Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion: This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD.

Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation

Background: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. Results: All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Conclusions: Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.

The Met Office Global Coupled model 2.0 (GC2) configuration

The latest coupled configuration of the Met Office Unified Model (Global Coupled configuration 2, GC2) is presented. This paper documents the model components which make up the configuration (although the scientific description of these components is detailed elsewhere) and provides a description of the coupling between the components. The performance of GC2 in terms of its systematic errors is assessed using a variety of diagnostic techniques. The configuration is intended to be used by the Met Office and collaborating institutes across a range of timescales, with the seasonal forecast system (GloSea5) and climate projection system (HadGEM) being the initial users. In this paper GC2 is compared against the model currently used operationally in those two systems. Overall GC2 is shown to be an improvement on the configurations used currently, particularly in terms of modes of variability (e.g. mid-latitude and tropical cyclone intensities, the Madden–Julian Oscillation and El Niño Southern Oscillation). A number of outstanding errors are identified with the most significant being a considerable warm bias over the Southern Ocean and a dry precipitation bias in the Indian and West African summer monsoons. Research to address these is ongoing.

A 2000-year annual record of snow accumulation rates for Law Dome, East Antarctica

Accurate high-resolution records of snow accumulation rates in Antarctica are crucial for estimating ice sheet mass balance and subsequent sea level change. Snowfall rates at Law Dome, East Antarctica, have been linked with regional atmospheric circulation to the mid-latitudes as well as regional Antarctic snowfall. Here, we extend the length of the Law Dome accumulation record from 750 years to 2035 years, using recent annual layer dating that extends to 22 BCE. Accumulation rates were calculated as the ratio of measured to modelled layer thicknesses, multiplied by the long-term mean accumulation rate. The modelled layer thicknesses were based on a power-law vertical strain rate profile fitted to observed annual layer thickness. The periods 380–442, 727–783 and 1970–2009 CE have above-average snow accumulation rates, while 663–704, 933–975 and 1429–1468 CE were below average, and decadal-scale snow accumulation anomalies were found to be relatively common (74 events in the 2035-year record). The calculated snow accumulation rates show good correlation with atmospheric reanalysis estimates, and significant spatial correlation over a wide expanse of East Antarctica, demonstrating that the Law Dome record captures larger-scale variability across a large region of East Antarctica well beyond the immediate vicinity of the Law Dome summit. Spectral analysis reveals periodicities in the snow accumulation record which may be related to El Niño–Southern Oscillation (ENSO) and Interdecadal Pacific Oscillation (IPO) frequencies.

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.

Communicating thematic data quality with web map services

Geospatial information of many kinds, from topographic maps to scientific data, is increasingly being made available through web mapping services. These allow georeferenced map images to be served from data stores and displayed in websites and geographic information systems, where they can be integrated with other geographic information. The Open Geospatial Consortium’s Web Map Service (WMS) standard has been widely adopted in diverse communities for sharing data in this way. However, current services typically provide little or no information about the quality or accuracy of the data they serve. In this paper we will describe the design and implementation of a new “quality-enabled” profile of WMS, which we call “WMS-Q”. This describes how information about data quality can be transmitted to the user through WMS. Such information can exist at many levels, from entire datasets to individual measurements, and includes the many different ways in which data uncertainty can be expressed. We also describe proposed extensions to the Symbology Encoding specification, which include provision for visualizing uncertainty in raster data in a number of different ways, including contours, shading and bivariate colour maps. We shall also describe new open-source implementations of the new specifications, which include both clients and servers.

Testing projected wild bee distributions in agricultural habitats: predictive power depends on species traits and habitat type

Species distribution models (SDM) are increasingly used to understand the factors that regulate variation in biodiversity patterns and to help plan conservation strategies. However, these models are rarely validated with independently collected data and it is unclear whether SDM performance is maintained across distinct habitats and for species with different functional traits. Highly mobile species, such as bees, can be particularly challenging to model. Here, we use independent sets of occurrence data collected systematically in several agricultural habitats to test how the predictive performance of SDMs for wild bee species depends on species traits, habitat type, and sampling technique. We used a species distribution modeling approach parametrized for the Netherlands, with presence records from 1990 to 2010 for 193 Dutch wild bees. For each species, we built a Maxent model based on 13 climate and landscape variables. We tested the predictive performance of the SDMs with independent datasets collected from orchards and arable fields across the Netherlands from 2010 to 2013, using transect surveys or pan traps. Model predictive performance depended on species traits and habitat type. Occurrence of bee species specialized in habitat and diet was better predicted than generalist bees. Predictions of habitat suitability were also more precise for habitats that are temporally more stable (orchards) than for habitats that suffer regular alterations (arable), particularly for small, solitary bees. As a conservation tool, SDMs are best suited to modeling rarer, specialist species than more generalist and will work best in long-term stable habitats. The variability of complex, short-term habitats is difficult to capture in such models and historical land use generally has low thematic resolution. To improve SDMs’ usefulness, models require explanatory variables and collection data that include detailed landscape characteristics, for example, variability of crops and flower availability. Additionally, testing SDMs with field surveys should involve multiple collection techniques.

Sea-breeze dynamics and convection initiation: the influence of convective parameterization in weather and climate model biases

There are some long-established biases in atmospheric models that originate from the representation of tropical convection. Previously, it has been difficult to separate cause and effect because errors are often the result of a number of interacting biases. Recently, researchers have gained the ability to run multiyear global climate model simulations with grid spacings small enough to switch the convective parameterization off, which permits the convection to develop explicitly. There are clear improvements to the initiation of convective storms and the diurnal cycle of rainfall in the convection-permitting simulations, which enables a new process-study approach to model bias identification. In this study, multiyear global atmosphere-only climate simulations with and without convective parameterization are undertaken with the Met Office Unified Model and are analyzed over the Maritime Continent region, where convergence from sea-breeze circulations is key for convection initiation. The analysis shows that, although the simulation with parameterized convection is able to reproduce the key rain-forming sea-breeze circulation, the parameterization is not able to respond realistically to the circulation. A feedback of errors also occurs: the convective parameterization causes rain to fall in the early morning, which cools and wets the boundary layer, reducing the land–sea temperature contrast and weakening the sea breeze. This is, however, an effect of the convective bias, rather than a cause of it. Improvements to how and when convection schemes trigger convection will improve both the timing and location of tropical rainfall and representation of sea-breeze circulations.

Colour relationalism and the real deliverances of introspection

Colour relationalism holds that the colours are constituted by relations to subjects. Anti-relationalists have claimed that this view stands in stark contrast to our phenomenally-informed, pre-theoretic intuitions. Is this claim right? Cohen and Nichols’ recent empirical study suggests not, as about half of their participants seemed to be relationalists about colour. Despite Cohen and Nichols’ study, we think that the anti-relationalist’s claim is correct. We explain why there are good reasons to suspect that Cohen and Nichols’ experimental design skewed their results in favour of relationalism. We then run an improved study and find that most of our participants seem to be anti-relationalists. We find some other interesting things too. Our results suggest that the majority of ordinary people find it no less intuitive that colours are objective than that shapes are objective. We also find some evidence that when those with little philosophical training are asked about the colours of objects, their intuitions about colour and shape cases are similar, but when asked about people’s colour ascriptions, their intuitions about colour and shape cases differ.

The utility of convection-permitting ensembles for the prediction of stationary convective bands

This study examines convection-permitting numerical simulations of four cases of terrain-locked quasi-stationary convective bands over the UK. For each case, a 2.2-km grid-length 12-member ensemble and 1.5-km grid-length deterministic forecast are analyzed, each with two different initialization times. Object-based verification is applied to determine whether the simulations capture the structure, location, timing, intensity and duration of the observed precipitation. These verification diagnostics reveal that the forecast skill varies greatly between the four cases. Although the deterministic and ensemble simulations captured some aspects of the precipitation correctly in each case, they never simultaneously captured all of them satisfactorily. In general, the models predicted banded precipitation accumulations at approximately the correct time and location, but the precipitating structures were more cellular and less persistent than the coherent quasi-stationary bands that were observed. Ensemble simulations from the two different initialization times were not significantly different, which suggests a potential benefit of time-lagging subsequent ensembles to increase ensemble size. The predictive skill of the upstream larger-scale flow conditions and the simulated precipitation on the convection-permitting grids were strongly correlated, which suggests that more accurate forecasts from the parent ensemble should improve the performance of the convection-permitting ensemble nested within it.

Exploring broad mitigation strategies for pollinators in agroecosystems

An increasing world population has put great pressure on agricultural landscapes to continually increase in efficiency whilst avoiding negative impacts on the environment. Protected areas, mass flower crops and agri-environment schemes have been identified as three broad complimentary mitigation strategies to protect and conserve pollinators. Each strategy differs temporarily and spatially but all offer significant benefits to pollinators. It is vital we identify the value of these mitigation strategies and their complementarity if we are to tailor landscape management for optimal results and work towards safeguarding our pollination service.

Sahel decadal rainfall variability and the role of model horizontal resolution

Substantial low-frequency rainfall fluctuations occurred in the Sahel throughout the twentieth century, causing devastating drought. Modeling these low-frequency rainfall fluctuations has remained problematic for climate models for many years. Here we show using a combination of state-of-the-art rainfall observations and high-resolution global climate models that changes in organized heavy rainfall events carry most of the rainfall variability in the Sahel at multiannual to decadal time scales. Ability to produce intense, organized convection allows climate models to correctly simulate the magnitude of late-twentieth century rainfall change, underlining the importance of model resolution. Increasing model resolution allows a better coupling between large-scale circulation changes and regional rainfall processes over the Sahel. These results provide a strong basis for developing more reliable and skilful long-term predictions of rainfall (seasons to years) which could benefit many sectors in the region by allowing early adaptation to impending extremes.

Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.