Randomized controlled trial of parent-enhanced CBT compared with individual CBT for obsessive-compulsive disorder in young people

Objective: Obsessive-compulsive disorder (OCD) in young people can be effectively treated with Cognitive Behavior Therapy (CBT). Practice guidelines in the United Kingdom recommend that CBT be delivered with parental or family involvement; however, there is no evidence from randomized trials that this enhances effectiveness. The aim of this trial was to assess if CBT with high parental involvement was more effective than CBT with low parental involvement (individual CBT) in reducing symptoms of OCD. Method: Fifty young people ages 12–17 years with OCD were randomly allocated to individual CBT or parent-enhanced CBT. In parent-enhanced CBT parents attended all treatment sessions; in individual CBT, parents attended only Sessions 1, 7, and the final session. Participants received up to 14 sessions of CBT. Data were analyzed using intent-to-treat and per-protocol methods. The primary outcome measure was the Children’s Yale-Brown Obsessive Compulsion Scale (Scahill et al., 1997). Results: Both forms of CBT significantly reduced symptoms of OCD and anxiety. Change in OCD symptoms was maintained at 6 months. Per-protocol analysis suggested that parent-enhanced CBT may be associated with significantly larger reductions in anxiety symptoms. Conclusions: High and low parental involvement in CBT for OCD in young people were both effective, and there was no evidence that 1 method of delivery was superior on the primary outcome measure. However, this study was small. Future trials should be adequately powered and examine interactions with the age of the young person and comorbid anxiety disorders.

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Communicating probabilistic information from climate model ensembles—lessons from numerical weather prediction

Climate model ensembles are widely heralded for their potential to quantify uncertainties and generate probabilistic climate projections. However, such technical improvements to modeling science will do little to deliver on their ultimate promise of improving climate policymaking and adaptation unless the insights they generate can be effectively communicated to decision makers. While some of these communicative challenges are unique to climate ensembles, others are common to hydrometeorological modeling more generally, and to the tensions arising between the imperatives for saliency, robustness, and richness in risk communication. The paper reviews emerging approaches to visualizing and communicating climate ensembles and compares them to the more established and thoroughly evaluated communication methods used in the numerical weather prediction domains of day-to-day weather forecasting (in particular probabilities of precipitation), hurricane and flood warning, and seasonal forecasting. This comparative analysis informs recommendations on best practice for climate modelers, as well as prompting some further thoughts on key research challenges to improve the future communication of climate change uncertainties.

Problems with binary pattern measures for flood model evaluation

As the calibration and evaluation of flood inundation models are a prerequisite for their successful application, there is a clear need to ensure that the performance measures that quantify how well models match the available observations are fit for purpose. This paper evaluates the binary pattern performance measures that are frequently used to compare flood inundation models with observations of flood extent. This evaluation considers whether these measures are able to calibrate and evaluate model predictions in a credible and consistent way, i.e. identifying the underlying model behaviour for a number of different purposes such as comparing models of floods of different magnitudes or on different catchments. Through theoretical examples, it is shown that the binary pattern measures are not consistent for floods of different sizes, such that for the same vertical error in water level, a model of a flood of large magnitude appears to perform better than a model of a smaller magnitude flood. Further, the commonly used Critical Success Index (usually referred to as F<2 >) is biased in favour of overprediction of the flood extent, and is also biased towards correctly predicting areas of the domain with smaller topographic gradients. Consequently, it is recommended that future studies consider carefully the implications of reporting conclusions using these performance measures. Additionally, future research should consider whether a more robust and consistent analysis could be achieved by using elevation comparison methods instead.

Rare variants in LRRK1 and Parkinson's disease

Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow- up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Improving flood forecasts for better flood preparedness in the UK (and beyond)

This winter (2013/14) coastal storms and an unprecedented amount of rainfall led to significant and widespread flooding across the southern UK. Despite much criticism and blame surrounding the flood events, the Flood Forecasting Centre, a recent development in national-level flood forecasting capabilities for the government and emergency response communities, has received considerable praise. Here we consider how scientific developments and organisational change have led to improvements in the forecasting and flood preparedness seen in this winter's flooding. Although such improvements are admirable, there are many technical and communication challenges that remain for probabilistic flood forecasts to achieve their full potential.