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Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.
To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.
We used regression analyses to compare cortical thickness and surface area (total and across gyri) between 120 unaffected carriers of rare CNVs associated with schizophrenia and 16 670 participants without any pathogenic CNV. A measure of cortical thickness and surface area covariance across gyri was also compared between groups.
Carrier status was associated with reduced surface area (β = −0.020 mm2, P < 0.001) and less robustly with increased cortical thickness (β = 0.015 mm, P = 0.035), and with increased covariance in thickness (carriers z = 0.31 v. non-carriers z = 0.22, P < 0.0005). Associations were mainly present in frontal and parietal areas and driven by a limited number of rare risk alleles included in our analyses (mainly 15q11.2 deletion for surface area and 16p13.11 duplication for thickness covariance).
Results for surface area conformed with previous clinical findings, supporting surface area reductions as an indicator of genetic liability for schizophrenia. Results for cortical thickness, though, argued against its validity as a potential risk marker. Increased structural thickness covariance across gyri also appears related to risk for schizophrenia. The heterogeneity found across the effects of rare risk alleles suggests potential different neurobiological gateways into schizophrenia's phenotype.
Traumatic brain injuries (TBI) may lead to persistent depression symptoms. We conducted several pilot studies to examine the efficacy of mindfulness-based interventions to deal with this issue; all showed strong effect sizes. The logical next step was to conduct a randomized controlled trial (RCT).
We sought to determine the efficacy of mindfulness-based cognitive therapy for people with depression symptoms post-TBI (MBCT-TBI).
Using a multi-site RCT design, participants (mean age = 47) were randomized to intervention or control arms. Treatment participants received a group-based, 10-week intervention; control participants waited. Outcome measures, administered pre- and post-intervention, and after three months, included: Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-9 (PHQ-9), and Symptom Checklist-90-Revised (SCL-90-R). The Philadelphia Mindfulness Scale (PHLMS) captured present moment awareness and acceptance.
BDI-II scores decreased from 25.47 to 18.84 in treatment groups while they stayed relatively stable in control groups (respectively 27.13 to 25.00; p = .029). We did not find statistically significant differences on the PHQ-9 and SCL-90R post- treatment. However, after three months, all scores were statistically significantly lower than at baseline (ps < .01). Increases in mindfulness were associated with decreases in BDI-II scores (r = -.401, p = .025).
MBCT-TBI may alleviate depression symptoms up to three months post-intervention. Greater mindfulness may have contributed to the reduction in depression symptoms although the association does not confirm causality. More work is required to replicate these findings, identify subgroups that may better respond to the intervention, and refine the intervention to maximize its effectiveness.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
The north-west European population of Bewick’s Swan Cygnus columbianus bewickii declined by 38% between 1995 and 2010 and is listed as ‘Endangered’ on the European Red List of birds. Here, we combined information on food resources within the landscape with long-term data on swan numbers, habitat use, behaviour and two complementary measures of body condition, to examine whether changes in food type and availability have influenced the Bewick’s Swan’s use of their main wintering site in the UK, the Ouse Washes and surrounding fens. Maximum number of Bewick’s Swans rose from 620 in winter 1958/59 to a high of 7,491 in winter 2004/05, before falling to 1,073 birds in winter 2013/14. Between winters 1958/59 and 2014/15 the Ouse Washes supported between 0.5 and 37.9 % of the total population wintering in north-west Europe (mean ± 95 % CI = 18.1 ± 2.4 %). Swans fed on agricultural crops, shifting from post-harvest remains of root crops (e.g. sugar beet and potatoes) in November and December to winter-sown cereals (e.g. wheat) in January and February. Inter-annual variation in the area cultivated for these crops did not result in changes in the peak numbers of swans occurring on the Ouse Washes. Behavioural and body condition data indicated that food supplies on the Ouse Washes and surrounding fens remain adequate to allow the birds to gain and maintain good body condition throughout winter with no increase in foraging effort. Our findings suggest that the recent decline in numbers of Bewick’s Swans at this internationally important site was not linked to inadequate food resources.
Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.
The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour. Compared with controls, GS subjects had a favourable cardiovascular lipid profile – lower LDL (4·0 (sem 0·3) v. 2·8 (sem 0·2) mmol/l; P=0·008) and LDL:HDL ratio (3·2 (sem 0·4) v. 1·8 (sem 0·2); P=0·005) and modified haematological profile. The majority of the GS subjects followed a low-gluten lifestyle, which helps to reduce the gastrointestinal (GI) symptoms severity. The low-gluten lifestyle does not have any effect on the quality of life, fatigue or mental state of this population. Consumption of normal wheat bread increased GI symptoms in GS subjects compared with their habitual diet. ANPEP lowered the immunogenic gluten in the treated bread by approximately 40 %. However, when compared with the control bread for inducing GI symptoms, no treatment effects were apparent. ANPEP can be applied in the production of bread with taste, texture and appearance comparable with standard bread.
Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.
Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.
Euclid is a Europe-led cosmology space mission dedicated to a visible and near infrared survey of the entire extra-galactic sky. Its purpose is to deepen our knowledge of the dark content of our Universe. After an overview of the Euclid mission and science, this contribution describes how the community is getting organized to face the data analysis challenges, both in software development and in operational data processing matters. It ends with a more specific account of some of the main contributions of the Swiss Science Data Center (SDC-CH).
Little is known about the mental health of partners of survivors of high levels of trauma in post-conflict countries.
We studied 677 spouse dyads (n = 1354) drawn from a community survey (response 82.4%) in post-conflict Timor-Leste. We used culturally adapted measures of post-traumatic stress disorder (PTSD), psychological distress, explosive anger and grief.
Latent class analysis identified three classes of couples: class 1, comprising women with higher trauma events (TEs), men with intermediate TEs (19%); class 2, including men with higher TEs, women with lower TEs (23%); and class 3, comprising couples in which men and women had lower TE exposure (58%) (the reference group). Men and women partners of survivors of higher TE exposure (classes 1 and 2) had increased symptoms of explosive anger and grief compared with the reference class (class 3). Women partners of survivors of higher TE exposure (class 2) had a 20-fold increased rate of PTSD symptoms compared with the reference class, a pattern that was not evident for men living with women exposed to higher levels of trauma (class 1).
Men and women living with survivors of higher levels of trauma showed an increase in symptoms of grief and explosive anger. The manifold higher rate of PTSD symptoms amongst women living with men exposed to high levels of trauma requires replication. It is important to assess the mental health of partners when treating survivors of high levels of trauma in post-conflict settings.
We present new local groundwater-level rise data from two Late Glacial aeolian dunes, located near Barendrecht and Oud-Alblas in the western Rhine-Meuse delta. These data are based on AMS radiocarbon dating of terrestrial macrofossils, collected from the base of peat formed on the slopes of these dunes. This method avoids contamination of bulk peat samples by old soil carbon or younger rootlets and rhizomes, as well as the hardwater effect. The new data are used to assess the reliability of previously published groundwater-level index data based on conventional radiocarbon dating of bulk basal peat samples from the slopes of the Late Glacial aeolian dunes at Barendrecht, Hillegersberg, Bolnes and Wijngaarden, all located in the western Rhine-Meuse delta.
Comparison of the new and published groundwater-level data shows no significant systematic difference between conventionally dated bulk peat samples and AMS-dated samples of terrestrial macrofossils. The new data from the dune at Barendrecht confirm the reliability of the younger than 6600 cal yr BP age-depth data from the dunes at Hillegersberg and near Bolnes. This result supports the validity of this part of the mean sea-level (MSL) curve for the western Netherlands. Consequently, the position of the groundwater-level curve for Flevoland (central Netherlands) below this MSL curve can most likely be attributed to differential land-level movement.
The available data show that the groundwater-gradient effect in the western Rhine-Meuse delta became less than 5 cm/km after 6600 cal yr BP. Finally, temporal correlation between temporary increases in local groundwater-level rise with known shifts of river courses in the delta plain suggests, that avulsions can explain sudden local deviations from the trend in groundwater-level rise. A general conclusion of this study is that a complex relationship exists between sea level and local delta-plain water levels.
Increasing recognition of the extent to which nitrous oxide (N2O) contributes to climate change has resulted in greater demand to improve quantification of N2O emissions, identify emission sources and suggest mitigation options. Agriculture is by far the largest source and grasslands, occupying c. 0·22 of European agricultural land, are a major land-use within this sector. The application of mineral fertilizers to optimize pasture yields is a major source of N2O and with increasing pressure to increase agricultural productivity, options to quantify and reduce emissions whilst maintaining sufficient grassland for a given intensity of production are required. Identification of the source and extent of emissions will help to improve reporting in national inventories, with the most common approach using the IPCC emission factor (EF) default, where 0·01 of added nitrogen fertilizer is assumed to be emitted directly as N2O. The current experiment aimed to establish the suitability of applying this EF to fertilized Scottish grasslands and to identify variation in the EF depending on the application rate of ammonium nitrate (AN). Mitigation options to reduce N2O emissions were also investigated, including the use of urea fertilizer in place of AN, addition of a nitrification inhibitor dicyandiamide (DCD) and application of AN in smaller, more frequent doses. Nitrous oxide emissions were measured from a cut grassland in south-west Scotland from March 2011 to March 2012. Grass yield was also measured to establish the impact of mitigation options on grass production, along with soil and environmental variables to improve understanding of the controls on N2O emissions. A monotonic increase in annual cumulative N2O emissions was observed with increasing AN application rate. Emission factors ranging from 1·06–1·34% were measured for AN application rates between 80 and 320 kg N/ha, with a mean of 1·19%. A lack of any significant difference between these EFs indicates that use of a uniform EF is suitable over these application rates. The mean EF of 1·19% exceeds the IPCC default 1%, suggesting that use of the default value may underestimate emissions of AN-fertilizer-induced N2O loss from Scottish grasslands. The increase in emissions beyond an application rate of 320 kg N/ha produced an EF of 1·74%, significantly different to that from lower application rates and much greater than the 1% default. An EF of 0·89% for urea fertilizer and 0·59% for urea with DCD suggests that N2O quantification using the IPCC default EF will overestimate emissions for grasslands where these fertilizers are applied. Large rainfall shortly after fertilizer application appears to be the main trigger for N2O emissions, thus applicability of the 1% EF could vary and depend on the weather conditions at the time of fertilizer application.
Using semi-empirical isochrones, we find the age of the Taurus star-forming region to be 3-4 Myr. Comparing the disc fraction in Taurus to young massive clusters suggests discs survive longer in this low density environment. We also present a method of photometrically de-reddening young stars using iZJH data.
Undulatory locomotion is an archetypal mode of propulsion for natural swimmers across scales. Undulatory swimmers convert transverse body oscillations into forward velocity by a complex interplay between their flexural movements, morphological features and the fluid environment. Natural evolution has produced a wide range of morphokinematic examples of undulatory swimmers that often serve as inspiration for engineering devices. It is, however, unknown to what extent natural swimmers are optimized for hydrodynamic performance. In this work, we reverse-engineer the morphology and gait for fast and efficient swimmers by coupling an evolution strategy to three-dimensional direct numerical simulations of flows at intermediate Reynolds numbers. The fastest swimmer is slender with a narrow tail fin and performs a sequence of C-starts to maximize its average velocity. The most efficient swimmer combines moderate transverse movements with a voluminous head, tapering into a streamlined profile via a pronounced inflection point. These optimal solutions outperform anguilliform swimming zebrafish in both efficiency and speed. We investigate the transition between morphokinematic solutions in the speed–energy space, laying the foundations for the design of high-performance artificial swimming devices.