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Identification of genetic variants associated with eating disorders is underway. The Anorexia Nervosa Genetics Initiative, an initiative of the Klarman Family Foundation, has contributed to advancing the field, yielding a large-scale genome-wide association study published in Nature Genetics. Eight genetic variants significantly associated with anorexia nervosa were identified, along with patterns of genetic correlations that suggest both psychiatric and metabolic origins of this serious and life-threatening illness. This article details the role of Professor Nick Martin in contributing to this important collaboration.
The present study evaluated the effects of low salinity on the early larval development of Oreochromis niloticus, specifically histological damage to white muscle, morphology of the yolk-sac surface and trunk area, and molecular expression of apoptosis and cell proliferation biomarkers. Newly hatched larvae were submitted to four salinity treatments for a period of 48 or 72 h, in duplicate: (S0) freshwater, (S2) 2 g l−1, (S4) 4 g l−1, and (S6) 6 g l−1NaCl. Larval development was examined using histology, electron microscopy, enzyme-linked immunosorbent assay (ELISA), and morphometry. At the yolk-sac surface, larvae of S4 and S6 displayed alterations to the apical opening of chloride cells that may be related to osmotic expenditure caused by the increased salinity. Caspase-3 expression did not differ significantly among treatments, however significantly lower proliferating cell nuclear antigen (PCNA) expression (P < 0.05) suggested minor cell proliferation in larvae of S4 and S6 compared with S0 and S2. Furthermore, there was a significant reduction in both trunk area and percentage of normal white muscle fibres (WF) in larvae of S4 and S6. Vacuolated areas and myofibrils concentrated at the cell periphery and found in the white muscle from larvae exposed to saline environments suggested disturbance to muscle development. Oedema and mononuclear infiltrate were also observed in the white muscle of S4 and S6 larvae. Together these results indicated that treatments with 4 and 6 g l−1 NaCl may cause osmoregulation expenditure, morphological alterations to the yolk-sac surface and histological damage to skeletal muscle that negatively affected the early larval development of O. niloticus.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
Ice algae are a key component in polar marine food webs and have an active role in large-scale biogeochemical cycles. They remain extremely under-sampled due to the coarse nature of traditional point sampling methods compounded by the general logistical limitations of surveying in polar regions. This study provides a first assessment of hyperspectral imaging as an under-ice remote-sensing method to capture sea-ice algae biomass spatial variability at the ice/water interface. Ice-algal cultures were inoculated in a unique inverted sea-ice simulation tank at increasing concentrations over designated cylinder enclosures and sparsely across the ice/water interface. Hyperspectral images of the sea ice were acquired with a pushbroom sensor attaining 0.9 mm square pixel spatial resolution for three different spectral resolutions (1.7, 3.4, 6.7 nm). Image analysis revealed biomass distribution matching the inoculated chlorophyll a concentrations within each cylinder. While spectral resolutions >6 nm hindered biomass differentiation, 1.7 and 3.4 nm were able to resolve spatial variation in ice algal biomass implying a coherent sensor selection. The inverted ice tank provided a suitable sea-ice analogue platform for testing key parameters of the methodology. The results highlight the potential of hyperspectral imaging to capture sea-ice algal biomass variability at unprecedented scales in a non-invasive way.
In 2008 it became policy that all those on the care programme approach were assessed for sexual violence/abuse. The implementation of this policy was assessed 8 years on. The findings of a survey and data request to Health and Social Care Information Centre are disappointing. We argue that this important initiative needs to be reinvigorated.
Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months.
In species that aggregate for reproduction, the social and fitness costs of movement between groups frequently lead to restricted exchange between breeding areas. We report on four individual humpback whales identified in both the Cape Verde Islands and Guadeloupe; locations separated by an ocean basin and >4000 km. This rate of exchange is rarely encountered between such geographically discrete breeding areas. Two individuals returned to the area where they were originally identified. In contrast, no individuals from the Cape Verde Islands were resighted to the much larger sample from the Dominican Republic, though the migratory distances from the feeding areas are comparable between these areas. The social factors driving the stark difference between groups that is observed here are not clear. Effective conservation requires an understanding of the extent and pattern of movement between population units. The findings presented here suggest that there may well be more than one behaviourally distinct group within the West Indies. More broadly, they argue that considerable caution is warranted in assumptions made regarding the number, boundaries and status of population units based solely on spatial separation or proximity.
We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU).
Retrospective cohort study (2005–2012)
A large tertiary-care center
Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares
A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006–2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed.
Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(−); P=.003).
A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients.
The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry.
The IMproving Paediatric and Adult Congenital Treatment– registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the ‘core’ IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis.
During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types – isolated or in combination with other procedures – were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory.
The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.
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.
Older prisoners are the fastest growing group of prisoners in most countries. They have high rates of physical and psychiatric co-morbidity, compared to community dwelling older persons and also compared with other prisoner groups. Very high rates of mental illness have been found in remand (pre-trial) prisoners when compared with other prisoner groups; however to date there have been no studies examining older male and female remand prisoners.
A retrospective chart review was conducted of all remands, to a male and a female prison, over a six and half-year period. Demographic data were collected pertaining to psychiatric and medical diagnoses and seriousness of offending.
We found rising numbers of older prisoners amongst male remand prisoners. Older remand prisoners had very high rates of affective disorder and alcohol misuse. They had rates of psychotic illnesses and deliberate self-harm comparable to younger remand prisoners. High rates of vulnerability were found among older prisoners and older prisoners had a greater need for general medical and psychiatric services than younger prisoners. We also found comparable offending patterns with younger prisoners and high rates of sexual offending among the older male prisoner group.
Given the ageing population of many countries it is likely the numbers of older prisoners will continue to grow and given their high levels of both physical and psychiatric illness this will have implications for future service delivery.
Nilpenia rossi new genus new species, described here from the Ediacara Member (Rawnsley Quartzite, South Australia), provides evidence of a Precambrian macroscopic sessile sediment-dweller. Nilpenia, ranging up to 30 cm in diameter, consists of two zones, a complex central area surrounded by radiating, dichotomously branching structures that decrease in diameter from the center to the outer edges. Other elements of the Ediacara Biota are interpreted to have been mat-encrusters but Nilpenia uniquely grew within the upper millimeters of the actual sediment displacing sediment with growth. This sediment surface was rippled and cohesive and may well have included an endobenthic mat. The branching network on the upper surface of the organisms would have been in contact with the water. The phylogenetic relationships of the Ediacara biota are not well constrained and Nilpenia is no exception. However, the morphology and ecology of Nilpenia represent a novel growth strategy present in the Ediacaran and not common today.
Using photometry at just two wavelengths it is possible to fit a blackbody to the spectrum of infrared excess that is the signature of a debris disc. From this the location of the dust can be inferred. However, it is well known that dust in debris discs is not a perfect blackbody. By resolving debris discs we can find the actual location of the dust and compare this to that inferred from the blackbody fit. Using the Herschel Space Observatory we resolved many systems as part of the DEBRIS survey. Here we discuss a sample of 9 discs surrounding A stars and find that the discs are actually located between 1 and 2.5 times further from their star than predicted by blackbody fits to the spectral energy distribution (SED). The variation in this ratio is due to differences in stellar luminosities, location of the dust, size distribution and composition of the dust.
The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene–environment–development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene–environment analyses, of alcohol misuse and stressful life events, some significant gene–environment and gene–development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene–environment and gene–development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.