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Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
Field studies were conducted in 2016 and 2017 in Clinton, NC, to determine the interspecific and intraspecific interference of Palmer amaranth (Amaranthus palmeri S. Watson) or large crabgrass [Digitaria sanguinalis (L.) Scop.] in ‘Covington’ sweetpotato [Ipomoea batatas (L.) Lam.]. Amaranthus palmeri and D. sanguinalis were established 1 d after sweetpotato transplanting and maintained season-long at 0, 1, 2, 4, 8 and 0, 1, 2, 4, 16 plants m−1 of row in the presence and absence of sweetpotato, respectively. Predicted yield loss for sweetpotato was 35% to 76% for D. sanguinalis at 1 to 16 plants m−1 of row and 50% to 79% for A. palmeri at 1 to 8 plants m−1 of row. Weed dry biomass per meter of row increased linearly with increasing weed density. Individual dry biomass of A. palmeri and D. sanguinalis was not affected by weed density when grown in the presence of sweetpotato. When grown without sweetpotato, individual weed dry biomass decreased 71% and 62% from 1 to 4 plants m−1 row for A. palmeri and D. sanguinalis, respectively. Individual weed dry biomass was not affected above 4 plants m−1 row to the highest densities of 8 and 16 plants m−1 row for A. palmeri and D. sanguinalis, respectively.
Transgenic crops are being developed with herbicide resistance traits to expand innovative weed management solutions for crop producers. Soybean with traits that confer resistance to the hydroxyphenylpyruvate dioxygenase herbicide isoxaflutole is under development and will provide a novel herbicide mode of action for weed management in soybean. Ten field experiments were conducted over 2 years (2017 and 2018) on five soil textures with isoxaflutole-resistant soybean to evaluate annual weed control using one- and two-pass herbicide programs. The one-pass weed control programs included isoxaflutole plus metribuzin, applied PRE, at a low rate (52.5 + 210 g ai ha−1), medium rate (79 + 316 g ai ha−1), and high rate (105 + 420 g ai ha−1); and glyphosate applied early postemergence (EPOST) or late postemergence (LPOST). The two-pass weed control programs included isoxaflutole plus metribuzin, applied PRE, followed by glyphosate applied LPOST, and glyphosate applied EPOST followed by LPOST. At 4 weeks after the LPOST application, control of common lambsquarters, pigweed species, common ragweed, and velvetleaf was variable at 25% to 69%, 49% to 86%, and 71% to 95% at the low, medium, and high rates of isoxaflutole plus metribuzin, respectively. Isoxaflutole plus metribuzin at the low, medium, and high rates controlled grass species evaluated (i.e., barnyardgrass, foxtail, crabgrass, and witchgrass) 85% to 97%, 75% to 99%, and 86% to 100%, respectively. All two-pass weed management programs provided 98% to 100% control of all species. Weed control improved as the rate of isoxaflutole plus metribuzin increased. Two-pass programs provided excellent, full-season annual grass and broadleaf weed control in isoxaflutole-resistant soybean.
Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
We have mapped the full crystallographic orientation of sea ice using electron backscatter diffraction (EBSD). This is the first time EBSD has been used to study sea ice. Platelet ice is a feature of sea ice near ice shelves. Ice crystals accumulate as an unconsolidated sub-ice platelet layer beneath the columnar ice (CI), where they are subsumed by the advancing sea–ice interface to form incorporated platelet ice (PI). As is well known, in CI the crystal preferred orientation comprises dominantly horizontal c-axes, while PI has c-axes varying between horizontal and vertical. For the first time, this study shows the a-axes of CI and PI are not random. Misorientation analysis has been used to illuminate the possible drivers of these alignments. In CI the misorientation angle distribution from random pairs and neighbour pairs of grains are indistinguishable, indicating the distributions are a consequence of crystal preferred orientation. Geometric selection during growth will develop the a-axis alignment in CI if ice growth in water is fastest parallel to the a-axis, as has previously been hypothesised. In contrast, in PI random-pair and neighbour-pair misorientation distributions are significantly different, suggesting mechanical rotation of crystals at grain boundaries as the most likely explanation.
By the mid-twentieth century in the United Kingdom, musical instrument manufacturing had become an increasingly mechanized activity. Craft skills had been displaced in many areas, yet remained a vital source of competitive advantage in local and international markets and were particularly valued by professional musicians. This article examines the contrasting experiences of two British musical instrument manufacturers, tracing the unfolding relationship between their pursuit of entrepreneurial opportunities and capability development. Boosey & Hawkes, a large, well-established manufacturing and publishing company, was an early pioneer, while Paxman Bros., a small musical retailer, transformed itself into one of the world’s most respected specialist manufacturers. The narrative probes the factors that shaped decision making in these companies as they developed a series of design innovations for one of the more complex brass instruments: the French horn. It draws on relevant theoretical insights to examine how a dynamic interaction between opportunity and capability, coupled with unanticipated contingencies, contributed to divergent outcomes for each company.
Treatment for hoarding disorder is typically performed by mental health professionals, potentially limiting access to care in underserved areas.
We aimed to conduct a non-inferiority trial of group peer-facilitated therapy (G-PFT) and group psychologist-led cognitive–behavioural therapy (G-CBT).
We randomised 323 adults with hording disorder 15 weeks of G-PFT or 16 weeks of G-CBT and assessed at baseline, post-treatment and longitudinally (≥3 months post-treatment: mean 14.4 months, range 3–25). Predictors of treatment response were examined.
G-PFT (effect size 1.20) was as effective as G-CBT (effect size 1.21; between-group difference 1.82 points, t = −1.71, d.f. = 245, P = 0.04). More homework completion and ongoing help from family and friends resulted in lower severity scores at longitudinal follow-up (t = 2.79, d.f. = 175, P = 0.006; t = 2.89, d.f. = 175, P = 0.004).
Peer-led groups were as effective as psychologist-led groups, providing a novel treatment avenue for individuals without access to mental health professionals.
Declaration of interest
C.A.M. has received grant funding from the National Institutes of Health (NIH) and travel reimbursement and speakers’ honoraria from the Tourette Association of America (TAA), as well as honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. K.D. receives research support from the NIH and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. R.S.M. receives research support from the National Institute of Mental Health, National Institute of Aging, the Hillblom Foundation, Janssen Pharmaceuticals (research grant) and the Alzheimer's Association. R.S.M. has also received travel support from the National Institute of Mental Health for Workshop participation. J.Y.T. receives research support from the NIH, Patient-Centered Outcomes Research Institute and the California Tobacco Related Research Program, and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. All other authors report no conflicts of interest.
John Blake (1947–2016) was a leader in fluid mechanics, his two principal areas of expertise being biological fluid mechanics on microscopic scales and bubble dynamics. He produced leading research and mentored others in both Australia, his home country, and the UK, his adopted home. This article reviews John Blake’s contributions in biological fluid mechanics, as well as gives the author’s personal viewpoint as one of the many graduate students and researchers who benefitted from his supervision, guidance and inspiration. The key topics from biological mechanics discussed are: “squirmer” models of protozoa, the method of images in Stokes flow and the “blakelet” solution, discrete cilia modelling via slender body theory, physiological flows in respiration and reproduction, blinking stokeslets in microorganism feeding, human sperm motility and embryonic nodal cilia.
Combinatorial auctions enhance our ability to efficiently allocate multiple resources in complex economic environments. They explicitly allow buyers and sellers of goods and services to bid on packages of items with related values or costs. For example, “I bid $10 to buy 1 unit of item A and 2 units of item B, but I won't pay anything unless I get everything.” They also allow buyers, sellers and the auctioneer to impose logical constraints that limit the feasible set of auction allocations. For example, “I bid $12 to buy 2 units of item C OR $15 to buy 3 units of item D, but I don't want both.” Finally, they can handle functional relationships amongst bids or allocations, such as budget constraints or aggregation limits that allow many bids to be connected together. For example, “I won't spend more than a total of $35 on all my bids” or “This auction will allocate no more than a total of 7 units of items F, G and H.”
There are several reasons to prefer to have the bidding message space expanded beyond the simple space used for traditional single commodity auctions. As Bykowsky et al. (2000) point out, when values have strong complementarities, there is a danger of ‘financial exposure’ that results in losses to bidders if combinatorial bidding is not allowed. For example, in the case of complementary items such as airport take-off and landing times, the ability to reduce uncertainty to the bidder by allowing him to precisely declare his object of value, a cycle of slots for an entire daily flight pattern, is obvious: one component slot not acquired ruins the value of the flight cycle. In the same situation substitution possibilities would also be important to consider: if flight cycle A is not won, cycle B may be an appropriate though less valuable substitute for the crew and equipment available. Allocation inefficiencies due to financial exposure in noncombinatorial auctions have been frequently demonstrated in experiments beginning with Rassenti et al. (1982) (see also Porter (1999), Banks et al. (1989), Ledyard et al. (2002) and Kwasnika et al. (1998)).