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Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
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.
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.
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.
Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.
We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.
Current subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.
This editorial proposes a shift in emphasis in the field of mental health epidemiology in conflict-affected settings. After a brief summary of the nature of contemporary armed conflicts, we consider the current and potential roles that epidemiology can play with regard to: (1) establishing the burden of mental disorders; (2) identifying risk and protective factors; and (3) intervention research. We advocate for improved methodological rigor; more attention to mixed methods approaches and multi-level longitudinal research; inclusion of the determinants of mental health beyond conflict-related violence; and consideration of a wider array of mental health outcomes. We particularly highlight the importance of expanding interest to epidemiological research that advances prevention and promotion interventions (e.g., in the early childhood period), in order to fill the gap between epidemiology and mental health practice in conflict-affected settings.
Intercropping systems that include legumes can provide symbiotically fixed nitrogen (N) and potentially increase yield through improved resource use efficiency. The aims of the present study were: (a) to evaluate the effects of different legumes (species and varieties) and barley on grain yield, dry matter production and N uptake of the intercrop treatments compared with the associated cereal sole crop; (b) to assess the effects on the yields of the next grain crop and (c) to determine the accumulation of N in shoots of the crops in a low-input rotation. An experiment was established near Edinburgh, UK, consisting of 12 hydrologically isolated plots. Treatments were a spring barley (Hordeum vulgare cvar Westminster) sole crop and intercrops of barley/white clover (Trifolium repens cvar Alice) and barley/pea (Pisum sativum cvar Zero4 or cvar Nitouche) in 2006. All the plots were sown with spring oats (Avena sativa cvar Firth) in 2007 and perennial ryegrass in 2008. No fertilizers, herbicides or pesticides were used at any stage of the experiment. Above-ground biomass (barley, clover, pea, oat and ryegrass) and grain yields (barley, pea and oat) were measured at key stages during the growing seasons of 2006, 2007 and 2008; land equivalent ratio (LER) was measured only in 2006. At harvest, the total above-ground biomass of barley intercropped with clover (4·56 t biomass/ha) and barley intercropped with pea cvar Zero4 (4·49 t biomass/ha) were significantly different from the barley sole crop (3·05 t biomass/ha; P<0·05). The grain yield of the barley (2006) intercropped with clover (3·36 t grain/ha) was significantly greater than that in the other treatments (P<0·01). The accumulation of N in barley was low in 2006, but significantly higher (P<0·05) in the oat grown the following year on the same plots. The present study demonstrates for the first time that intercrops can affect the grain yield and N uptake of the following crop (spring oats) in a rotation. Differences were also linked to the contrasting legume species and cultivars present in the previous year's intercrop. Legume choice is essential to optimize the plant productivity in intercropping designs. Cultivars chosen for intercropping purposes must take into account the effects upon the growth of the partner crop/s as well as to the following crop, including environmental factors.
This theoretical study examines confined viscous planar jet/wake flows with continuous velocity profiles. These flows are characterized by the shear, confinement, Reynolds number and shear-layer thickness. The primary aim of this paper is to determine the effect of confinement on viscous jets and wakes and to compare these results with corresponding inviscid results. The secondary aim is to consider the effect of viscosity and shear-layer thickness. A spatio-temporal analysis is performed in order to determine absolute/convective instability criteria. This analysis is carried out numerically by solving the Orr–Sommerfeld equation using a Chebyshev collocation method. Results are produced over a large range of parameter space, including both co-flow and counter-flow domains and confinements corresponding to 0.1 < h2/h1 < 10, where the subscripts 1 and 2 refer to the inner and outer streams, respectively. The Reynolds number, which is defined using the channel width, takes values between 10 and 1000. Different velocity profiles are used so that the shear layers occupy between 1/2 and 1/24 of the channel width. Results indicate that confinement has a destabilizing effect on both inviscid and viscous flows. Viscosity is found always to be stabilizing, although its effect can safely be neglected above Re = 1000. Thick shear layers are found to have a stabilizing effect on the flow, but infinitely thin shear layers are not the most unstable; having shear layers of a small, but finite, thickness gives rise to the strongest instability.
This paper considers the dynamics of a thin film of viscous liquid of density ρ coating the underside of a horizontal rigid boundary under the action of surface tension σ and gravity g, and in the lubrication limit. Gravitational instability for inverse wavenumbers larger than the capillary length ℓ = (σ/ρg)1/2) leads to the formation of quasi-static pendent drops of radius ≈3.83ℓ. If the boundary conditions are such as to pin the positions of the drops then the drops slowly drain fluid from the regions between them through thin annular trenches around each drop. A similarity solution is derived and verified numerically in which the film thickness in the intervening regions scales like t−1/4 and that in the trenches like t−1/2. A single drop placed far from boundaries on an otherwise uniform film, and given an initial perturbation, undergoes self-induced quasi-steady translation during which it grows slowly in amplitude by leaving a wake where the film thickness is reduced by an average of 90. It is driven by release of gravitational potential energy as fluid is collected from the film into the lower lying drop. Analysis of Landau–Levich regions around the perimeter of the translating drop predicts its speed and the profile of the wake. Two translating drops may coalesce if they collide, in contrast with the non-coalescence of colliding collars in the analogous one-dimensional problem (Lister et al., J. Fluid Mech. vol. 552, 2006b, p. 311). Colliding drops may also bounce off each other, the outcome depending on the angle of incidence through complex interactions between their surrounding capillary wave fields.
In this theoretical study, a linear spatio-temporal analysis is performed on unconfined and confined inviscid jet/wake flows with surface tension in order to determine convective/absolute instability criteria. There is a single mode that is due to surface tension and many modes that are due to the jet/wake column. In the unconfined case, the full impulse response is considered in the entire outer flow. On the one hand, the surface tension mode propagates slowly in the cross-stream direction but dominates at the front and back of the wavepacket. On the other hand, the jet/wake column modes propagate more quickly in the cross-stream direction and therefore define the boundaries of the central region of the wavepacket. The flow is particularly unstable when these modes interact. For unconfined flows, it is found that at low and intermediate surface tensions the flow can be more absolutely unstable than that without surface tension but at high surface tensions the flow is stabilized. The effect of confinement has previously been studied but not with the inclusion of surface tension. Confinement and surface tension combined cause the transition from convective to absolute instability to occur even with significant coflow. This effect is examined over an infinite domain of density ratios and confinement.
Previously we have examined the effects of diets deficient in folic acid ( − F) or folate deficient with low methionine and choline ( − F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the − F diet. When dams were fed the − F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the − F LM LC group but not in the − F group. Metabolic enzymes associated with lipid metabolism changed in both the − F and − F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the − F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the − F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARα and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.
Nasal swabs were taken from 492 babies born consecutively to residents of two South Wales towns soon after their discharge from maternity hospitals. Staphylococcus aureus was isolated from 352 babies (72%) and in 79 (22%) of these it was resistant to at least one antibiotic. By the time these babies were a year old the prevalence of both sensitive and resistant strains had fallen, so that only 12% still carried nasal staphylococci, but 64% of these organisms were then resistant to penicillin. Administration of penicillin to the baby seemed to be a more important factor in selecting resistant organisms than other antibiotics given to the baby, any antibiotic treatment to other members of the household, or discharge from hospital.