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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.
Despite aspirations to be a world-class national curriculum, the Australian Curriculum (AC) has been criticised as ‘manifestly deficient’ (Australian Government Department of Education and Training, 2014 p. 5) as an inclusive curriculum, failing to meet the needs of all students with disabilities (SWD) and their teachers. There is a need for research into the daily attempts of educators to navigate the tension between a ‘top-down’ system-wide curriculum and a ‘bottom-up’ regard for individual student needs, with a view to informing both policy and practice. This article is the first of two research papers in which we report the findings from a national online Research in Special Education (RISE) Australian Curriculum Survey of special educators in special schools, classes, and units regarding their experience using the AC to plan for and teach SWD. Survey results indicated (a) inconsistent use of the AC as the primary basis for developing learning objectives and designing learning experiences, (b) infrequent use of the achievement standards to support assessment and reporting, and (c) considerable supplementation of the AC from other resources when educating SWD. Overall, participants expressed a lack of confidence in translating the AC framework into a meaningful curriculum for SWD. Implications for policy, practice, and future research are discussed.
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.
In September 2015, an outbreak of Escherichia coli Phage Type 32 with an indistinguishable multi locus variable number tandem repeat analysis profile was identified in Scotland. Twelve cases were identified; nine primary cases, two secondary and one asymptomatic case. Extensive food history investigations identified venison products containing wild venison produced by a single food business operator as the most likely source of the outbreak. Of the nine primary cases, eight had consumed venison products, and one case had not eaten venison themselves but had handled and cooked raw venison in the household. This was the first reported outbreak of Shiga toxin-producing Escherichia coli (STEC) linked to venison products in the UK, and was also notable due to the implicated products being commercially produced and widely distributed. In contrast, previous venison outbreaks reported from other countries have tended to be smaller and related to individually prepared carcases. The outbreak has highlighted some important knowledge gaps in relation to STEC in venison that are currently been investigated via a number of research studies.
Gary P. Baker, Research Associate at the University of East Anglia, and a Researcher at the University of Groningen in the Netherlands.,
Craig L. Lambert, Lecturer in Maritime History at the University of Southampton.,
David Simpkin, Teacher of History at Birkenhead Sixth-Form College.,
J. J. N. Palmer
Given the contribution Andrew Ayton has made to the study of late medieval military history we hope he is not surprised by the production of a Festschrift in his honour. All the editors of this volume were supervised by Andrew for their doctoral studies, and all no doubt thrashed out the general outlines to their theses in one of the infamous ‘Ayton’ meetings that regularly ran into the late evening. Andrew's enthusiasm for his subject was infectious and it is to his credit that many of his former students have gone on to publish contributions on late medieval military and naval history. The papers featured in the present volume highlight the important international impact Andrew's work has had on his students and academic colleagues.
Andrew, a native of Dorset, is in his own words ‘a country dweller at heart’ but has spent much of his working life in the big city. He studied as an undergraduate at the University of Hull in the early 1980s, during which time he undertook several modules taught by Professor John Palmer. John's module on the Hundred Years’ War in particular seems to have kindled Andrew's interest in medieval military history and military communities; it certainly began a fruitful association between two like-minded scholars which was to span some three decades until John's retirement in 2002. Andrew often visited John's home to discuss their latest research and he will be pleased to know he is remembered with some affection by John's children.
After graduating, Andrew spent a brief spell in a ‘real’ job, before returning to Hull to study for his Ph.D. under John Palmer – ‘The Warhorse and Military Service under Edward III’ – and from 1985 to 1987 Andrew was employed, alongside Virginia Davis, on John's Domesday Project. This was a role for which Andrew was particularly well equipped. He had taken John Palmer's special subject on the Domesday Book as an undergraduate, which had provided him with the essential background plus the basic computing skills – in particular related to databases – needed for the research: rare qualifications in the mid-1980s. This period, of course, included the 900th anniversary of Domesday Book, which for Andrew and Virginia entailed a frenetic year, giving lectures and demonstrations around the UK while trying to keep to a research schedule and do some work on their own account.
Here gelatin biotemplated platinum aerogels were prepared from gelatin hydrogels equilibrated in K2PtCl4 solutions ranging from 1-250 mM and reduced with sodium borohydride before supercritical drying in liquid CO2. Scanning electron microscopy revealed an average ligament diameter of 40.6 ± 9.7 nm and a pore size range of ∼10 – 200 nm. Thermogravimetric analysis correlated the ratio of metal content to biotemplate mass as a function of equilibrated platinum ion solution, and X-ray diffractometry indicated platinum metal with no detectable oxide phases. Electrochemical impedance spectroscopy indicated a specific capacitance of 1.92 F/g, with a corresponding specific electrochemical accessible surface area of 6.39 m2/g. Cyclic voltammetry performed in H2SO4 demonstrated biotemplated platinum aerogel potential for catalytic and energy storage applications.
Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.
Gold, palladium, and platinum aerogels were prepared by a rapid, direct solution-based reduction synthesis with densities of 0.54, 0.065, and 0.055 g/cm3, respectively. Salt solutions were reduced at 1:1 (v/v) with dimethylamine borane and sodium borohydride to rapidly form gels within seconds to minutes above a threshold salt concentration and were then rinsed and freeze dried. Au, Pd, and Pt aerogels had no presence of oxide phases confirmed by X-ray diffractometry. Specific surface areas determined with gas physisorption were 3.06, 15.43, and 20.56 m2/g for Au, Pd, and Pt. Electrochemically determined specific capacitances using electrochemical impedance spectroscopy and cyclic voltammetry were 2.18, 4.13, and 4.20 F/g, and 2.67, 7.99, and 5.12 F/g for Au, Pd, and Pt, respectively. The rapid synthesis, high solvent accessible specific surface area, conductivity, and capacitance make these noble metal aerogels candidates for many of catalytic, energy, and sensor applications.
Previous research suggests prevalent vitamin D deficiency in pregnant women residing in South Australia and the Eastern Seaboard, however recent data from Perth, Western Australia (WA) is lacking. This cross-sectional study of n=209 pregnant women (36–40 weeks of gestation, 84% white Caucasian) reports on the vitamin D (25[OH]D) status of a contemporary population of pregnant women in Perth, WA, with a focus on the relative contributions of supplemental vitamin D and ambient ultraviolet (UV) radiation to 25(OH)D levels. Mean (SD) season-adjusted 25(OH)D levels were 77.7 (24.6) nmol/l. The prevalence of vitamin D deficiency (25[OH]D<50 nmol/l) was 13.9%. Ambient UV radiation levels in the 90 days preceding blood draw were significantly correlated with serum 25(OH)D levels (unstandardized coefficient 2.82; 95% CI 1.77, 3.86, P<0.001). Vitamin D supplementation expressed as dose per kg of body weight was also positively correlated with serum 25(OH)D levels (unstandardized coefficient 0.744; 95% CI 0.395, 1.092, P<0.001). In conclusion, this study finds that vitamin D deficiency in a predominantly white Caucasian cohort of pregnant women is less prevalent than has been reported in other studies, providing useful information relating to supplementation and screening in this, and similar, populations.
Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31–60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs.
Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated ‘lifetime ever smokers’ of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses.
Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50–0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (rG-SNP = 1.00, s.e. = 0.09, p < 0.00001).
Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.
While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the “latent vulnerability” engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.
Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9–13 years of age among males (e.g., for neonatal weight: βBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: βGIRLS=−0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March–May; βGIRLS=−0.39; P=0.01) and pre-harvest (September–November; βGIRLS=−0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune-mediated disease.
Information-processing biases may contribute to the intergenerational transmission of depression. There is growing evidence that children of depressed mothers exhibit attentional biases for sad faces. However, findings are mixed as to whether this bias reflects preferential attention toward, versus attentional avoidance of, sad faces, suggesting the presence of unmeasured moderators. To address these mixed findings, we focused on the potential moderating role of genes associated with hypothalamic–pituitary–adrenal axis reactivity. Participants included children (8–14 years old) of mothers with (n = 81) and without (n = 81) a history of depression. Eye movements were recorded while children passively viewed arrays of angry, happy, sad, and neutral faces. DNA was obtained from buccal cells. Children of depressed mothers exhibited more sustained attention to sad faces than did children of nondepressed mothers. However, it is important that this relation was moderated by children's genotype. Specifically, children of depressed mothers who carried reactive genotypes across the corticotropin-releasing hormone type 1 receptor (CHRH1) TAT haplotype and FK506 binding protein 5 (FKBP5) rs1360780 (but not the solute carrier family C6 member 4 [SLC6A4] of the serotonin transporter linked polymorphic region [5-HTTLPR]) exhibited less sustained attention to sad faces and more sustained attention to happy faces. These findings highlight the role played by specific genetic influences and suggest that previous mixed findings may have been due to genetic heterogeneity across the samples.
Background: Clinical perfectionism is a risk and maintaining factor for anxiety disorders, depression and eating disorders. Aims: The aim was to examine the psychometric properties of the 12-item Clinical Perfectionism Questionnaire (CPQ). Method: The research involved two samples. Study 1 comprised a nonclinical sample (n = 206) recruited via the internet. Study 2 comprised individuals in treatment for an eating disorder (n = 129) and a community sample (n = 80). Results: Study 1 factor analysis results indicated a two-factor structure. The CPQ had strong correlations with measures of perfectionism and psychopathology, acceptable internal consistency, and discriminative and incremental validity. The results of Study 2 suggested the same two-factor structure, acceptable internal consistency, and construct validity, with the CPQ discriminating between the eating disorder and control groups. Readability was assessed as a US grade 4 reading level (student age range 9–10 years). Conclusions: The findings provide evidence for the reliability and validity of the CPQ in a clinical eating disorder and two separate community samples. Although further research is required the CPQ has promising evidence as a reliable and valid measure of clinical perfectionism.
Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: −0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Exclusion of children with presumptive Verocytotoxin-producing Escherichia coli (VTEC) from childcare facilities until negative stool specimens are obtained is routine practice that disrupts families. We estimated the shedding and exclusion duration and transmission risk in such facilities. The study population comprised 225 children aged <6 years attending 201 childcare facilities in England with microbiologically confirmed VTEC in 2010–2011. We estimated the interval from onset to first negative specimen, and identified transmission events with secondary cases linked to facilities. The median duration of shedding was 31 days, and median period of exclusion was 39·5 days. Cases attending facilities while shedding VTEC did so for a median of 2 days before exclusion. Secondary cases occurred in 6/83 facilities (7%) attended by infectious cases. Despite evidence of VTEC shedding at facilities, transmission is relatively low. Revised control guidelines could consider supervised return for prolonged asymptomatic shedders.
Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1–17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.