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Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
Intertidal biofilms are a diverse mixture of bacteria, algae as well as sporelings of macroalgae embedded in a polysaccharid matrix. As the primary colonisers of newly formed surfaces, biofilms undergo a succession of different microbe assemblage until the mature state is reached. A biofilm can act as primary producers and as such recycle nutrients in a habitat. It will influence macrobiota by providing a food source or sending out cues to settlers. Biofilms themselves will be controlled by these settlers. This interaction between bottom-up and top-down plays a crucial part for the functioning of the rocky shore ecosystems. However, the diversity of biolfilms as well as it nature to react quickly to environmental changes makes identification and quantification of the individual compounds a difficult task. Subsequently, the understanding of biofilms in general and intertidal, rocky shore microbe assemblages has always tied to techniques and methods available at the time of study. This chapter focusses on the techniques that have greatly contributed to increasing knowledge of biofilms and discusses their findings. Nonetheless, newly developed methods promise to further this knowledge of the ecological role of biofilms on rocky coastlines.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Infants with CHD often experience growth failure. Ensuring optimal growth before surgery is associated with improved outcomes and has emerged as a significant cause of parental stress. Parents have reported a perceived lack of accessible feeding information for infants with CHD. To address this gap, the aim of this study was to develop feeding information to better support parents.
Materials and methods:
A search for existing material on six electronic databases and an internet search for unpublished (grey) literature on feeding information for infants with CHD were carried out. Following the development of feeding information, semi-structured interview(s) with parents/health-care professionals were completed, focusing on whether the information was easy to understand, relevant, provided sufficient information around feeding/feeding difficulties, and whether there were any information gaps. Iterative changes were made to the information following each interview. The process was completed until thematic saturation was achieved.
A total of 23 unique articles were identified of which 5 studies were included. From the grey literature, four web pages were reviewed. A total of 22 parents and 25 health-care professionals were interviewed. All parents/health-care professionals felt that the feeding information developed provided sufficient information; however, many wanted information on how to introduce complementary food, particularly if weaning was delayed.
This study describes the development of feeding information for infants with CHD. From parent interviews, gaps identified focused on the introduction of complementary foods and uncertainty regarding the feeding journey beyond surgery.
Performing an extended Focused Assessment with Sonography in Trauma (eFAST) exam is common practice in the initial assessment of trauma patients. The objective of this study was to systematically review the published literature on diagnostic accuracy of all components of the eFAST exam.
We searched Medline and Embase from inception through October 2018, for diagnostic studies examining the sensitivity and specificity of the eFAST exam. After removal of duplicates, 767 records remained for screening, of which 119 underwent full text review. Meta-DiSc™ software was used to create pooled sensitivities and specificities for included studies. Study quality was assessed using the Quality in Prognostic Studies (QUADAS-2) tool.
Seventy-five studies representing 24,350 patients satisfied our selection criteria. Studies were published between 1989 and 2017. Pooled sensitivities and specificities were calculated for the detection of pneumothorax (69% and 99% respectively), pericardial effusion (91% and 94% respectively), and intra-abdominal free fluid (74% and 98% respectively). Sub-group analysis was completed for detection of intra-abdominal free fluid in hypotensive (sensitivity 74% and specificity 95%), adult normotensive (sensitivity 76% and specificity 98%) and pediatric patients (sensitivity 71% and specificity 95%).
Our systematic review and meta-analysis suggests that e-FAST is a useful bedside tool for ruling in pneumothorax, pericardial effusion, and intra-abdominal free fluid in the trauma setting. Its usefulness as a rule-out tool is not supported by these results.
This study tested whether the association between interparental conflict and adolescent externalizing symptoms was moderated by a polygenic composite indexing low dopamine activity (i.e., 7-repeat allele of DRD4; Val alleles of COMT; 10-repeat variants of DAT1) in a sample of seventh-grade adolescents (Mean age = 13.0 years) and their parents. Using a longitudinal, autoregressive design, observational assessments of interparental conflict at Wave 1 predicted increases in a multi-informant measurement of youth externalizing symptoms 2 years later at Wave 3 only for children who were high on the hypodopaminergic composite. Moderation was expressed in a “for better” or “for worse” form hypothesized by differential susceptibility theory. Thus, children high on the dopaminergic composite experienced more externalizing problems than their peers when faced with more destructive conflicts but also fewer externalizing problems when exposed to more constructive interparental conflicts. Mediated moderation findings indicated that adolescent reports of their emotional insecurity in the interparental relationship partially explained the greater genetic susceptibility experienced by these children. More specifically, the dopamine composite moderated the association between Wave 1 interparental conflict and emotional insecurity 1 year later at Wave 2 in the same “for better” or “for worse” pattern as externalizing symptoms. Adolescent insecurity at Wave 2, in turn, predicted their greater externalizing symptoms 1 year later at Wave 3. Post hoc analyses further revealed that the 7-repeat allele of the dopamine receptor D4 (DRD4) gene was the primary source of plasticity in the polygenic composite. Results are discussed as to how they advance process-oriented Gene x Environment models of emotion regulation.
This study examined the interplay between a polygenic composite and cortisol activity as moderators of the mediational pathway among family adversity, youth negative emotional reactivity to family conflict, and their psychological problems. The longitudinal design contained three annual measurement occasions with 279 adolescents (Mean age = 13.0 years) and their parents. Latent difference score analyses indicated that observational ratings of adversity in interparental and parent–child interactions at Wave 1 predicted increases in a multimethod, multi-informant assessment of youth negative emotional reactivity to family conflict from Waves 1 to 2. Changes in youth negative emotional reactivity, in turn, predicted increases in a multi-informant (i.e., parents, adolescent, and teacher) assessment of psychological problems from Waves 1 to 3. Consistent with differential susceptibility theory, the association between family adversity and negative emotional reactivity was stronger for adolescents who carried more sensitivity alleles in a polygenic composite consisting of 5-HTTLPR, DRD4 VNTR, and BDNF polymorphisms. Analyses of adolescent cortisol in the period surrounding a family disagreement task at Wave 1 revealed that overall cortisol output, rather than cortisol reactivity, served as an endophenotype of the polygenic composite. Overall cortisol output was specifically associated with polygenic plasticity and moderated the association between family adversity and youth negative emotional reactivity in the same for better or for worse manner as the genetic composite. Finally, moderator-mediated-moderation analyses indicated that the moderating role of the polygenic plasticity composite was mediated by the moderating role of adolescent cortisol output in the association between family adversity and their emotional reactivity.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
Collaborative care can support the treatment of depression in people with long-term conditions, but long-term benefits and costs are unknown.
To explore the long-term (24-month) effectiveness and cost-effectiveness of collaborative care in people with mental-physical multimorbidity.
A cluster randomised trial compared collaborative care (integrated physical and mental healthcare) with usual care for depression alongside diabetes and/or coronary heart disease. Depression symptoms were measured by the symptom checklist-depression scale (SCL-D13). The economic evaluation was from the perspective of the English National Health Service.
191 participants were allocated to collaborative care and 196 to usual care. At 24 months, the mean SCL-D13 score was 0.27 (95% CI, −0.48 to −0.06) lower in the collaborative care group alongside a gain of 0.14 (95% CI, 0.06-0.21) quality-adjusted life-years (QALYs). The cost per QALY gained was £13 069.
In the long term, collaborative care reduces depression and is potentially cost-effective at internationally accepted willingness-to-pay thresholds.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
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.
There is a well-established discrepancy between paleontological and molecular data regarding the timing of the origin and diversification of placental mammals. Molecular estimates place interordinal diversification dates in the Cretaceous, while no unambiguous crown placental fossils have been found prior to the end-Cretaceous mass extinction. Here, the completeness of the eutherian fossil record through geological time is evaluated to assess the suggestion that a poor fossil record is largely responsible for the difference in estimates of placental origins. The completeness of fossil specimens was measured using the character completeness metric, which quantifies the completeness of fossil taxa as the percentage of phylogenetic characters available to be scored for any given taxon. Our data set comprised 33 published cladistic matrices representing 445 genera, of which 333 were coded at the species level.
There was no significant difference in eutherian completeness across the Cretaceous/Paleogene (K/Pg) boundary. This suggests that the lack of placental mammal fossils in the Cretaceous is not due to a poor fossil record but more likely represents a genuine absence of placental mammals in the Cretaceous. This result supports the “explosive model” of early placental evolution, whereby placental mammals originated around the time of the K/Pg boundary and diversified soon after.
No correlation was found between the completeness pattern observed in this study and those of previous completeness studies on birds and sauropodomorph dinosaurs, suggesting that different factors affect the preservation of these groups. No correlations were found with various isotope proxy measures, but Akaike information criterion analysis found that eutherian character completeness metric scores were best explained by models involving the marine-carbonate strontium-isotope ratios (87Sr/86Sr), suggesting that tectonic activity might play a role in controlling the completeness of the eutherian fossil record.
This study tested a hypothesized cascade in which children's insecure representations of the interparental relationship increase their school problems by altering children's cortisol reactivity to stress and their executive functioning. Participants included 235 families. The first of five measurement occasions occurred when the children were in kindergarten (M age = 6 years), and they were followed through the transition to high school. The results indicated that children's histories of insecure representations of the interparental relationship during the early school years were associated with executive functioning difficulties in adolescence (M age = 14 years). This in turn predicted subsequent increases in school adjustment difficulties 1 year later. In addition, elevated cortisol reactivity to interadult conflict mediated the association between early histories of insecurity and subsequent executive function problems in adolescence.
One of the most notable currents in social, cultural and political historiography is the interrogation of the categories of 'elite' and 'popular' politics and their relationship to each other, as wellas the exploration of why and how different sorts of people engaged with politics and behaved politically. While such issues are timeless, they hold a special importance for a society experiencing rapid political and social change, like early modern England. No one has done more to define these agendas for early modern historians than John Walter. His work has been hugely influential, and at itsheart has been the analysis of the political agency of ordinary people. The essays in this volume engage with the central issues of Walter's work, ranging across the politics of poverty, dearth and household, popular political consciousness and practice more broadly, and religion and politics during the English revolution. This outstanding collection, bringing together some of the leading historians of this period with some of the field's rising stars, will appeal to anyone interested in the social, cultural and political history of early modern England or issues of popular political consciousness and behaviour more generally.
MICHAEL J. BRADDICK is professor of history at the University of Sheffield. PHIL WITHINGTON is professor of history at the University of Sheffield.
CONTRIBUTORS: Michael J. Braddick, J. C. Davis, Amanda Flather, Steve Hindle, Mark Knights, John Morrill, Alexandra Shepard, Paul Slack, Richard M. Smith, Clodagh Tait, Keith Thomas, Phil Withington, Andy Wood, Keith Wrightson.