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Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Poor transition planning contributes to discontinuity of care at the child–adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC).
Methods
A two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial.
Results
The mean difference in HoNOSCA scores between the MT and UC arms at 15 months was −1.11 points (95% confidence interval −2.07 to −0.14, p = 0.03). The cost of delivering the intervention was relatively modest (€17–€65 per service user).
Conclusions
MT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.
Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
In soils and other weathering environments, hematite and goethite are usually formed in the presence of clay minerals. Two-line ferrihydrite was aged in the presence of six different clay minerals in aqueous suspension at 25°C and pH 4, 5, 6 and 7 for 16 years. The transformation into hematite/goethite mixtures was complete in the systems with gibbsite, kaolinite, illite and smectite, but incomplete in those with soil smectite and allophane. Soil smectite and allophane, as well as increasing pH, favoured hematite over goethite. The grainy and multi-domainic hematite crystals in the allophane system contained Si and Al (EDX) and showed a Si – O vibration at ∼920 cm– 1 (FTIR). The unit-cell contraction due to structural Al was counteracted by structural OH, which was removed at 200°C. Heating also increased the magnetic hyperfine field at RT by 1.2 – 1.6 T. Hematite crystals with irregular shape and grainy interior have also been observed in soils.
Some soils from the western Amazon region contain KCl-extractable Al contents 5 to 10 times greater than is typical for highly weathered soils containing predominantly kaolinite and gibbsite. We studied a soil sequence from the Brazilian western Amazon consisting of two Typic Udifluvents on the levee of the Javari River, one Aeric Endoaquent in the backswamp, and two Typic Hapludults on an adjacent terrace. We used wet chemical and X-ray diffraction (XRD) analysis to characterize several size fractions of the 0 to 0.2 m layer of the soils. The exchangeable Al content was very high in the Aquent and Udults (up to 180 mmolc kg–1), but the ‘total’ Fe content was low in all samples (<60 g kg–1). Smectite, vermiculite, hydroxy-interlayered smectite and kaolinite dominate the fine silt and clay fractions of all soils. The Fluvents contain illite in all size fractions and chlorite in the coarse clay and fine silt fractions. The Aquent and Udults have no chlorite, and small amounts of illite occur only in the coarse clay and fine silt fractions. Lepidocrocite was identified in the Aquent. Chlorite, which occurs in the sand, fine silt, and coarse clay fractions of the Fluvents, and pyrophyllite, which occurs in the fine silt fractions of all soils and in the coarse clay of the two Ultisols, appears to be inherited from the parent sediments. The hydroxy-interlayered 2:1 phyllosilicates that form as a result of weathering are the cause of the very high exchangeable Al contents.
The spatial and temporal changes in hydrology and pore water elemental and 87/86Sr compositions were used to determine contemporary weathering rates in a 65 to 226 ky old soil chronosequence formed from granitic sediments deposited on marine terraces along coastal California. Cl-corrected Na, K and Si increased with depth denoting inputs from the weathering of plagioclase and K-feldspar. Solute 87/86Sr exhibited progressive mixing of sea water-dominated precipitation with inputs from less radiogenic plagioclase. Linear approximations to these weathering gradients were used to determine plagioclase weathering rates of between 0.38 and 8.9x10-15 moles m-2 s-1. The lack of corresponding weathering gradients for Ca and Sr indicated short-term equilibrium with the clay ion exchange pool which requires periodic resetting by natural perturbations to maintain continuity, in spite of soil composition changes reflecting the effects of long-term weathering.
Recent advances in ion microprobe instrumentation and techniques have enabled the mapping of C isotope ratios across the whole of a polished plate of a natural diamond from Guaniamo, Venezuela. The resultant map of C isotope variation closely matches the cathodoluminescence image of the growth structure of the diamond and, therefore, indicates an extremely limited scale of diffusion of C atoms sincethetimeof diamond formation. This result is compatible with thelimite d mobility of N atoms shown by theIaAB aggregation stateof thediamond. Inclusions in thediamond aree clogitic, in common with many Guaniamo diamonds with temperatures of formation of around 1200ºC. At such temperature the IaAB aggregation state indicates a mantle residence time on the order of 1 Ga. Such temperatures of formation and mantle residence times are common to many natural diamonds; thus the extremely limited diffusion of C isotopes shown by the mapping indicates that many diamonds will retain the C isotope compositions of their initial formation.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
Methods
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
Results
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
Conclusions
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
We present results from a multiwavelength study of the blazar PKS 1954–388 at radio, UV, X-ray, and gamma-ray energies. A RadioAstron observation at 1.66 GHz in June 2012 resulted in the detection of interferometric fringes on baselines of 6.2 Earth-diameters. This suggests a source frame brightness temperature of greater than 2 × 1012 K, well in excess of both equipartition and inverse Compton limits and implying the existence of Doppler boosting in the core. An 8.4-GHz TANAMI VLBI image, made less than a month after the RadioAstron observations, is consistent with a previously reported superluminal motion for a jet component. Flux density monitoring with the Australia Telescope Compact Array confirms previous evidence for long-term variability that increases with observing frequency. A search for more rapid variability revealed no evidence for significant day-scale flux density variation. The ATCA light-curve reveals a strong radio flare beginning in late 2013, which peaks higher, and earlier, at higher frequencies. Comparison with the Fermi gamma-ray light-curve indicates this followed ~ 9 months after the start of a prolonged gamma-ray high-state—a radio lag comparable to that seen in other blazars. The multiwavelength data are combined to derive a Spectral Energy Distribution, which is fitted by a one-zone synchrotron-self-Compton (SSC) model with the addition of external Compton (EC) emission.
The Herschel Space Observatory was the fourth cornerstone mission in the European Space Agency (ESA) science programme with excellent broad band imaging capabilities in the sub-mm and far-infrared part of the spectrum. Although the spacecraft finished its observations in 2013, it left a large legacy dataset that is far from having been fully scrutinised and still has a large potential for new scientific discoveries. This is specifically true for the photometric observations of the PACS and SPIRE instruments. Some source catalogues have already been produced by individual observing programs, but there are many observations that risk to remain unexplored. To maximise the science return of the SPIRE and PACS data sets, we are in the process of building the Herschel Point Source Catalogue (HPSC) from all primary and parallel mode observations. Our homogeneous source extraction enables a systematic and unbiased comparison of sensitivity across the different Herschel fields that single programs will generally not be able to provide. The catalogue will be made available online through archives like the Herschel Science Archive (HSA), the Infrared Science Archive (IRSA), and the Strasbourg Astronomical Data Center (CDS).
The current study examines the impact of a nutrition rating system on consumers’ food purchases in supermarkets.
Design
Aggregate sales data for 102 categories of food (over 60 000 brands) on a weekly basis for 2005–2007 from a supermarket chain of over 150 stores are analysed. Change in weekly sales of nutritious and less nutritious foods, after the introduction of a nutrition rating system on store shelves, is calculated, controlling for seasonality and time trends in sales.
Setting
One hundred and sixty-eight supermarket stores in the north-east USA, from January 2005 to December 2007.
Subjects
Consumers purchasing goods at the supermarket chain during the study period.
Results
After the introduction of the nutrition ratings, overall weekly food sales declined by an average of 3637 units per category (95 % CI –5961, –1313; P<0·01). Sales of less nutritious foods fell by 8·31 % (95 % CI –13·50, –2·80 %; P=0·004), while sales of nutritious foods did not change significantly (P=0·21); as a result, the percentage of food purchases rated as nutritious rose by 1·39 % (95 % CI 0·58, 2·20 %; P<0·01). The decrease in sales of less nutritious foods was greatest in the categories of canned meat and fish, soda pop, bakery and canned vegetables.
Conclusions
The introduction of the nutrition ratings led shoppers to buy a more nutritious mix of products. Interestingly, it did so by reducing purchases of less nutritious foods rather than by increasing purchases of nutritious foods. In evaluating nutrition information systems, researchers should focus on the entire market basket, not just sales of nutritious foods.