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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.
Refractory ventricular fibrillation encountered during cardiac arrest has a mortality rate of 97%.1 As per the advanced cardiac life support (ACLS) guidelines, the management algorithm of ventricular fibrillation consists of chest compressions, epinephrine, defibrillation, and anti-arrhythmics.2 There have been reports describing the use of the fast-acting selective β-blocker, esmolol, and dual-sequential defibrillation in the management of ventricular fibrillation that is refractory to standard ACLS. We present a case of a 24-year-old male who had an out-of-hospital cardiac arrest, with refractory ventricular fibrillation despite high-quality cardiopulmonary resuscitation (CPR) and ACLS management. Along with standard ACLS, triple-sequential defibrillation was used to achieve return of spontaneous circulation (ROSC) after 82 minutes of downtime. An electrocardiogram (ECG) after ROSC showed an ST-elevation myocardial infarction (MI), and the patient underwent angiography showing a 100% occlusion of his left anterior descending artery. Following management of his coronary artery disease, he was discharged from the hospital 16 days later and was neurologically intact.
The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The 14C/12C ratio of living organisms is largely determined by the 14C/12C ratio of consumed diet as well as by the atmospheric 14C concentration together with the body’s metabolic processes. The measured 14C content of living matter compared to the atmospheric radiocarbon level can provide invaluable information about developmental processes. Our aim was to determine the 14C content of ten different tissues of the human eye using the 14C bomb-pulse dating signature. The 14C content of the atmosphere, so called 14C “bomb-pulse” has labeled humanity offering an opportunity to determine these special formation, turnover and substitution courses in biology. The results allowed us to construct a 14C map of the bomb-peak labeled human eye. According to the anatomical location of the tissues, an unexpected picture emerged as in moving from the outer parts towards the inner parts of the eye, the 14C content of each tissue decreased. The data presented here are compatible with the view that the oldest parts of the eye are the sclera, the limbus and the cornea, in this order, and moving further inside, the youngest tissue of the eye is the retina.
Primary care physicians can play a key role in supporting patients after behavioural weight loss, though little is known about communication between patients and physicians during this time. Adults (n=139) in a behavioural weight loss trial (delivered outside of primary care) who attended a primary care appointment after an initial weight loss period were surveyed to assess weight-related communication at their most recent appointment. Most participants (78%) reported discussing weight with their physician. Participants who discussed weight, compared to those who did not, lost more weight, had higher blood pressure, and were more likely to be male. Most (89%) reported that their physician was supportive of their weight loss, but only a few participants (6.9%) reported that their physician gave feedback on medical parameters. Areas for improvement identified include physicians providing universal support for modest weight changes and providing interpretation of medical measurements that changed due to weight loss.
The pessimistic arguments May challenges depend on an anti-Kantian philosophical assumption. That assumption is that what I call philosophical optimists about moral reason are also committed to empirical optimism, or what May calls “optimistic rationalism.” I place May's book in the literature by explaining how that assumption is resisted by Christine Korsgaard, one of May's examples of a contemporary Kantian.
To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015.
For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated.
All age groups and both sexes.
In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively.
The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.
Science fiction was being written throughout the seventeenth and eighteenth centuries, but it underwent a rapid expansion of cultural dissemination and popularity at the end of the nineteenth and beginning of the twentieth century. This Element explores the ways this explosion in interest in 'scientific romance', that informs today's global science fiction culture, manifests the specific historical exigences of the revolutions in publishing and distribution technology. H. G. Wells, Jules Verne and other science fiction writers embody in their art the advances in material culture that mobilize, reproduce and distribute with new rapidity, determining the cultural logic of twentieth-century science fiction in the process.
Absorbed residue studies have been used in subsistence research for decades. Only more recently have the chemical methods employed been used to explore the consumption of ritual concoctions such as those including cacao, yaupon holly, and alcohol. In this article we use mass spectrometry to identify Datura residues in prehistoric contexts from western Mexico and the American Southeast. Datura is a genus of flowering plants that contain hallucinogenic alkaloids. Their use in both regions is known historically and still continues today. This study sampled 55 pottery vessels and 18 shell vessels using both a traditional burr method and a water-based sonicator sampling method. Datura residues were found in 13 pottery vessels and 14 shell vessels using both sampling approaches. These results demonstrate that it is possible to identify Datura residue in pottery and shell vessels and that the use of Datura extends back into prehistory in both regions. The form and decoration of pottery vessels with Datura residues show correlations with specific motifs and themes. Historically, shell vessels were used in the Southeast for the consumption of another ritual beverage, called the Black Drink. The presence of Datura shows that those vessels were used for other kinds of beverages as well.
Layered transition metal dichalcogenides (TMDs) have attracted interest due to their promise for future electronic and optoelectronic technologies. As one approaches the two-dimensional (2D) limit, thickness and local topology can greatly influence the macroscopic properties of a material. To understand the unique behavior of TMDs it is therefore important to identify the number of atomic layers and their stacking in a sample. The goal of this work is to extract the thickness and stacking sequence of TMDs directly by matching experimentally recorded high-angle annular dark-field scanning transmission electron microscope images and convergent-beam electron diffraction (CBED) patterns to quantum mechanical, multislice scattering simulations. Advantageously, CBED approaches do not require a resolved lattice in real space and are capable of neglecting the thickness contribution of amorphous surface layers. Here we demonstrate the crystal thickness can be determined from CBED in exfoliated 1T-TaS2 and 2H-MoS2 to within a single layer for ultrathin ≲9 layers and ±1 atomic layer (or better) in thicker specimens while also revealing information about stacking order—even when the crystal structure is unresolved in real space.
While research on conspiracy theories and those who believe them has recently undergone a renaissance, there still exists a great deal of uncertainty about the measurement of conspiratorial beliefs and orientations, and the consequences of a conspiratorial mindset for expressly political attitudes and behaviors. We first demonstrate, using data from the 2012 American National Election Study, that beliefs in a variety of specific conspiracy theories are simultaneously, but differentially, the product of both a general tendency toward conspiratorial thinking and left/right political orientations. Next, we employ unique data including a general measure of conspiratorial thinking to explore the predictors of specific conspiracy beliefs. We find that partisan and ideological self-identifications are more important than any other variable in predicting ‘birther’ beliefs, while conspiratorial thinking is most important in predicting conspiracy beliefs about the assassination of John F. Kennedy and the 9/11 terrorist attacks.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Choice experiments addressing outcome uncertainty (OU) typically reframe continuous probability densities for each risky outcome into two discrete categories, each with a single probability of occurrence. The implications of this simplification for welfare estimation are unknown. This article evaluates the convergent validity of willingness-to-pay (WTP) estimates from a more accurate multiple-outcome treatment of OU, compared to the two-outcome approach. Results for a case study of coastal flood adaptation in Connecticut, United States, suggest that higher-resolution OU treatments increase choice complexity but can provide additional information on risk preferences and WTP. This tradeoff highlights challenges facing the valuation of uncertain outcomes.
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.