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Theoretical models of attention-deficit/hyperactivity disorder implicate neurocognitive dysfunction, yet neurocognitive functioning covers a range of abilities that may not all be linked with inattention. This study (a) investigated the single nucleotide polymorphism (SNP) heritability (h2SNP) of inattention and aspects of neurocognitive efficiency (memory, social cognition, executive function, and complex cognition) based on additive genome-wide effects; (b) examined if there were shared genetic effects among inattention and each aspect of neurocognitive efficiency; and (c) conducted an exploratory genome-wide association study to identify genetic regions associated with inattention. The sample included 3,563 participants of the Philadelphia Neurodevelopmental Cohort, a general population sample aged 8–21 years who completed the Penn Neurocognitive Battery. Data on inattention was obtained with the Kiddie Schedule of Affective Disorders (adapted). Genomic relatedness matrix restricted maximum likelihood was implemented in genome-wide complex trait analysis. Analyses revealed significant h2SNP for inattention (20%, SE = 0.08), social cognition (13%, SE = 0.08), memory (17%, SE = 0.08), executive function (25%, SE = 0.08), and complex cognition (24%, SE = 0.08). There was a positive genetic correlation (0.67, SE = 0.37) and a negative residual covariance (−0.23, SE = 0.06) between inattention and social cognition. No SNPs reached genome-wide significance for inattention. Results suggest specificity in genetic overlap among inattention and different aspects of neurocognitive efficiency.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Developing the ability to regulate one's emotions in accordance with
contextual demands (i.e., emotion regulation) is a central developmental task of
early childhood. These processes are supported by the engagement of the
autonomic nervous system (ANS), a physiological hub of a vast network tasked
with dynamically integrating real-time experiential inputs with internal
motivational and goal states. To date, much of what is known about the ANS and
emotion regulation has been based on measures of respiratory sinus arrhythmia, a
cardiac indicator of parasympathetic activity. In the present study, we draw
from dynamical systems models to introduce two nonlinear indices of cardiac
complexity (fractality and sample entropy) as potential indicators of these
broader ANS dynamics. Using data from a stratified sample of preschoolers living
in high- (i.e., emergency homeless shelter) and low-risk contexts
(N = 115), we show that, in conjunction with
respiratory sinus arrhythmia, these nonlinear indices may help to clarify
important differences in the behavioral manifestations of emotion regulation. In
particular, our results suggest that cardiac complexity may be especially useful
for discerning active, effortful emotion regulation from less effortful
regulation and dysregulation.
This research investigates two factors influencing the ability of tree-ring data to provide accurate 14C calibration information: the fitness and rigor of the statistical model used to combine the data into a curve; and the accuracy, precision and reproducibility of the component 14C data sets. It presents a new Bayesian spline method for calibration curve construction and tests it on extant and new Southern Hemisphere (SH) data sets (also examining their dendrochronology and pretreatment) for the post-Little Ice Age (LIA) interval AD 1500–1950. The new method of construction allows calculation of component data offsets, permitting identification of laboratory and geographic biases. Application of the new method to the 10 suitable SH 14C data sets suggests that individual offset ranges for component data sets appear to be in the region of ± 10 yr. Data sets with individual offsets larger than this need to be carefully assessed before selection for calibration purposes. We identify a potential geographical offset associated with the Southern Ocean (high latitude) Campbell Island data. We test the new methodology for wiggle-matching short tree-ring sequences and use an OxCal simulation to assess the likely precision obtainable by wiggle-matching in the post-LIA interval.
22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.
Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.
This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.
The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.
The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.
Crystals within volcanic rocks record geochemical and textural signatures during magmatic evolution before eruption. Clues to this magmatic history can be examined using crystal size distribution (CSD) studies. The analysis of CSDs is a standard petrological tool, but laborious due to manual hand-drawing of crystal margins. The trainable Weka segmentation (TWS) plugin in ImageJ is a promising alternative. It uses machine learning and image segmentation to classify an image. We recorded back-scattered electron (BSE) images of three volcanic samples with different crystallinity (35, 50 and ≥85 vol. %), using scanning electron microscopes (SEM) of variable image resolutions, which we then tested using TWS. Crystal measurements obtained from the automatically segmented images are compared with those of the manual segmentation. Samples up to 50 vol. % crystallinity are successfully segmented using TWS. Segmentation at significantly higher crystallinities fails, as crystal boundaries cannot be distinguished. Accuracy performance tests for the TWS classifiers yield high F-scores (>0.930), hence, TWS is a successful and fast computing tool for outlining crystals from BSE images of glassy rocks. Finally, reliable CSD’s can be derived using a low-cost desktop SEM, paving the way for a wide range of research to take advantage of this new petrological method.
Gut symbionts can augment resistance to pathogens by stimulating host-immune responses, competing for space and nutrients, or producing antimicrobial metabolites. Gut microbiota of social bees, which pollinate many crops and wildflowers, protect hosts against diverse infections and might counteract pathogen-related bee declines. Bumble bee gut microbiota, and specifically abundance of Lactobacillus ‘Firm-5’ bacteria, can enhance resistance to the trypanosomatid parasite Crithidia bombi. However, the mechanism underlying this effect remains unknown. We hypothesized that the Firm-5 bacterium Lactobacillus bombicola, which produces lactic acid, inhibits C. bombi via pH-mediated effects. Consistent with our hypothesis, L. bombicola spent medium inhibited C. bombi growth via reduction in pH that was both necessary and sufficient for inhibition. Inhibition of all parasite strains occurred within the pH range documented in honey bees, though sensitivity to acidity varied among strains. Spent medium was slightly more potent than HCl, d- and l-lactic acids for a given pH, suggesting that other metabolites also contribute to inhibition. Results implicate symbiont-mediated reduction in gut pH as a key determinant of trypanosomatid infection in bees. Future investigation into in vivo effects of gut microbiota on pH and infection intensity would test the relevance of these findings for bees threatened by trypanosomatids.
Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.
We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.
The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.
The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.
Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)–impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results.
To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin.
Prospective, randomized 2-center study with blinded assessment.
PARTICIPANTS AND SETTING
Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016.
Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non–antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C).
In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001).
In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined.
Thermal resistance across the interface between touching surfaces is critical for many industrial applications. We developed a network model to predict the macroscopic thermal resistance of mechanically contacting surfaces. Contacting interfaces are fractally rough, with small islands of locally intimate contact separated by regions with a wider gas filled boundary gap. Heat flow across the interface is therefore heterogeneous and thus the contact model is based on a network of thermal resistors representing boundary resistance at local contacts and the access resistance for lateral transport to contacts. Molecular dynamics simulations have been performed to characterize boundary resistance of Silicon Alumina interfaces for testing the sensitivity of thermal resistance to contact opening. Boltzmann transport simulations of access resistance in Si are conducted in the ballistic transport regime.
Giardiasis is a treatable disease, caused by the flagellated protozoan parasite, Giardia duodenalis (G. duodenalis). It is one of the most common enteric parasites found globally to cause gastrointestinal disturbances, and infections may result in long-term irritable bowel syndrome-like symptoms. It is a common misconception that giardiasis is associated with foreign travel, which results in locally acquired cases in the UK being underdiagnosed. This report highlights the findings from one large Scottish Health Board, arising from a change in testing methodology, which resulted in the screening of all stools submitted for enteric investigations for G. duodenalis. Previous selection criteria were restricted to patients with a travel history to specific regions of the world, or on the basis of certain clinical details. In this report, clinical details were recorded from samples shown to be positive using two methods: an ELISA-based antigen detection assay and microscopy. Clinical details were assessed for a total of 28 laboratory-confirmed positive cases against the original selection criteria. Twenty-six cases (93%) would have been excluded from Giardia testing if the previous selection criteria had been applied. Although nine cases stated foreign travel, only two had been to regions deemed to be ‘high risk’. Therefore, those seven cases that travelled to perceived ‘low-risk’ regions would have been excluded from testing for this reason. This summary highlights the need for significant improvements to the selection criteria for Giardia testing. Laboratories should be encouraged towards the testing of all routinely submitted stools for this neglected pathogen to ensure cases that are acquired locally are properly identified and treated effectively.
Emerging developmental perspectives suggest that adverse rearing environments promote neurocognitive adaptations that heighten impulsivity and increase vulnerability to risky behavior. Although studies document links between harsh rearing environments and impulsive behavior on substance use, the developmental hypothesis that impulsivity acts as mechanism linking adverse rearing environments to downstream substance use remains to be investigated. The present study investigated the role of impulsivity in linking child abuse and neglect with adult substance use using data from (a) a longitudinal sample of youth (Study 1, N = 9,421) and (b) a cross-sectional sample of adults (Study 2, N = 1,011). In Study 1, the links between child abuse and neglect and young adult smoking and marijuana use were mediated by increases in adolescent impulsivity. In Study 2, indirect links between child abuse and neglect and substance use were evidenced via delayed reward discounting and impulsivity traits. Among impulsivity subcomponents, robust indirect effects connecting childhood experiences to cigarette use emerged for negative urgency. Negative urgency, positive urgency, and sensation seeking mediated the effect of child abuse and neglect on cannabis and alcohol use. Results suggest that child abuse and neglect increases risk for substance use in part, due to effects on impulsivity. Individuals with adverse childhood experiences may benefit from substance use preventive intervention programs that target impulsive behaviors.
Previous research suggests that adult anxiety disorders begin in adolescence and the transition from primary school to secondary school is the first challenge many young adolescents face, which could test their resilience for the first time.
To examine students’ anxiety scores before and after their transition, and what protective and risk factors are present during this challenge.
To determine how the transition can impact anxiety in children, and if protective factors can help decrease the disruption that the transition can cause.
One hundred and eighty-four pupils completed questionnaires in their last term of primary school and during the first term of secondary school. At time 1: the attachment, school membership, and bullying and victimization measures were compared with pupils’ anxiety scores, along with whether their friends or siblings will be attending the same secondary school as them. These analyses will also be conducted once the pupils start secondary school, at time 2.
Secure attachment was associated with lower anxiety and transition anxiety (F(2.56) = 7.255, P = .002; F(2.52) = 19.245, P = .000; F(2.181) = 10.181, P = .000; F(2.53) = 20.545, P = .000). School membership was associated with lower transition anxiety (F(2.181) = 4.151, P = .017; F(2.181) = 3.632, P = .028). Low victimisation was also associated with low anxiety and transition anxiety (F(2.181) = 14.024, P = .000; F(2.181) = 14.529, P = .000; F(2.181) = 9.381, P = .000).
These preliminary results suggest that attachment, school membership and victimisation all impact on pupils anxiety before they transition to secondary school. Therefore, schools could work together to increase school membership and decrease victimisation, particularly for pupils who they suspect will struggle with the transition.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Family dysfunction can test the resilience of adolescents, specifically those from single parent families and those attending schools in more socio-economically challenged areas.
To determine what factors are associated with resilience for those from single parent families or attend schools in more socio-economically challenged areas.
To examine the role of emotional regulation and self-esteem as putative resilience factors in the context of single parents status and socioeconomic disadvantage.
Secondary school pupils from single and dual parent families aged 13 to 15 answered questionnaires at three time points on: emotional regulation, self-esteem, depression and anxiety. A total of 434 pupils took part at time 1, 574 at time 2, and 467 at time 3. The secondary schools were categorised into more and less disadvantaged schools.
Positive self-esteem [F(1.205) = 54.568, P = 0.000; F(1.157) = 35.582, P = 0.000] and emotional regulation [F(1.205) = 46.925, P = 0.000; F(1.157) = 16.583, P = 0.000] were both associated with resilience against depression in adolescents from single parent families. Positive self-esteem [F(1,75) = 102.629, P = 0.000; F(1.355) = 60.555, P = 0.000] and emotional regulation [F(1.60) = 34.813, P = 0.000; F(1.73) = 36.891, P = 0.000] were both associated with resilience against depression in adolescents attending more socio-economically challenged areas.
This research suggests that adolescent resilience against depression may be promoted by improving self-esteem and emotional regulation. Therefore, future interventions could focus on boosting these resilience factors. Further resilience research could include emotional regulation and self-esteem as protective factors for resilience in adolescent mental health. As these variables have been identified, they can help find more pieces to the complex puzzle of resilience.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Giardia duodenalis and Cryptosporidium species are protozoan parasites capable of causing gastrointestinal disease in humans and animals through the ingestion of infective faeces. Whereas Cryptosporidium species can be acquired locally or through foreign travel, there is the mis-conception that giardiasis is considered to be largely travel-associated, which results in differences in laboratory testing algorithms. In order to determine the level of variation in testing criteria and detection methods between diagnostic laboratories for both pathogens across Scotland, an audit was performed. Twenty Scottish diagnostic microbiology laboratories were invited to participate with questions on sample acceptance criteria, testing methods, testing rates and future plans for pathogen detection. Reponses were received from 19 of the 20 laboratories representing each of the 14 territorial Health Boards. Detection methods varied between laboratories with the majority performing microscopy, one using a lateral flow immunochromatographic antigen assay, another using a manually washed plate-based enzyme immunoassay (EIA) and one laboratory trialling a plate-based EIA automated with an EIA plate washer. Whereas all laboratories except one screened every stool for Cryptosporidium species, an important finding was that significant variation in the testing algorithm for detecting Giardia was noted with only four laboratories testing all diagnostic stools. The most common criteria were ‘travel history’ (11 laboratories) and/or ‘when requested’ (14 laboratories). Despite only a small proportion of stools being examined in 15 laboratories for Giardia (2%–18% of the total number of stools submitted), of interest is the finding that a higher positivity rate was observed for Giardia than Cryptosporidium in 10 of these 15 laboratories. These findings highlight that the underreporting of Giardia in Scotland is likely based on current selection and testing algorithms.
Results are presented from our ongoing studies of Titan using ALMA during the period 2012-2015, including a confirmation of the previous detection of vinyl cyanide (C2H3CN), as well as the first spatial map for this species on Titan. Simultaneous mapping of HC3N, CH3CN and C2H5CN reveal characteristic abundance patterns for each species that provide insight into their individual photochemical lifetimes, and help inform our understanding of Titan’s unique, time-variable atmospheric chemistry and global circulation. A time-sequence of HC3N maps covering 38 months reveals a dramatic change in the distribution of this gas consistent with high-altitude photochemical production followed by advection towards the southern (winter) pole, combined with rapid loss in the north after Titan’s 2009 seasonal equinox. The 2015 C2H3CN and C2H5CN maps show abundance peaks in Titan’s southern hemisphere, similar to those observed for the short-lived HC3N molecule. The longer-lived CH3CN, on the other hand, remains more concentrated in the north.
Computerized cognitive–behavioural therapy (cCBT) forms a core component of stepped psychological care for depression. Existing evidence for cCBT has been informed by developer-led trials. This is the first study based on a large independent pragmatic trial to assess the cost-effectiveness of cCBT as an adjunct to usual general practitioner (GP) care compared with usual GP care alone and to establish the differential cost-effectiveness of a free-to-use cCBT programme (MoodGYM) in comparison with a commercial programme (Beating the Blues) in primary care.
Costs were estimated from a healthcare perspective and outcomes measured using quality-adjusted life years (QALYs) over 2 years. The incremental cost-effectiveness of each cCBT programme was compared with usual GP care. Uncertainty was estimated using probabilistic sensitivity analysis and scenario analyses were performed to assess the robustness of results.
Neither cCBT programme was found to be cost-effective compared with usual GP care alone. At a £20 000 per QALY threshold, usual GP care alone had the highest probability of being cost-effective (0.55) followed by MoodGYM (0.42) and Beating the Blues (0.04). Usual GP care alone was also the cost-effective intervention in the majority of scenario analyses. However, the magnitude of the differences in costs and QALYs between all groups appeared minor (and non-significant).
Technically supported cCBT programmes do not appear any more cost-effective than usual GP care alone. No cost-effective advantage of the commercially developed cCBT programme was evident compared with the free-to-use cCBT programme. Current UK practice recommendations for cCBT may need to be reconsidered in the light of the results.
Green galenia is a South African woody prostrate perennial that was first
recorded in Australia in the early 1900s and has since become a serious
threat to indigenous temperate grasslands and surrounding agricultural
areas. Laboratory and field based experiments were conducted to examine the
effect of environmental factors on the germination and viability of green
galenia seed. It was shown that green galenia was able to germinate over a
broad range of temperatures, but short bursts (5 min) of high temperatures
(80 C to 120 C replicating possible exposures to a fire) reduced seed
germination. Seed germination was positively favored by light, declined
rapidly in darkness, and decreased by > 80% at a depth of only 0.5 cm in
soil. Water stress greatly reduced seed germination (45% germination at
osmotic potentials below −0.2 MPa). Germination was completely inhibited at
water potentials of −0.4 to −1.0 MPa. This species is moderately tolerant to
salinity, with over 50% of seeds germinating at low levels of salinity (60
mM NaCl), and moderate germination (49%) occurring at 120 mM NaCl, it can
germinate well in both alkaline (pH 10–83%) and acidic (pH 4–80%)
conditions. The results of this study have contributed to our understanding
of the germination and emergence of green galenia, and this will assist in
developing tools and strategies for the long term management of this noxious
weed in Victoria and other parts of Australia.