The SPECTRUM Consortium: a new UK Prevention Research Partnership consortium focussed on the commercial determinants of health, the prevention of non-communicable diseases, and the reduction of health inequalities

The main causes of non-communicable diseases (NCDs), health inequalities and health inequity include consumption of unhealthy commodities such as tobacco, alcohol and/or foods high in fat, salt and/or sugar. These exposures are preventable, but the commodities involved are highly profitable. The economic interests of ‘Unhealthy Commodity Producers’ (UCPs) often conflict with health goals but their role in determining health has received insufficient attention. In order to address this gap, a new research consortium has been established. This open letter introduces the SPECTRUM (Shaping Public hEalth poliCies To Reduce ineqUalities and harM) Consortium: a multi-disciplinary group comprising researchers from 10 United Kingdom (UK) universities and overseas, and partner organisations including three national public health agencies in Great Britain (GB), five multi-agency alliances and two companies providing data and analytic support. Through eight integrated work packages, the Consortium seeks to provide an understanding of the nature of the complex systems underlying the consumption of unhealthy commodities, the role of UCPs in shaping these systems and influencing health and policy, the role of systems-level interventions, and the effectiveness of existing and emerging policies. Co-production is central to the Consortium’s approach to advance research and achieve meaningful impact and we will involve the public in the design and delivery of our research. We will also establish and sustain mutually beneficial relationships with policy makers, alongside our partners, to increase the visibility, credibility and impact of our evidence. The Consortium’s ultimate aim is to achieve meaningful health benefits for the UK population by reducing harm and inequalities from the consumption of unhealthy commodities over the next five years and beyond

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

On the progenitor of binary neutron star merger GW170817

On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ∼40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ∼2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr

Parasitoids of the painted apple moth Teia anartoides Walker (Lepidoptera: Lymantriidae) in Australia.

Painted apple moth Teia anartoides Walker (Lepidoptera: Lymantriidae), a native to Australia, was discovered in Auckland, New Zealand in late 1999 and eradicated by 2006. It was recognised in 2002 that biological control would be the most effective long-term control strategy if eradication was unsuccessful, and a search was initiated for potential biocontrol agents in Australia. In 2003, autumn and spring surveys were undertaken in Victoria, Tasmania and South Australia of the guild of parasitoid natural enemies of T. anartoides. Eggs, larvae and pupae were collected and held to rear out any parasitoids. In addition, localised searches were made in Queensland in late 2003 early 2004 and laboratory-reared juvenile stages of T. anartoides were released for recapture in both Victoria and Queensland. Acacia dealbata Link (Fabales: Fabaceae) was the main plant from which T. anartoides was recovered, followed by apple. Most T. anartoides samples were collected from Victoria and Tasmania. Eighteen species from 13 genera of egg, larval and pupal parasitoids were reared and included Diptera (Tachinidae) and Hymenoptera (Braconidae, Encyrtidae, Eulophidae and Ichneumonidae). Of the seven Hymenopteran genera recovered from the larval stage, the most common in Victoria and Tasmania was a previously unidentified larval parasitoid Cotesia Cameron (Hymenoptera: Braconidae) sp. Echthromorpha intricatoria (Fabricius) (Hymenoptera: Ichneumonidae) was the dominant pupal parasitoid. The survey showed that the parasitoid complex associated with T anartoides is structurally very similar to that on other pest Lymantriidae in the northern hemisphere such as gypsy moth (Lymantria dispar L.) (Lepidoptera: Lymantriidae). Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae) was recorded for the first time in Australia

Fault architecture, basin structure and evolution of the Gulf of Corinth Rift, central Greece

The style of extension and strain distribution during the early stages of intra-continental rifting is important for understanding rift-margin development and can provide constraints for lithospheric deformation mechanisms. The Corinth rift in central Greece is one of the few rifts to have experienced a short extensional history without subsequent overprinting. We synthesise existing seismic reflection data throughout the active offshore Gulf of Corinth Basin to investigate fault activity history and the spatio-temporal evolution of the basin, producing for the first time basement depth and syn-rift sediment isopachs throughout the offshore rift. A major basin-wide unconformity surface with an age estimated from sea-level cycles at ca. 0.4Ma separates distinct seismic stratigraphic units. Assuming that sedimentation rates are on average consistent, the present rift formed at 1^2Ma, with no clear evidence for along-strike propagation of the rift axis. The rift has undergone major changes in relative fault activity and basin geometry during its short history. The basement depth is greatest in the central rift (maximum 3 km) and decreases to the east and west. In detail however, two separated depocentres 20^50 km long were created controlled by N- and S-dipping faults before 0.4Ma, while since ca. 0.4Ma a single depocentre (80 km long) has been controlled by several connected N-dipping faults, with maximum subsidence focused between the two older depocentres. Thus isolated but nearby faults can persist for timescales ca.1Ma and form major basins before becoming linked. There is a general evolution towards a dominance of N-dipping faults; however, in the western Gulf strain is distributed across several active N- and S-dipping faults throughout rift history, producing a more complex basin geometry

Corinth Rift margin uplift: new evidence from Late Quaternary marine shorelines

New evidence for uplift of the southern margin to the Corinth rift, one of the world's most rapidly extending continental regions, defines an area of uniform uplift separating a more rapidly uplifting western rift flank from a slowly backtilting eastern flank. This major tectonic boundary coincides with geophysical evidence for a junction between flat underlying subducted oceanic plate and steep subduction. We propose that trench rollback by the Anatolian plate over the subducting African plate has led to differential uplift and possible migration of active faulting at the southern rift margin in the last few million years