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Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.
Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.
Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.
Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.
We acknowledge and pay respect to the people of the Yugambeh Nation on whose Land we work, meet and study. We recognise the significant role the past and future Elders play in the life of the University and the region. We are mindful that within and without the buildings, the Land always was and always will be Aboriginal Land.1
This paper introduces staying-with the traces of inter/intra-subjective experience, with and within place, in mapping-making philosophy in environmental education. Through a conceptualisation of philosophy as concepts or knots in an infinite composition of knowledge, rather than separate knowledges, we use staying-with the traces2 as method, whereby our embodied patterns of human and more than human relationality across place and time may engage with philosophy. This grounding of philosophy foregrounds the diverse onto-epistemologies of posthumanism and indigenist3 ways of knowing, acknowledging tensions and searching for the possibilities of connectivity between them. Through an embodied arts-based walking practice, our approach challenges the perpetuation of reductionist perspectives, including nature/culture binaries, within environmental education. We stay with the traces of bird, meeting, tree, watery and concrete in mutual inseparable relation and becoming.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Collaborative care is a community based intervention which typically consists of a number of components. The intervention aims to improve the physical and/or mental health and health care of people with a severe mental illness (SMI).
To explore how collaborative care is implemented.
To assess the effectiveness of collaborative care approaches in comparison to standard care for people with SMI who are living in the community.
A Cochrane Review: The Cochrane Schizophrenia Group Specialised register was searched in April 2011. Fifty one experts in the field of SMI and collaborative care were also contacted.
We included one RCT (306 participants; US veterans with bipolar disorder I or II) in this review. The trial provides data for one comparison: collaborative care versus standard care The reanalysis of data from the one included study indicated that collaborative care significantly reduced psychiatric admissions at year 2 in comparison to standard care (N= 306, 1 RCT, RR 0.75, 95% CI 0.57 to 0.99). Direct intervention (all-treatment) costs of collaborative care at the three year follow up did not differ significantly from standard care,mean difference -$2981.00 (N= 306, 1 RCT95% CI $16934.93 to $10972.93).
One trial at moderate risk of bias suggests that collaborative care may significantly reduce psychiatric admissions. More large, well designed, conducted and reported trials may be required to determine the effects of collaborative care and help inform healthcare professionals and policy makers about the value of collaborative care for people with SMI
Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
At the centre of the Parkes 64—m radio telescope a region of diameter 17 m has recently been resurfaced to improve its efficiency at high frequencies. The first measurements using this section have been made at 22 GHz, in observations of both continuum sources and water tfapour masers. For these observations the receiver front-end used a mixer cooled in liquid nitrogen, followed by a 5 GHz cryogenic parametric amplifier as a second stage. The option of switching against an offset horn was available and the total system
noise temperature was ∽ 750 K.
The 6 GHz transitions of the 2π3/2, J = 5/2 excited state of OH are present in emission in the direction of several OH-emission regions (Rickard et al. 1975; Knowles et al. 1976), and in absorption in compact thermal sources (Gardner and Whiteoak 1975). This has suggested that transitions in the next highest state near 13 GHz (J = 7/2) might also be widely observable. A single detection has already been reported in W3OH by Turner et al. (1970). In this paper we report the observation of narrow-band emission in several other sources.
A study was conducted on a GA(W)-1 wing in order to investigate the effect of testing inverted wings in ground effect at low Reynolds numbers. The wing was tested at a range of ground clearances and Reynolds numbers and results showed that the wing’s performance was dependent on both these parameters. Surface flow-visualisation and numerical simulation results highlighted the existence of a laminar separation bubble on the wing’s suction surface. The results also indicated that both the bubble’s length and the onset of separation were sensitive to ground clearance and Reynolds number. Attempts were made to minimise the wing’s Reynolds number dependency by using transition strips on the suction surface. The transition strip results highlighted the influence that a laminar separation bubble has on the overall performance of the wing and how its presence alters the force enhancement and reduction mechanisms on an inverted wing in ground effect.
To determine the potential predictors of body size dissatisfaction in Chinese children.
The Child’s Body Image Scale was used to assess body size perception and dissatisfaction. BMI was calculated from objectively measured height and weight. Predictors of body size dissatisfaction were examined by logistic regression analysis.
Hong Kong, China.
Six hundred and twenty children (53 % boys, aged 6·1–12·9 years) from a state-run primary school.
Female sex (adjusted OR (AOR)=1·91; 95 % CI 1·32, 2·76), age (AOR=2·62; 95 % CI 1·65, 4·16 for 8–10 years; AOR=2·16; 95 % CI 1·38, 3·38 for >10 years), overweight (AOR=6·23; 95 % CI 3·66, 10·60) and obesity (AOR=19·04; 95 % CI 5·64, 64·32) were positively associated with desire to be thinner. Size misperception was a strong predictor of body size dissatisfaction, irrespective of actual weight status (AOR=1·90; 95 % CI 1·02, 3·54 for overestimation; AOR=0·43; 95 % CI 0·27, 0·67 for underestimation).
Body size dissatisfaction is prevalent among Chinese children as young as 6 years. Female sex, age, overweight, obesity and overestimation of size were associated with increased desire to be thinner. These findings emphasise the importance of preventing body image issues from an early age.
An experimental study incorporating the use of the Background-Oriented Schlieren (BOS) technique was performed to measure the density field of a rectangular supersonic jet. This technique is easier to set up than conventional schlieren since the optical alignment involving the various mirrors, lenses and knife-edge is replaced by a background pattern and a single digital camera. The acquired images which contain information of density gradients in the flow are solved as a Poisson equation and further processed using deconvolution and tomographic algorithms to generate a 3D domain which contains information about the actual density. 2D slices can then be extracted to quantitatively visualise the density along any required planes. The results from supersonic axisymmetric jets are used for validation of the code; these show excellent agreement with pre-validated CFD data. The results for a rectangular supersonic jet are then obtained. These show good agreement with the CFD data, in terms of shock-cell spacing and overall structure of the jet. The technique has proved useful for investigating axis-switching, a phenomenon generally associated with non-axisymmetric jets.
A conservation assessment for the three cycad species native to the Bahamas Islands is presented. Results are based on field surveys on all islands where these species occur. Zamia angustifolia is native to Eleuthera, Zamia integrifolia is native to Abaco, Andros, Eleuthera, Grand Bahama and New Providence, and Zamia lucayana is endemic to Long Island. Z. angustifolia is of the highest conservation concern because of the small number of adult plants, its restricted distribution and the extensive development occurring within its habitat. Z. integrifolia also has a restricted distribution on Eleuthera and Grand Bahama and, although threatened by urban development in New Providence, it is relatively common on Abaco and Andros. Z. lucayana comprises three populations within a narrow strip of land of c. 1 km2; we propose a reassignment of its current conservation status from Endangered to Critically Endangered. We assessed the genetic structure of Z. lucayana based on 15 polymorphic microsatellite DNA loci; this indicated that the three known populations should be considered a single management unit. However, the high number of private alleles suggests that genetic drift, indicative of recent fragmentation, is progressing. We propose in situ conservation strategies, and we also collected germplasm from a total of 24 populations of these three cycad species, for ex situ conservation.
Neurological soft signs (NSS) have been inconsistently reported in obsessive-compulsive disorder (OCD) but may make an impact on treatment response.
The current study examined the presence of NSS in two independent European samples of OCD patients (combined 85 patients and 88 matched healthy controls) using a standardized instrument and conducted a meta-analysis of all published studies identified in the literature with the aim to provide a more definitive answer to the question of whether OCD patients are characterized by increased NSS.
Both empirical studies found elevated NSS scores in patients compared with matched controls. The results of the meta-analysis, which included 15 studies (combined 498 patients and 520 controls) showed large effect sizes (Hedges' g=1.27, 95% confidence interval 0.80–1.75), indicating that OCD patients have significantly higher rates of NSS than matched controls on both sides of the body and in multiple domains (motor coordination, sensory integration and primitive reflexes). The results were robust and remained largely unchanged in our reliability analyses, which controlled for possible outliers. Meta-regression was employed to examine the role of potential variables of interest including sociodemographic variables, symptom severity, medication effects and the use of different instruments, but none of these variables was clearly associated with NSS.
As a group, OCD patients are characterized by increased rates of NSS, compared with healthy controls. However, their origins and potential clinical importance remain to be clarified. Future directions for research are discussed.