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It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Objective. To identify clinically useful predictors of adherence to medication among persons with schizophrenia. Method. We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory. Results. Less than 25% of consecutive admissions reported being fully compliant. Drug attitudes were the best predictor of regular compliance, symptomatology the best predictor of noncompliance, and memory the best predictor of partial compliance with neuroleptic medication. Conclusions. These data emphasise the complexity of factors that influence whether a person adheres to his medication regimen. Furthermore, they suggest that these factors may vary within the same person over time.
There is limited published data from long-term pediatric bipolar clinical trials with which to guide appropriate treatment decisions. Long-term efficacy and safety of aripiprazole was investigated in this patient population.
296 youths, ages 10-17 year-old with a DSM-IV diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10mg or 30mg) in a 4-week double-blind trial. Completers continued assigned treatments for an additional 26 weeks (double-blind). Efficacy endpoints included mean change from baseline to week 4 and week 30 on the Young Mania Rating Scale; Children's Global Assessment Scale, Clinical Global Impressions-Bipolar version severity scale, General Behavior Inventory, Attention Deficit Hyperactivity Disorders Rating Scale, and time to discontinuation. Tolerability/safety assessments included incidence and severity of AEs, blood chemistries and metabolic parameters.
Over the 30-week course of double-blind treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p< 0.002) and at all scheduled visits from week 2 through week 30 on mean change from baseline in the Y-MRS total score (p<.0001; all visits). Significant improvements were observed on multiple endpoints including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. The 3 most common AEs were somnolence, extrapyramidal disorder, and fatigue. Mean change in body weight z-scores over 30 weeks was not clinically significant.
Over 30-weeks of treatment, both doses of aripiprazole were superior to placebo in the long term treatment of pediatric bipolar patients. Aripiprazole was generally well tolerated.
To describe the infection control preparedness measures undertaken for coronavirus disease (COVID-19) due to SARS-CoV-2 (previously known as 2019 novel coronavirus) in the first 42 days after announcement of a cluster of pneumonia in China, on December 31, 2019 (day 1) in Hong Kong.
A bundled approach of active and enhanced laboratory surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and contact tracing for healthcare workers (HCWs) with unprotected exposure in the hospitals was implemented. Epidemiological characteristics of confirmed cases, environmental samples, and air samples were collected and analyzed.
From day 1 to day 42, 42 of 1,275 patients (3.3%) fulfilling active (n = 29) and enhanced laboratory surveillance (n = 13) were confirmed to have the SARS-CoV-2 infection. The number of locally acquired case significantly increased from 1 of 13 confirmed cases (7.7%, day 22 to day 32) to 27 of 29 confirmed cases (93.1%, day 33 to day 42; P < .001). Among them, 28 patients (66.6%) came from 8 family clusters. Of 413 HCWs caring for these confirmed cases, 11 (2.7%) had unprotected exposure requiring quarantine for 14 days. None of these was infected, and nosocomial transmission of SARS-CoV-2 was not observed. Environmental surveillance was performed in the room of a patient with viral load of 3.3 × 106 copies/mL (pooled nasopharyngeal and throat swabs) and 5.9 × 106 copies/mL (saliva), respectively. SARS-CoV-2 was identified in 1 of 13 environmental samples (7.7%) but not in 8 air samples collected at a distance of 10 cm from the patient’s chin with or without wearing a surgical mask.
Appropriate hospital infection control measures was able to prevent nosocomial transmission of SARS-CoV-2.
The current study evaluated growth performance and digestion responses of finishing bulls fed diets containing 825 g/kg flint maize [dry matter (DM) basis] ground to medium (1.66 mm; MG) or coarse particle sizes (2.12 mm; CG), with added monensin (26 mg/kg; DM basis; MON) or a blend of essential oils (BEO) + exogenous α-amylase (AM; 90 mg/kg + 560 mg/kg commercial product, respectively, DM basis). In Expt 1, 256 Nellore bulls were blocked by initial body weight (BW) (360 ± 11.7 kg) and assigned to 48 pens in a 2 × 2 factorial arrangement of treatments. Effect of a maize particle size × feed additive interaction was not detected for final BW, DM intake (DMI), average daily gain (ADG) and feed efficiency. The DMI was greater for bulls fed BEO + AM v. MON. Final BW and ADG tended to be greater for bulls fed CG than MG maize. An interaction was detected for hot carcass weight which was 11 kg heavier for bulls fed BEO + AM v. MON in diets containing CG, but not MG particle size. In Expt 2, four ruminally cannulated Nellore steers were offered the same treatments as Expt 1, in a 4 × 4 Latin Square design. Intake of most nutrients was greater for steers fed CG than steers fed MG maize. In summary, feeding bulls CG maize increased growth performance and carcass characteristics compared with MG. The combination of BEO + AM resulted in heavier carcass weights compared with MON supplementation when included in diets containing CG maize.
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.
Highly luminescent thin films of zinc tungstate (ZT) have been deposited on top of conventional scintillators (Yttrium Aluminum Perovskite, Yttrium Aluminum Garnet) for electron detection in order to replace the need for a top conducting layer, such as indium tin oxide (ITO) or aluminum, which is non-scintillating and electron absorbing. Such conventional conducting layers serve the single purpose of eliminating electrical charge build-up on the scintillator. The ZT film also eliminates charging, which has been verified by measuring the Duane–Hunt limit and electron emission versus accelerating voltage. The luminescent nature of the ZT film ensures effective detection of low energy electrons from the very top surface of the structure ZT/scintillator, which we call “first-surface scintillator”. The cathodoluminescence has been measured directly with a photodetector and spectrally resolved at different accelerating voltages. All results demonstrate the extended range of operation of the first-surface scintillator, while the conventional scintillators with a top ITO layer decline below 5 kV and have practically no output below 2 kV. Scintillators of different types were integrated in a detection system for backscattered electrons (BSE). The quality of the image at high accelerating voltages is comparable with the conventional scintillator and commercial BSE detector, while the image quality at 1 kV from the first-surface scintillator is superior.
The triazines are one of the most widely used herbicide classes ever developed and are critical for managing weed populations that have developed herbicide resistance. These herbicides are traditionally valued for their residual weed control in more than 50 crops. Scientific literature suggests that atrazine, and perhaps other s-triazines, may no longer remain persistent in soils due to enhanced microbial degradation. Experiments examined the rate of degradation of atrazine and two other triazine herbicides, simazine and metribuzin, in both atrazine-adapted and non-history Corn Belt soils, with similar soils being used from each state as a comparison of potential triazine degradation. In three soils with no history of atrazine use, the t1/2 of atrazine was at least four times greater than in three soils with a history of atrazine use. Simazine degradation in the same three sets of soils was 2.4 to 15 times more rapid in history soils than non-history soils. Metribuzin in history soils degraded at 0.6, 0.9, and 1.9 times the rate seen in the same three non-history soils. These results indicate enhanced degradation of the symmetrical triazine simazine, but not of the asymmetrical triazine metribuzin.
Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.
The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.
We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.
These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.
Objectives: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Methods: Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. Results: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Conclusions: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529–538)
The fragmented ecosystems along the Niagara Escarpment World Biosphere Reserve provide important habitats for biota including lichens. Nonetheless, the Reserve is disturbed by dense human populations and associated air pollution. Here we investigated patterns of lichen diversity within urban and rural sites at three different locations (Niagara, Hamilton, and Owen Sound) along the Niagara Escarpment in Ontario, Canada. Our results indicate that both lichen species richness and community composition are negatively correlated with increasing human population density and air pollution. However, our quantitative analysis of community composition using canonical correspondence analysis (CCA) indicates that human population density and air pollution is more independent than might be assumed. The CCA analysis suggests that the strongest environmental gradient (CCA1) associated with lichen community composition includes regional pollution load and climatic variables; the second gradient (CCA2) is associated with local pollution load and human population density factors. These results increase the knowledge of lichen biodiversity for the Niagara Escarpment and urban and rural fragmented ecosystems as well as along gradients of human population density and air pollution; they suggest a differential influence of regional and local pollution loads and population density factors. This study provides baseline knowledge for further research and conservation initiatives along the Niagara Escarpment World Biosphere Reserve.
Interfacing organic electrochemical transistors (OECTs) with biological systems holds considerable promise for building-sensitive biosensors and diagnostic tools. We present a simple model that describes the performance of biosensors in which an OECT is integrated with a biological barrier layer. Using experimentally derived parameters we explore the limits of sensitivity and find that it is dependent on the resistance of the barrier layer. This work provides guidelines on how to optimize biosensors in which OECTs transduce changes in the impedance of biological layers, including lipid bilayer membranes and confluent cell layers.
Mineralized soil nitrogen (N) is an important source of N for grassland production. Some soils can supply large quantities of plant-available N through mineralization of soil organic matter. Grass grown on such soils require less fertilizer N applications per unit yield. A reliable, accurate and user-friendly method to account for soil N supply potential across a large diversity of soils and growing conditions is needed to improve N management and N recommendations over time. In the current study, the effectiveness of chemical N tests and soil properties to predict soil N supply for grass uptake across 30 Irish soil types varying in N supply potential was investigated under controlled environmental conditions. The Illinois soil N test (ISNT) combined with soil C : N ratio provided a good estimate of soil N supply in soils with low residual mineral N. Total oxidized N (TON) had the largest impact on grass dry matter (DM) yield and N uptake across the 30 soil types, declining in its influence in later growth periods. This reflected the high initial mineral N levels in these soils, which declined over time. In the current study, a model with ISNT-N, C : N and TON (log TON) best explained variability in grass DM yield and N uptake. All three rapid chemical soil tests could be performed routinely on field samples to provide an estimate of soil N supply prior to making N fertilizer application decisions. It can be concluded that these soil tests, through their assessment of soil N supply potential, can be effective tools for N management on grassland; however, field studies are needed to evaluate this under more diverse growing conditions.
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
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.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
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
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.
The nitrogen (N) cycle is one of the best studied elemental cycles. However, the N flows and transformations, in particular in aggregated soils, at small scales and in plant–soil systems are not yet fully understood. Analytical and molecular techniques are now available to address N dynamics at small scales. The methodological advances should go hand in hand with the development of suitable mathematical models addressing the small scale and the full complexity of the many interacting effects. The importance of denitrification within the N cycle is highlighted and used as an example of the progress achieved in recent times. Research gaps and possible research pathways are outlined.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis.
Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n = 23) and not exposed to cannabis (n = 32) in the intervening period was compared using tensor-based morphometry (TBM).
Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected = 0.029, t = 3.88) and left superior frontal lobe GM (pcorrected = 0.026, t = 4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval.
Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.