. In short, our data suggest that socialization into political ambition is similar for men and women, but campaign and election processes are not.
Does media choice cause polarization, or merely reflect it? We investigate a critical aspect of this puzzle: How partisan media contribute to attitude polarization among different groups of media consumers. We implement a new experimental design, called the Preference-Incorporating Choice and Assignment (PICA) design, that incorporates both free choice and forced exposure. We estimate jointly the degree of polarization caused by selective exposure and the persuasive effect of partisan media. Our design also enables us to conduct sensitivity analyses accounting for discrepancies between stated preferences and actual choice, a potential source of bias ignored in previous studies using similar designs. We find that partisan media can polarize both its regular consumers and inadvertent audiences who would otherwise not consume it, but ideologically opposing media potentially also can ameliorate the existing polarization between consumers. Taken together, these results deepen our understanding of when and how media polarize individuals.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Core graduate-level seminars, in many ways, establish the “canon” literature for scholars entering a discipline. In the study of American Politics, the contents of this canon vary widely across departments and instructors, with important implications for the perspectives to which graduate students are exposed. At a basic level, the demographic characteristics of the authors whose work is assigned can have a major impact on the diversity (or lack of diversity) of viewpoints presented in these introductory courses. Using a unique dataset derived from a survey of core American Politics graduate seminars at highly-ranked universities, this project assesses the gender diversity of the authors whose research is currently taught—overall and within a comprehensive list of topics and subtopics. We also assess the “substantive representation” of women (and other underrepresented groups) within the American Politics canon by examining the frequency with which gender, racial, and other forms of identity politics are taught in these introductory courses.
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.
Functional modeling is an effective method of depicting products in the design process. Using this approach, product architecture, concept generation, and physical modeling all contribute to the design process to generate a result full of quality and functionality. The functional basis approach provides taxonomy of uniform vocabulary to produce function structures with consistent functions (verbs) and flows (nouns). Material and energy flows dominate function structures in the mechanical engineering domain with only a small percentage including signal flows. Research suggests that the signal flow gap is due to the requirement of “carrier” flows of either material or energy to transport the signals between functions. This research suggests that incorporating controls engineering methodologies may increase the number of signal flows in function structures. We show correlations between the functional modeling and controls engineering in four facets: schematic similarities, performance matching through flows, mathematical function creation using bond graphs, and isomorphic matching of the aforementioned characteristics allows for analogical solutions. Controls systems use block diagrams to represent the sequential steps of the system. These block diagrams parallel the function structures of engineering design. Performance metrics between the two domains can be complimentary when decomposed down to nondimensional engineering units. Mathematical functions of the actions in controls systems can resemble the functional basis functions with bond graphs by identifying characteristic behavior of the functions on the flows. Isomorphic matching, using the schematic diagrams, produces analogies based upon similar functionality and target performance metrics. These four similarities bridge the mechanical and electrical domains via the controls domain. We provide concepts and contextualization for the methodology using domain-agnostic examples. We conclude with suggestion of pathways forward for this preliminary research.
We agree with Lake and colleagues on their list of “key ingredients” for building human-like intelligence, including the idea that model-based reasoning is essential. However, we favor an approach that centers on one additional ingredient: autonomy. In particular, we aim toward agents that can both build and exploit their own internal models, with minimal human hand engineering. We believe an approach centered on autonomous learning has the greatest chance of success as we scale toward real-world complexity, tackling domains for which ready-made formal models are not available. Here, we survey several important examples of the progress that has been made toward building autonomous agents with human-like abilities, and highlight some outstanding challenges.
This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Programme. ANU WiFeS SuperNovA Programme is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph on the Australian National University 2.3-m telescope. The first and primary data release of this programme (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from 2012 July to 2015 August. These spectra have been made publicly available via the WISEREP supernova spectroscopy repository.
We analyse the ANU WiFeS SuperNovA Programme sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the Wide Field Spectrograph instrument. In some cases, we were able to use the integral-field nature of the Wide Field Spectrograph instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its ‘super-Chandrasekhar’ status and enables measurement of the sub-solar host metallicity at the SN site.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Hypoplastic left heart syndrome is the most expensive birth defect managed in the United States, with a 5-year survival rate below 70%. Increasing evidence suggests that hospital volumes are inversely associated with mortality for infants with single ventricles undergoing stage 1 surgical palliation. Our aim was to examine the relative effects of surgeon and institutional volumes on outcomes and resource utilisation for these children.
A retrospective study was conducted using the Pediatric Health Information System database to examine the effects of the number of procedures performed per surgeon and per centre on mortality, costs, and post-operative length of stay for infants undergoing Risk Adjustment for Congenital Heart Surgery risk category six operations at tertiary-care paediatric hospitals, from 1 January, 2004 to 31 December, 2013. Multivariable modelling was used, adjusting for patient and institutional characteristics. Gaussian kernel densities were constructed to show the relative distributions of the effects of individual institutions and surgeons, before and after adjusting for the number of cases performed.
A total of 2880 infants from 35 institutions met the inclusion criteria. Mortality was 15.0%. Median post-operative length of stay was 24 days (IQR 14–41). Median standardized inpatient hospital costs were $156,000 (IQR $108,000–$248,000) in 2013 dollars. In the multivariable analyses, higher institutional volume was inversely associated with mortality (p=0.001), post-operative length of stay (p=0.004), and costs (p=0.001). Surgeon volume was associated with none of the measured outcomes. Neither institutional nor surgeon volumes explained much of the wide variation in outcomes and resource utilization observed between institutions and between surgeons.
Increased institutional – but not surgeon – volumes are associated with reduced mortality, post-operative length of stay, and costs for infants undergoing stage 1 palliation.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.