Aspects of discontinuous precipitation reactions in Ag-7.5Cu

Since the crystallographic orientation of a cellular colony derives from the grain it grows away from, experimental interest in discontinuous precipitation (DP) has centred on how nucleation and growth rates are affected by the misorientation of the initiating grain boundary. There has been little attention paid to the nature of the interface at the reaction front. Ageing experiments on Ag-7.5Cu at 2500C showed there to be two DP colony populations with distinctly different growth behaviours. EBSD studies have shown that as the colonies grow there is a build-up of misorientation behind the reaction front and eventually the fast growing colonies are surrounded by interfaces close to particular low Σ coincident site lattice (CSL) misorientations with respect to the grain into which they are growing. On the other hand, slow growing colonies are characterised by misorientations close to a different set of low ΣCSLs. The growth mechanisms behind this behaviour will be discussed

Microstructures of ancient and historic silver

The microstructures of silver-copper alloys from archaeological and historical contexts have been of particular interest since age-related changes at grain boundaries were first mooted as an indicator of antiquity and authenticity. Subsequent discussion has focused on how such structures might be reproduced by appropriate heat treatments but there was only limited experimental investigation of these precipitation phenomena. A second strand of interest has been the embrittlement of archaeological silver by segregation of impurities to grain boundaries. More recently industrial interest has developed in silver-copper alloys because of their use as solders and in electrical contact, and a growing number of papers on sterling and other silver alloy microstructures is being published. To interpret the microstructures of ancient and historic silver the key question is how to distinguish between the respective contributions of manufacture, age and the environment. This paper will describe and discuss a series of heat treatment experiments on wrought Britannia and Sterling silver and also on cast Sterling, the microstructure of cast silver being hitherto a rather neglected topic. The simple eutectic silver-copper system can exhibit a variety of precipitate morphologies and these have been characterised using optical microscopy, scanning and transmission electron microscopy, electron backscatter diffraction, and microhardness and nanoindenter testing. As a test case for discriminating between the effects of manufacture and age a series of medieval Islamic silver coins with a range of mint technologies has been examined in detail and the results presented here. The data will also be used to highlight the limits within which age-related modifications of the microstructure can be expected to be observed

Spatially resolved texture analysis of Napoleonic War era copper bolts

The spatial resolution achievable by a time-of-flight neutron strain scanner has been harnessed using a new data analysis methodology (NyRTex) to determine, nondestructively, the spatial variation of crystallographic texture in objects of cultural heritage. Previous studies on the crystallographic texture at the centre of three Napoleonic War era copper bolts, which demonstrated the value of this technique in differentiating between the different production processes of the different types of bolts, were extended to four copper bolts from the wrecks of HMS Impregnable (completed 1786), HMS Amethyst (1799), HMS Pomone (1805) and HMS Maeander (1840) along with a cylindrical `segment' of a further incomplete bolt from HMS Pomone. These included bolts with works stamps, allowing comparison with documentary accounts of the manufacturing processes used, and the results demonstrated unequivocally that bolts with a `Westwood and Collins' patent stamp were made using the Collins rather than the Westwood process. In some bolts there was a pronounced variation in texture across the cross section. In some cases this is consistent with what is known of the types of hot and cold working used, but the results from the latest study might also suggest that, even in the mature phase of this technology, some hand finishing was sometimes necessary. This examination of bolts from a wider range of dates is an important step in increasing our understanding of the introduction and evolution of copper fastenings in Royal Navy warships

Gristhorpe Man: an Early Bronze Age log-coffin burial scientifically defined

© 2010 Antiquity PublicationsA log-coffin excavated in the early nineteenth century proved to be well enough preserved in the early twenty-first century for the fill armoury of modern scientific investigation to give its occupants and contents new identity, new origins and a new date. In many ways the interpretation is much the same as before: a local big man buried looking out to sea. Modern analytical techniques can create a person more real, more human and more securely anchored in history. This research team shows how.The project has been funded by grants from the British Academy, British Association for the Advancement of Science, Natural Environment Research Council, Royal Archaeological Institute and Scarborough Museums Trust. CJK’s participation in this project was funded by a Leverhulme Research Fellowship (RF/6/RFG/2008/0253)

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes