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The expensive-tissue hypothesis (ETH) posited a brain–gut trade-off to explain how humans evolved large, costly brains. Versions of the ETH interrogating gut or other body tissues have been tested in non-human animals, but not humans. We collected brain and body composition data in 70 South Asian women and used structural equation modelling with instrumental variables, an approach that handles threats to causal inference including measurement error, unmeasured confounding and reverse causality. We tested a negative, causal effect of the latent construct ‘nutritional investment in brain tissues’ (MRI-derived brain volumes) on the construct ‘nutritional investment in lean body tissues’ (organ volume and skeletal muscle). We also predicted a negative causal effect of the brain latent on fat mass. We found negative causal estimates for both brain and lean tissue (−0.41, 95% CI, −1.13, 0.23) and brain and fat (−0.56, 95% CI, −2.46, 2.28). These results, although inconclusive, are consistent with theory and prior evidence of the brain trading off with lean and fat tissues, and they are an important step in assessing empirical evidence for the ETH in humans. Analyses using larger datasets, genetic data and causal modelling are required to build on these findings and expand the evidence base.
This chapter covers the development of diagnostic tests that detect and often amplify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids (molecular tests) or directly detect protein antigens (antigen tests). In the Rapid Acceleration of Diagnostics (RADx®) Tech program, tests that could be performed by following the instructions for use (Clinical Laboratory Improvement Amendments-waived point-of-care tests) or at home (over the counter) became more ubiquitous and represented a paradigm shift in infectious disease diagnostics away from reference laboratory testing by trained laboratorians. Understanding the clinical use case and unmet need is essential to the development of successfully commercialized tests. Important considerations include sample type and collection, the timing of testing (asymptomatic, contact of a known case, or symptomatic), biosafety, the limit of detection and sensitivity, specificity, the turnaround time, form factor and workflow, internal controls, early verification and validation, and supply chain bottlenecks.
Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
The Inquisitions post mortem (IPMs) are a truly wonderful source for many different aspects of late medieval countryside and rural life. They have recently been made digitally accessible and interrogatable by the Mapping the Medieval Countryside project, and the first fruits of these developments are presented here. The chapters examine IPMs in connection with the landscape and topography of England, in particular markets and fairs and mills; and consider the utility of proofs of age for everyday life on such topics as the Church, retaining, and the wine trade.
Michael Hicks is Emeritus Professor of Medieval History at the University of Winchester.
Contributors: Katie A. Clarke, William S. Deller, Paul Dryburgh, Christopher Dyer, Janette Garrett, Michael Hicks, Matthew Holford, Gordon McKelvie, Stephen Mileson, Simon Payling, Matthew Tompkins, Jennifer Ward.
Migrant youths endure many challenges. Such challenges can be stressful and lead to psychological difficulties. We investigated the relationship between migration, psychopathology and stressful events in children and adolescents. We hypothesised that migrant youths would show higher levels of psychopathology and more stressful life events than non-migrant youths.
Method
Using the Child cohort (Cohort ‘98) of the ‘Growing up in Ireland’ study we investigated psychopathology, as measured by the Strengths and Difficulties questionnaire (SDQ) at age 9 and 13 and stressful life events in migrant and non-migrant youths.
Results
There was no significant difference between the proportion of migrant and non-migrant youths reporting psychopathology in childhood (p>0.05) or adolescence (p>0.05). Analysis of the SDQ subscales revealed that a significantly greater proportion of migrant youths had hyperactivity problems in childhood (p = 0.04) but a greater proportion of non-migrant youths had emotional problems in early adolescence (p = 0.04). We found that migrant youths experienced significantly more stressful life events than their non-migrant counterparts (p<0.01), however, once ‘Moving house/country‘ was removed as a stressor, there was no difference between the groups (p>0.27).
Conclusions
Contrary to our hypothesis, we observed that there were few differences between migrant and non-migrant youths in the levels of psychopathology. Migrant youths experienced a greater number of stressful life events, however, this was attributable to stressors relating to moving. An increased understanding of the factors promoting resilience, as demonstrated by the migrant youths, could aid health professionals and policy makers to effectively tailor interventions for mental health promotion.
The development of algorithms for agile science and autonomous exploration has been pursued in contexts ranging from spacecraft to planetary rovers to unmanned aerial vehicles to autonomous underwater vehicles. In situations where time, mission resources and communications are limited and the future state of the operating environment is unknown, the capability of a vehicle to dynamically respond to changing circumstances without human guidance can substantially improve science return. Such capabilities are difficult to achieve in practice, however, because they require intelligent reasoning to utilize limited resources in an inherently uncertain environment. Here we discuss the development, characterization and field performance of two algorithms for autonomously collecting water samples on VALKYRIE (Very deep Autonomous Laser-powered Kilowatt-class Yo-yoing Robotic Ice Explorer), a glacier-penetrating cryobot deployed to the Matanuska Glacier, Alaska (Mission Control location: 61°42′09.3″N 147°37′23.2″W). We show performance on par with human performance across a wide range of mission morphologies using simulated mission data, and demonstrate the effectiveness of the algorithms at autonomously collecting samples with high relative cell concentration during field operation. The development of such algorithms will help enable autonomous science operations in environments where constant real-time human supervision is impractical, such as penetration of ice sheets on Earth and high-priority planetary science targets like Europa.
There is consensus about the importance of ‘recovery’ in mental health services, but the link between recovery orientation of mental health teams and personal recovery of individuals has been underresearched.
Aims
To investigate differences in team leader, clinician and service user perspectives of recovery orientation of community adult mental health teams in England.
Method
In six English mental health National Health Service (NHS) trusts, randomly chosen community adult mental health teams were surveyed. A random sample of ten patients, one team leader and a convenience sample of five clinicians were surveyed from each team. All respondents rated the recovery orientation of their team using parallel versions of the Recovery Self Assessment (RSA). In addition, service users also rated their own personal recovery using the Questionnaire about Processes of Recovery (QPR).
Results
Team leaders (n = 22) rated recovery orientation higher than clinicians (n = 109) or patients (n = 120) (Wald(2) = 7.0, P = 0.03), and both NHS trust and team type influenced RSA ratings. Patient-rated recovery orientation was a predictor of personal recovery (b = 0.58, 95% CI 0.31–0.85, P<0.001). Team leaders and clinicians with experience of mental illness (39%) or supporting a family member or friend with mental illness (76%) did not differ in their RSA ratings from other team leaders or clinicians.
Conclusions
Compared with team leaders, frontline clinicians and service users have less positive views on recovery orientation. Increasing recovery orientation may support personal recovery.
The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.