A pilot evaluation of mindfulness based cognitive therapy for Huntington's disease

Background Many people with the Huntington’s disease (HD) gene, both pre-manifest and manifest, experience low mood, anxiety and other psychological difficulties. Medication can alleviate these difficulties to some extent, but it is not effective for everyone, and is not always the preferred option. Psychological interventions may provide an alternative or additional way of alleviating distress. Aims To see if a particular type of psychological therapy, mindfulness-based cognitive therapy (MBCT), is an acceptable and useful way of alleviating psychological distress for people with the HD gene who are pre-manifest or at an early disease stage. Methods To date 10 pre-manifest HD gene carriers have completed an 8 week course of MBCT led by an experienced mindfulness teacher. The course consisted of weekly 2 hour sessions and up to an hour of home practice every day. Quantitative measures of anxiety, depression, stress and mindfulness were administered pre- and post-course. Qualitative data about participants’ experiences were gathered via semi-structured interview. We are currently recruiting for a second course and aim to run this in Autumn 2016. Results Mean depression levels were low pre-course and thus, unsurprisingly, little change was observed in mean depression post course. However, large effect sizes were seen for mean changes in anxiety and stress and in five aspects of mindfulness (describing, non-judging, non-reacting, observing and acting with awareness). The interview data (and participants’ regular attendance) also suggested that participants found the course acceptable. Furthermore they reported that they thought it beneficial for their wellbeing now and also that the skills they had learnt would be useful in the future. Conclusions MBCT appears to be an acceptable psychological approach for some pre-manifest individuals with the HD gene. Early results indicate that learning mindfulness is possible and can be beneficial. Further research is needed with larger samples to show if it can significantly reduce psychological distress and would benefit from including more individuals with raised depression at baseline to enable changes in depression to be detected. Some recruitment difficulties were encountered and these and the possible implications for future courses will be presented

Stochastic network models for logistics planning in disaster relief

Emergency logistics in disasters is fraught with planning and operational challenges, such as uncertaintyabout the exact nature and magnitude of the disaster, a lack of reliable information about the locationand needs of victims, possible random supplies and donations, precarious transport links, scarcity ofresources, and so on. This paper develops a new two-stage stochastic network flow model to help decidehow to rapidly supply humanitarian aid to victims of a disaster within this context. The model takesinto account practical characteristics that have been neglected by the literature so far, such as budgetallocation, fleet sizing of multiple types of vehicles, procurement, and varying lead times over a dynamicmultiperiod horizon. Attempting to improve demand fulfillment policy, we present some extensions ofthe model via state-of-art risk measures, such as semideviation and conditional value-at-risk. A simpletwo-phase heuristic to solve the problem within a reasonable amount of computing time is also suggested.Numerical tests based on the floods and landslides in Rio de Janeiro state, Brazil, show that the modelcan help plan and organise relief to provide good service levels in most scenarios, and how this dependson the type of disaster and resources. Moreover, we demonstrate that our heuristic performs well for realand random instances

Rubisco small subunits from the unicellular green alga Chlamydomonas complement Rubisco-deficient mutants of Arabidopsis.

Introducing components of algal carbon concentrating mechanisms (CCMs) into higher plant chloroplasts could increase photosynthetic productivity. A key component is the Rubisco-containing pyrenoid that is needed to minimise CO2 retro-diffusion for CCM operating efficiency. Rubisco in Arabidopsis was re-engineered to incorporate sequence elements that are thought to be essential for recruitment of Rubisco to the pyrenoid, namely the algal Rubisco small subunit (SSU, encoded by rbcS) or only the surface-exposed algal SSU α-helices. Leaves of Arabidopsis rbcs mutants expressing 'pyrenoid-competent' chimeric Arabidopsis SSUs containing the SSU α-helices from Chlamydomonas reinhardtii can form hybrid Rubisco complexes with catalytic properties similar to those of native Rubisco, suggesting that the α-helices are catalytically neutral. The growth and photosynthetic performance of complemented Arabidopsis rbcs mutants producing near wild-type levels of the hybrid Rubisco were similar to those of wild-type controls. Arabidopsis rbcs mutants expressing a Chlamydomonas SSU differed from wild-type plants with respect to Rubisco catalysis, photosynthesis and growth. This confirms a role for the SSU in influencing Rubisco catalytic properties

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Phoenix stream : a cold stream in the southern hemisphere

We report the discovery of a stellar stream in the Dark Energy Survey Year 1 (Y1A1) data. The discovery was made through simple color–magnitude filters and visual inspection of the Y1A1 data. We refer to this new object as the Phoenix stream, after its resident constellation. After subtraction of the background stellar population we detect a clear signal of a simple stellar population. By fitting the ridge line of the stream in color–magnitude space, we find that a stellar population with age τ=11.5±0.5 Gyr and [Fe/H]<−1.6, located 17.5±0.9 kpc from the Sun, gives an adequate description of the stream stellar population. The stream is detected over an extension of 8°.1 (2.5 kpc) and has a width of ∼54 pc assuming a Gaussian profile, indicating that a globular cluster (GC) is a probable progenitor. There is no known GC within 5 kpc that is compatible with being the progenitor of the stream, assuming that the stream traces its orbit. We examined overdensities (ODs) along the stream, however, no obvious counterpart-bound stellar system is visible in the coadded images. We also find ODs along the stream that appear to be symmetrically distributed—consistent with the epicyclic OD scenario for the formation of cold streams—as well as a misalignment between the northern and southern part of stream. Despite the close proximity we find no evidence that this stream and the halo cluster NGC 1261 have a common accretion origin linked to the recently found EriPhe OD

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

UKESM1: description and evaluation of the UK Earth System Model

We document the development of the first version of the United Kingdom Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include: a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities, and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall the model performs well, with a stable pre‐industrial state, and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealised simulations show a high climate sensitivity relative to previous generations of models: equilibrium climate sensitivity (ECS) is 5.4 K, transient climate response (TCR) ranges from 2.68 K to 2.85 K, and transient climate response to cumulative emissions (TCRE) is 2.49 K/TtC to 2.66 K/TtC

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms