Constraining the provenance of the Stonehenge 'Altar Stone': Evidence from automated mineralogy and U–Pb zircon age dating

The Altar Stone at Stonehenge is a greenish sandstone thought to be of Late Silurian-Devonian (‘Old Red Sandstone’) age. It is classed as one of the bluestone lithologies which are considered to be exotic to the Salisbury Plain environ, most of which are derived from the Mynydd Preseli, in west Wales. However, no Old Red Sandstone rocks crop out in the Preseli; instead a source in the Lower Old Red Sandstone Cosheston Subgroup at Mill Bay to the south of the Preseli, has been proposed. More recently, on the basis of detailed petrography, a source for the Altar Stone much further to the east, towards the Wales-England border, has been suggested. Quantitative analyses presented here compare mineralogical data from proposed Stonehenge Altar Stone debris with samples from Milford Haven at Mill Bay, as well as with a second sandstone type found at Stonehenge which is Lower Palaeozoic in age. The Altar Stone samples have contrasting modal mineralogies to the other two sandstone types, especially in relation to the percentages of its calcite, kaolinite and barite cements. Further differences between the Altar Stone sandstone and the Cosheston Subgroup sandstone are seen when their contained zircons are compared, showing differing morphologies and U-Pb age dates having contrasting populations. These data confirm that Mill Bay is not the source of the Altar Stone with the abundance of kaolinite in the Altar Stone sample suggesting a source further east, towards the Wales-England border. The disassociation of the Altar Stone and Milford Haven undermines the hypothesis that the bluestones, including the Altar Stone, were transported from west Wales by sea up the Bristol Channel and adds further credence to a totally land-based route, possibly along a natural routeway leading from west Wales to the Severn estuary and beyond. This route may well have been significant in prehistory, raising the possibility that the Altar Stone was added en route to the assemblage of Preseli bluestones taken to Stonehenge around or shortly before 3000 BC. Recent strontium isotope analysis of human and animal bones from Stonehenge, dating to the beginning of its first construction stage around 3000 BC, are consistent with the suggestion of connectivity between this western region of Britain and Salisbury Plain.This study appears to be the first application of quantitative automated mineralogy in the provenancing of archaeological lithic material and highlights the potential value of automated mineralogy in archaeological provenancing investigations, especially when combined with complementary techniques, in the present case zircon age dating

Self-Optimising Reactive Extractions: Towards the Efficient Development of Multi-Step Continuous Flow Processes

Downstream purification of products and intermediates is essential for the development of continuous flow processes. Described herein, is a study on the use of a modular and reconfigurable continuous flow platform for the self-optimisation of reactive extractions and multi-step reaction-extraction processes. The selective extraction of one amine from a mixture of two similar amines was achieved with an optimum separation of 90%, and in this case, the black-box optimisation approach was superior to global polynomial modelling. Furthermore, this methodology was utilised to simultaneously optimise the continuous flow synthesis and work-up of N-benzyl-α-methylbenzylamine with respect to four variables, resulting in a significantly improved purity

Towards Subject and Diagnostic Identifiability in the Alzheimer’s Disease Spectrum Based on Functional Connectomes

Alzheimer’s disease (AD) is the only major cause of mortality in the world without an effective disease modifying treatment. Evidence supporting the so called “disconnection hypothesis” suggests that functional connectivity biomarkers may have clinical potential for early detection of AD. However, known issues with low test-retest reliability and signal to noise in functional connectivity may prevent accuracy and subsequent predictive capacity. We validate the utility of a novel principal component based diagnostic identifiability framework to increase separation in functional connectivity across the Alzheimer’s spectrum by identifying and reconstructing FC using only AD sensitive components or connectivity modes. We show that this framework (1) increases test-retest correspondence and (2) allows for better separation, in functional connectivity, of diagnostic groups both at the whole brain and individual resting state network level. Finally, we evaluate a posteriori the association between connectivity mode weights with longitudinal neurocognitive outcomes

Effect of Biodiversity Changes in Disease Risk: Exploring Disease Emergence in a Plant-Virus System

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Can mid-regional pro-adrenomedullin (MR-proADM) increase the prognostic accuracy of NEWS in predicting deterioration in patients admitted to hospital with mild to moderately severe illness? A prospective single-centre observational study

Objective: To assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people. Design: Prospective observational study. Setting: The Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle. Participants: 300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge. Outcome measure: The primary outcome measure was the proportion of patients who, within 72 hours, had an acuity increase, defined as any combination of an increase of at least 2 in the NEWS; transfer to a higher-dependency bed or monitored area; death; or for those discharged from hospital, readmission for medical reasons. Results: NEWS and MR-proADM together predicted acuity increase more accurately than NEWS alone, increasing the area under the curve (AUC) to 0.61 (95% CI 0.54 to 0.69) from 0.55 (95% CI 0.48 to 0.62). When the confounding effects of presence of chronic obstructive pulmonary disease or heart failure and interaction with MR-proADM were included, the prognostic accuracy further increased the AUC to 0.69 (95% CI 0.63 to 0.76). Conclusions: MR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy

Repeated exposure to socioeconomic disadvantage and health selection as life course pathways to mid-life depressive and anxiety disorders

The biomedical examination was funded by Medical Research Council [G0000934], awarded under the Health of the Public initiative. Charlotte Clark is supported by an Engineering and Physical Sciences Research Fellowship. Bryan Rodgers is supported by Research Fellowships Nos 148948 and 366758 and by Program Grant No. 179805 from the National Health and Medical Research Council of Australia. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions