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Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Many materials, both fissionable and non-fissionable, become very radioactive when subjected to nuclear radiations. This radioactivity results in a high background level in X-ray diffraction studies and becomes a limiting factor in an analysis of radiation damage. A description is given of special techniques that are used to minimize this background and produce optimum diffraction conditions. The radioactive intensity of irradiated X-ray specimens varies from levels that are only mildly troublesome to levels that are extremely hazardous to personnel. The diffraction methods employed at the various levels are explained. An example of the radioactive energy spectrum of a specimen is given to show the method of selecting the best operating conditions and techniques.
Curiosity – the intrinsic desire to acquire new information – is a key factor for learning and memory in everyday life. To date, there has been very little research on curiosity and, therefore, our understanding of how curiosity impacts learning is relatively poor. In this chapter, we give an overview of psychological theories of curiosity and how initial research has focused on curiosity as a specific personality characteristic (i.e. trait curiosity). We then review recent findings on curiosity emerging in experimental psychology and cognitive neuroscience. Rather than examining trait curiosity, this recent line of research explores how temporary states of curiosity affect cognitive processes. Recent findings suggest that curiosity states elicit activity in the brain's dopaminergic circuit and thereby enhance hippocampus-dependent learning for information associated with high curiosity but also for incidental information encountered during high-curiosity states. We speculate how this new line of curiosity research could help to better understand the mechanisms underlying curiosity-related learning and potentially lead to a fruitful avenue of translating laboratory-based findings on curiosity into educational settings.
Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.
Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15–30) in cohort 1 and 6/1000 (95% CI 3–8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18–3.48) and 1.41 (95% CI 0.80–2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.
Sleep disturbances are prominent correlates of acute mood episodes and inadequate recovery in bipolar disorder (BD), yet the mechanistic relationship between sleep physiology and mood remains poorly understood. Using a series of pre-sleep mood inductions and overnight sleep recording, this study examined the relationship between overnight mood regulation and a marker of sleep intensity (non-rapid eye movement sleep slow wave activity; NREM SWA) during the interepisode phase of BD.
Adults with interepisode BD type 1 (BD; n = 20) and healthy adult controls (CTL; n = 23) slept in the laboratory for a screening night, a neutral mood induction night (baseline), a happy mood induction night, and a sad mood induction night. NREM SWA (0.75–4.75 Hz) was derived from overnight sleep EEG recordings. Overnight mood regulation was evaluated using an affect grid pleasantness rating post-mood induction (pre-sleep) and the next morning.
Overnight mood regulation did not differ between groups following the sad or happy inductions. SWA did not significantly change for either group on the sad induction night compared with baseline. In BD only, SWA on the sad night was related to impaired overnight negative mood regulation. On the happy induction night, SWA increased relative to baseline in both groups, though SWA was not related to overnight mood regulation for either group.
These findings indicate that SWA disruption may play a role in sustaining negative mood state from the previous night in interepisode BD. However, positive mood state could enhance SWA in bipolar patients and healthy adults.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
We propose a novel explanation for the observed increase in the correlation of commodity prices over the past decade. In contrast to theories that rely on the increased influence of financial speculators, we examine the effect of interest rates on the volatility and correlation of commodity prices via a panel GARCH model. In theory, lower interest rates decrease the volatility of prices, as lower inventory costs promote the smoothing of transient shocks, and increase price correlation if common shocks are more persistent than idiosyncratic shocks. Empirically, we find that price volatility attributable to transitory shocks declines with interest rates, whereas particularly for metals prices, price correlation increases as interest rates decline.
A systematic review was conducted to evaluate whether healthier dietary consumption among children and adolescents impacts executive functioning. PubMed, Education Resources Information Center, PsychINFO and Thomson Reuters’ Web of Science databases were searched, and studies of executive functioning among children or adolescents aged 6–18 years, which examined food quality, macronutrients and/or foods, were included. Study quality was also assessed. In all, twenty-one studies met inclusion criteria. Among the twelve studies examining food quality (n 9) or macronutrient intakes (n 4), studies examining longer-term diet (n 6) showed positive associations between healthier overall diet quality and executive functioning, whereas the studies examining the acute impact of diet (n 6) were inconsistent but suggestive of improvements in executive functioning with better food quality. Among the ten studies examining foods, overall, there was a positive association between healthier foods (e.g. whole grains, fish, fruits and/or vegetables) and executive function, whereas less-healthy snack foods, sugar-sweetened beverages and red/processed meats were inversely associated with executive functioning. Taken together, evidence suggests a positive association between healthy dietary consumption and executive functioning. Additional studies examining the effects of healthier food consumption, as well as macronutrients, on executive functioning are warranted. These studies should ideally be conducted in controlled environments and use validated cognitive tests.
In order to ensure the quality of the source catalogue derived from the SASS processing an automatic as well as a visual screening procedure was applied to 1378 survey fields. Most (94%) of the 18,811 sources were confirmed by this screening process. The rest is flagged for various reasons. Broad band images are available for a subset of the flagged sources. Details of the screening process can be found at www.rosat.mpe-garching.mpg.de/survey/rass-bsc/doc.html.
Metabolic adaptation includes an array of concerted metabolic and endocrine events that enable dairy cows bridging the period of energy deficit at the onset of lactation. The present study evaluated metabolic, endocrine and reticuloruminal pH changes in 30 (25 Holstein and five Simmental) periparturient dairy cows experiencing variable lipolysis early postpartum. Cows were fed the same close-up and fresh lactation diets and kept in the same management conditions. Blood samples were collected at day 14, and day 4, relative to expected parturition, and at day 2, and day 21 postpartum, and serum metabolites and hormones related to glucose and lipid metabolism, as well as concentrations of several liver enzymes and acute phase proteins were determined. Additionally, reticuloruminal pH was monitored every 10 min over the last 3 days of the observation period. BW and milk yields were recorded and balances of energy and protein were assessed. Based on serum concentration of non-esterified fatty acids (NEFA) postpartum, cows were retrospectively classified into low (n=8), medium (n=11), and high (n=11) lipolysis groups, with NEFA levels of <0.4 mmol/l, between 0.4 and 0.7 mmol/l, and >0.7 mmol/l, respectively. Overall, elevated NEFA concentrations in the High group went along with a higher ratio of NEFA to cholesterol and reduced insulin sensitivity. While serum glucose, energy deficit and BW loss did not differ, cows of the High group exhibited increased lactate concentrations in the serum, compared with the Medium group. No differences in liver enzymes and acute phase proteins were evidenced among fat mobilization groups, whereas concentration of serum billirubin was lowest in the Low group after parturition. Data of milk yield and milk energy output showed no differences among groups, despite divergences in calculated energy balance and BW change postpartum. Cows of the Low group tended to increase dry matter intake but also showed longer time duration of pH below 6.0 in the reticulorumen (on average 299 min/day compared with 99 and 91 min/day for Medium and High groups, respectively). Differences in metabolic, endocrine and reticuloruminal pH responses indicate diverse metabolic adaptation strategies of early-lactation cows to cope with energy deficit postpartum.
Plant growth and insect resistance characteristics were determined for two Brassica napus Linnaeus (Brassicaceae) lines, AtGL3+ and K-5-8, developed for enhanced trichome densities relative to their parental cultivar Westar. In the field, both transgenic lines had glabrous cotyledons that curled upwards at emergence but flattened with time, and young leaves with elevated trichome density. Flea beetle (Phyllotreta cruciferae (Goeze) and Phyllotreta striolata (Fabricius); Coleoptera: Chrysomelidae) feeding was reduced on true leaves of both lines by 30–50% compared with insecticide-free Westar. Flea beetle feeding levels on cotyledons of the two hairy-leaved lines were lower than on unprotected Westar and similar to those seen on insecticide-treated Westar. Antixenosis and antibiosis resistance was observed when diamondback moths (Plutella xylostella (Linnaeus); Lepidoptera: Plutellidae) interacted with the hairy AtGL3+ and K-5-8 lines in the laboratory. Although the numbers of eggs laid by female diamondback moths on the transformed lines were similar to or higher than on Westar, in feeding bioassays larvae moved off AtGL3+ plants and larval feeding injury decreased on the transformed lines compared with Westar leaves. No agronomic or seed yield penalties were found for plants of K-5-8. These data highlight the utility of manipulating trichome regulatory genes to increase plant resistance against brassicaceous insect pests.
The capabilities of the X-ray Timing Explorer (XTE) are described with particular attention paid to current scientific problems it will address from galactic neutron star systems to active galactic nuclei. It features a low-background continuous 2-200 keV response with large apertures (a 0.63-m2 proportional counter array and a 0.16-m2 dual rocking NaI/CsI scintillation array). Rapid response (in hours) to temporal phenomena, e.g. transients, is obtained by virtue of a scanning all-sky monitor and rapid maneuverability. XTE will carry out detailed energy-resolved studies of phenomena close to neutron stars (e.g. QPO’s) because of its sub-millisecond timing (to 10 μs), its high telemetry rates (to 256 kb/s), and the high throughput of its data system (to ≳ 2 × 105 c s−1).
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD).
Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI).
45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ21 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ21 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ21 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ21 = 11.7, p < 0.001).
Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6–74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.
Though poorly defined, hypersomnia is associated with negative health outcomes and new-onset and recurrence of psychiatric illness. Lack of definition impedes generalizability across studies. The present research clarifies hypersomnia diagnoses in bipolar disorder by exploring possible subgroups and their relationship to prospective sleep data and relapse into mood episodes.
A community sample of 159 adults (aged 18–70 years) with bipolar spectrum diagnoses, euthymic at study entry, was included. Self-report inventories and clinician-administered interviews determined features of hypersomnia. Participants completed sleep diaries and wore wrist actigraphs at home to obtain prospective sleep data. Approximately 7 months later, psychiatric status was reassessed. Factor analysis and latent profile analysis explored empirical groupings within hypersomnia diagnoses.
Factor analyses confirmed two separate subtypes of hypersomnia (‘long sleep’ and ‘excessive sleepiness’) that were uncorrelated. Latent profile analyses suggested a four-class solution, with ‘long sleep’ and ‘excessive sleepiness’ again representing two separate classes. Prospective sleep data suggested that the sleep of ‘long sleepers’ is characterized by a long time in bed, not long sleep duration. Longitudinal assessment suggested that ‘excessive sleepiness’ at baseline predicted mania/hypomania relapse.
This study is the largest of hypersomnia to include objective sleep measurement, and refines our understanding of classification, characterization and associated morbidity. Hypersomnia appears to be comprised of two separate subgroups: long sleep and excessive sleepiness. Long sleep is characterized primarily by long bedrest duration. Excessive sleepiness is not associated with longer sleep or bedrest, but predicts relapse to mania/hypomania. Understanding these entities has important research and treatment implications.
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.
Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders.
The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.
These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.
We examined changes in a community of seedlings/saplings 10–150 cm tall associated with the presence of a widely invasive plant, Lantana camara and environmental covariates along 67 randomly located transects, in Mudumalai, India. We compared plant species assemblage and grass cover in L. camara-invaded and uninvaded plots in three habitats. Multivariate analyses revealed a significant association of all environmental covariates with plant species assemblage. Pairwise tests indicated that L. camara was significantly associated with changes in plant species assemblage and grass cover within the moist and dry deciduous forest, but not in the thorn forest. The relationship between L. camara and that of elephant browse plants varied with species. A linear regression analysis indicated that L. camara invasion was the only significant predictor of grass occupancy. Our results indicate that in addition to other factors, L. camara was associated with altering plant species assemblage, some elephant browse plants and grass cover in the moist and dry deciduous forest. It appears that L. camara can have a major effect on diversity within this reserve, but whether this effect is by L. camara driving the change or being associated with other habitat change requires further experimental evidence.
Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question.
Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes.
Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6–72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors.
Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.