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Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples.
We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting ‘psychosis risk’ enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines.
Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70.
Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS.
Abnormal body mass index (BMI) has been associated with development of psychopathology. This association in children is well documented, for both overweight and underweight children. However, the association between change in BMI and the development of psychopathology has been less investigated.
To investigate the association between change in BMI between childhood and adolescence and psychopathology in adolescence.
Data from the Growing Up in Ireland cohort were used. We investigated the ’98 cohort (also known as the child cohort) at age 9/13. BMI, defined using internationally recognised definitions as underweight, healthy or overweight, was used as the exposure, and abnormal Strength and Difficulties Questionnaire scores were used as the outcome. Logistic regression was undertaken for the analysis. All analyses were adjusted for confounders.
A change to overweight from healthy BMI was significantly associated with increased risk of psychopathology (adjusted OR 1.66; 95% CI 1.19–2.32). Both change from underweight to healthy (adjusted OR 0.12; 95% CI 0.03–0.43) or from overweight to healthy (adjusted OR 0.47; 95% CI 0.79–0.8) was associated with a significantly reduced risk of developing psychopathology.
As a child’s BMI returns to within the healthy range, their risk of adolescent psychopathology is reduced. Interventions to restore healthy BMI, in both underweight and overweight, children may reduce their risk of adolescent psychopathology.
In 1928, Noel Morss was shown “irrigation ditches” along Pleasant Creek on the Dixie National Forest near Capitol Reef National Park, Utah, by a local guide who contended they were ancient. We relocated the site and mapped the route of an unusual mountain irrigation canal. We conducted excavations and employed OSL and AMS 14C showing historic irrigation, and an earlier event between AD 1460 and 1636. Geomorphic evidence indicates that the canal existed prior to this time, but we cannot date its original construction. The canal is 7.2 km long, originating at 2,450 m asl and terminating at 2,170 m asl. Less than half of the system was hand constructed. We cannot ascribe the prehistoric use-event to an archaeological culture, language, or ethnic group, but the 100+ sites nearby are largely Fremont in cultural affiliation. We also report the results of experimental modeling of the capital and maintenance costs of the system, which holds implications for irrigation north of the Colorado River and farming during the Little Ice Age. The age of the prehistoric canal is consistent with a fragmentary abandonment of farming and continuity between ancient and modern tribes in Utah.
Acute rheumatic fever (ARF), an auto-immune response to a group A Streptococcus infection and precursor to rheumatic heart disease (RHD), remains endemic in many socio-economically disadvantaged settings. A Global Resolution on ARF and RHD was recently adopted at the 71st World Health Assembly where governments committed to improving efforts to prevent and control ARF and RHD. To inform these efforts, the objectives of this study were to examine associations between childhood ARF in the UK between 1958 and 1969 and a range of environmental and social factors. Of 17 416 children from the nationally representative birth cohort of the National Child Development Study, ARF was reported in 23 children during early childhood (between birth and the 7-year follow-up) and in 29 additional children during middle childhood (between the 7- and 11-year follow-ups). Risk factors associated with ARF in both early and middle childhood were: a large family size; attendance at a private nursery or class; a history of nephritis, kidney or urinary tract infections; and a history of throat or ear infections. Risk factors for ARF in early childhood alone were families with fathers in a professional or semi-professional occupation and families who moved out of their local neighbourhood. Risk factors in late childhood alone included overcrowding and free school meals. These data suggest that prevention strategies in ARF endemic settings may be enhanced by targeting, for example, new members entering a community and children in environments of close contact, such as a nursery or shared bedrooms.
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’.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
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.
The U.K. 1.2 metre Schmidt Telescope acquired its first full aperture objective prism in 1975. This was a very low dispersion prism (2400 Å/mm at 4300 Å) which has been found to be particularly useful in searching for faint QSO’s.
Our knowledge of the universe comes from recording the photon and particle fluxes incident on the Earth from space. We thus require sensitive measurement across the entire energy spectrum, using large telescopes with efficient instrumentation located on superb sites. Technological advances and engineering constraints are nearing the point where we are recording as many photons arriving at a site as is possible. Major advances in the future will come from improving the quality of the site. The ultimate site is, of course, beyond the Earth’s atmosphere, such as on the Moon, but economic limitations prevent our exploiting this avenue to the degree that the scientific community desires. Here we describe an alternative, which offers many of the advantages of space for a fraction of the cost: the Antarctic Plateau.
The multi-object spectroscopic facility FOCAP at the Anglo-Australian Telescope has been used to obtain spectra centred at the Ca II IR triplet of 14 stars in the field of the Sextans dwarf spheroidal (dSph) galaxy. This satellite of our own Galaxy was recently discovered by Irwin et al. (1990) from APM measures of UK Schmidt Telescope photographic plates.
We present the results of a multi-wavelength investigation of the dwarf galaxy populations in three interacting galaxy groups: NGC 871/6/7, NGC 3166/9, NGC 4725/47. Using degree-scale Giant Metrewave Radio Telescope Hi mosaics and deep optical photometry from the Canada-France-Hawaii Telescope, we measured the Hi and stellar properties of the gas-rich low-mass group members to classify each one as a classical dwarf galaxy, a short-lived tidal knot or a tidal dwarf galaxy (TDG). Our observations detect several dwarf irregulars and various tidal knots. We identify four potentially long-lived tidal objects in the three groups, implying that TDGs are not readily produced. The tidal objects examined in this small survey also appear to have a wider variety of properties than TDGs formed in current simulations.
Impulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis.
We focused on five subfacets of impulsivity: self-reported attentional, motor, and non-planning impulsivity, self-reported sensation seeking, and a behavioral measure of motor inhibition (stop signal reaction time; SSRT). We examined these facets within and across disorder proband and co-twin groups, modeled heritability, and tested for endophenotypic patterning in a sample of twin pairs recruited from the Swedish Twin Registry (N = 420).
We found evidence of moderate to high levels of heritability for all five subfacets. All three proband groups and their unaffected co-twins showed elevations on attentional, motor, and non-planning impulsivity. Schizophrenia probands (but not their co-twins) showed significantly lower sensation seeking, and schizophrenia and bipolar disorder probands (but not in their co-twins) had significantly longer SSRTs, compared with healthy controls and the other groups.
Attentional, motor, and non-planning impulsivity emerged as potential shared endophenotypes for the three disorders, whereas sensation seeking and SSRT were associated with phenotypic affection but not genetic loading for these disorders.
A series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed.
At baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models.
CHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment.
In CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.
White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.
Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.
We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.
WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.
We present the first results from a study of the radio continuum properties of galaxies in the 2dF Galaxy Redshift Survey, (2dFGRS) based on thirty 2dF fields covering a total area of about 100 deg2. About 1·5% of galaxies with bJ < 19·4 mag. are detected as radio continuum sources in the NRAO VLA Sky Survey (NVSS). Of these, roughly 40% are star-forming galaxies and 60% are active galaxies (mostly low-power radio galaxies and a few Seyferts). The combination of 2dFGRS and NVSS will eventually yield a homogeneous set of around 4000 radio-galaxy spectra, which will be a powerful tool for studying the distribution and evolution of both AGN and starburst galaxies out to z ∼ 0·3.
Psychotic symptoms, also termed psychotic-like experiences (PLEs) in the absence of psychotic disorder, are common in adolescents and are associated with increased risk of schizophrenia-spectrum illness in adulthood. At the same time, schizophrenia is associated with deficits in social cognition, with deficits particularly documented in facial emotion recognition (FER). However, little is known about the relationship between PLEs and FER abilities, with only one previous prospective study examining the association between these abilities in childhood and reported PLEs in adolescence. The current study was a cross-sectional investigation of the association between PLEs and FER in a sample of Irish adolescents.
The Adolescent Psychotic-Like Symptom Screener (APSS), a self-report measure of PLEs, and the Penn Emotion Recognition-40 Test (Penn ER-40), a measure of facial emotion recognition, were completed by 793 children aged 10–13 years.
Children who reported PLEs performed significantly more poorly on FER (β=−0.03, p=0.035). Recognition of sad faces was the major driver of effects, with children performing particularly poorly when identifying this expression (β=−0.08, p=0.032).
The current findings show that PLEs are associated with poorer FER. Further work is needed to elucidate causal relationships with implications for the design of future interventions for those at risk of developing psychosis.
Recent (≤ 0.5 Gyr) star formation histories have a large impact on the observable properties of galaxies. Using HST/ACS observations, we have used the blue helium burning (BHeB) stars to construct spatially resolved star formation histories of M81 group dwarf galaxies with a time resolution of roughly 30 Myr over the last 500 Myr. We have designed a sample of ten galaxies spanning ranges of 6 magnitudes in luminosity, 1000 in current star formation rate, and 0.5 dex in metallicity. The ACS observations allow us to directly observe the strength and spatial relationships of all of the recent star formation in these galaxies. These observations are complemented by high-quality ancillary data (e.g., Spitzer, UV/optical/H-alpha/NIR, VLA HI). Our resolved star formation maps will be compared with star formation rates inferred from H-alpha, UV, and IR observations – allowing an independent calibration of these techniques. Given the ranges in metallicity, these observations will provide calibrations of stellar evolution tracks for young, low metallicity stars. These observations will also enable us to construct prescriptions of how star formation and feedback depend on metallicity, size, gas content, and current star formation rates in galaxies. Finally, I note that the new observations becoming available as a part of the ANGST (ACS Nearby Galaxies Survey Treasury Program) will allow a large number of dwarf galaxies to be analyzed in this way.