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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.
Aims
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.
Method
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.
Results
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.
Conclusions
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.
In recent years, the discovery of massive quasars at $z\sim7$ has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.
Aims
To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).
Method
In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.
Results
Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.
Conclusions
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
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.
Aims
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.
Method
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.
Results
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.
Conclusions
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.
In 2017, dicamba-resistant (DR) soybean was commercially available to farmers in the United States. In August and September of 2017, a survey of 312 farmers from 60 Nebraska soybean-producing counties was conducted during extension field days or online. The objective of this survey was to understand farmers’ adoption and perceptions regarding DR soybean technology in Nebraska. The survey contained 16 questions and was divided in three parts: (1) demographics, (2) dicamba application in DR soybean, and (3) dicamba off-target injury to sensitive soybean cultivars. According to the results, 20% of soybean hectares represented by the survey were planted to DR soybean in 2017, and this number would probably double in 2018. Sixty-five percent of survey respondents own a sprayer and apply their own herbicide programs. More than 90% of respondents who adopted DR soybean technology reported significant improvement in weed control. Nearly 60% of respondents used dicamba alone or glyphosate plus dicamba for POST weed control in DR soybean; the remaining 40% added an additional herbicide with an alternative site of action (SOA) to the POST application. All survey respondents used one of the approved dicamba formulations for application in DR soybean. Survey results indicated that late POST dicamba applications (after late June) were more likely to result in injury to non-DR soybean compared to early POST applications (e.g., May and early June) in 2017. According to respondents, off-target dicamba movement resulted both from applications in DR soybean and dicamba-based herbicides applied in corn. Although 51% of respondents noted dicamba injury on non-DR soybean, 7% of those who noted injury filed an official complaint with the Nebraska Department of Agriculture. Although DR soybean technology allowed farmers to achieve better weed control during 2017 than previous growing seasons, it is apparent that off-target movement and resistance management must be addressed to maintain the viability and effectiveness of the technology in the future.
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.
We examined whether image analysis could separate leafy spurge from other plant species and objects by comparing image analysis to the ocular method of estimating cover. Image analysis was acceptably precise at low and medium cover levels. Image analysis was as repeatable as the ocular method at all sites and cover levels and acceptably reliable at low and medium cover levels but estimated cover lower by 12 to 22% than the ocular method at high cover levels. The average error levels of image analysis and the ocular method did not differ. Estimating leafy spurge cover with a 10% error required only 20 quadrats when image analysis was used, while twice as many quadrats were needed when cover was measured ocularly. Image analysis was recommended as a measurement tool because quantification was efficient, the equipment is inexpensive, and the color prints provide a permanent photo record of the study.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
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.
A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain.
Aims
To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia(n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies.
Method
We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets.
Results
We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia(P<4.1×10−4).
Conclusions
We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.
Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.
Method
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).
Results
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.
Conclusions
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.
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.
The post-disaster response strategy in The Netherlands is unique in that it links scientific institutes, national government and local emergency response organizations. The lynch pin is the Centre for Environmental Health which was founded by the Ministry of Health to improve post-disaster care in The Netherlands. The recently refined Dutch strategy for post-disaster response will be presented and illustrated with a few examples from recent disasters. We will focus on both the role of the Centre and the role of public health Hazmat advisors who are part of the local emergency response organization. The latter advise on the health risks of exposure to CBRN agents. One of the main objectives of the Centre is to prepare guidelines and a structure to ensure transparent and authoritative advice is given to local governments and public health services on the need and value of post-disaster care. The Centre operates a front office, available 24/7, to deliver integrated advice on public health and psychosocial care to local emergency response organizations. A network of experts with a wide range of expertise is on stand-by, whereby the characteristics of the disaster determine which experts compile the advice. The Centre also works closely with several other advisory organizations within the national emergency response organization. Three kinds of advice are delivered. Firstly, as an immediate response (usually within an hour), advice is given on the registration of victims. Secondly, usually within 24 hours, advice is given on the need and value of a health outcome assessment (HOA). Thirdly, if a HOA is decided on, detailed advice is given on its implementation. Another objective of the Centre is strengthening the unique position of regional public health services to deal with post-disaster care. The Centre produces guidelines, tools and training on demand to achieve harmonization and uniformity among these services.
A special cabinet was designed to protect the operator, during post-mortem examinations on animals infected with pathogenic organisms, against the risk of enhaling infected material and the surrounding area from becoming contaminated. The cabinet was suitable for small animals including mice and guinea-pigs.
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.