The legal and social management of psychopaths

Psychopathy has been a cause for disquiet for many years and has received more attention in recent years. Questions regarding its validity as a mental disorder, its effects on moral agency and the management of individuals suffering from the disorder have been hard to answer. This thesis first seeks to define psychopathy and establish its status as a valid mental disorder. If psychopathy is a mental disorder, rather than a behavioural construct, it must give rise to certain questions of management. Various claims concerning the responsibility and moral agency of psychopaths are considered, concluding that the psychological formation of psychopathy negates moral agency. The thesis then asks whether the disorder of psychopathy predicts recidivism, both general and violent, and whether such prediction is геliable. Evaluation of the evidence suggests that psychopathy is a valid and reliable risk factor. Management is therefore considered essential, whether civil or criminal. Mental health management of psychopaths in England and Wales is examined, discussing both current law and proposed reforms. It is found that psychopathy is currently an untreatable disorder, making civil management contentious. Criminal justice management in England and Wales is then examined, notwithstanding the claim of psychopathic irresponsibility. It is recommended that psychopaths be confined indefinitely, for the protection of the public, in conditions superior to those offered in most institutions. It is advocated that research into the treatment of psychopathy continues with the hope of establishing successful programs

A Spectacular Hα\alpha Complex in Virgo: Evidence for a Collision Between M86 and NGC 4438 and Implications for Collisional ISM Heating of Ellipticals

Deep wide-field H$\alpha$+[NII] imaging around the Virgo cluster giant elliptical galaxy M86 reveals a highly complex and disturbed ISM/ICM. The most striking feature is a set of H$\alpha$ filaments which clearly connect M86 with the nearby disturbed spiral NGC 4438 (23$'$=120 kpc projected away), providing strong evidence for a previously unrecognized collision between them. Spectroscopy of selected regions show a fairly smooth velocity gradient between M86 and NGC 4438, consistent with the collision scenario. Such a collision would impart significant energy into the ISM of M86, probably heating the gas and acting to prevent the gas from cooling to form stars. We propose that cool gas stripped from NGC 4438 during the collision and deposited in its wake is heated by shocks, ram pressure drag, or thermal conduction, producing most of the H$\alpha$ filaments. Some H$\alpha$ filaments are associated with the well-known ridge of bright X-ray emission to the NW of the nucleus, suggesting that the collision is responsible for peculiarities of M86 previously ascribed to other effects. M86 is radio-quiet, thus AGN heating is unlikely to play a significant role. The M86 system has implications for understanding the role of gravitational interactions in the heating of the ISM in ellipticals, and how collisions in clusters transform galaxies.Comment: 6 pages, 2 figures. For high-resolution images, see http://www.astro.yale.edu/tal/research/index.htm

Gene Expression Profiles Distinguish the Carcinogenic Effects of Aristolochic Acid in Target (Kidney) and Non-target (Liver) Tissues in Rats

BACKGROUND: Aristolochic acid (AA) is the active component of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. AA, however, induced nephropathy and urothelial cancer in people and malignant tumors in the kidney and urinary tract of rodents. Although AA is bioactivated in both kidney and liver, it only induces tumors in kidney. To evaluate whether microarray analysis can be used for distinguishing the tissue-specific carcinogenicity of AA, we examined gene expression profiles in kidney and liver of rats treated with carcinogenic doses of AA. RESULTS: Microarray analysis was performed using the Rat Genome Survey Microarray and data analysis was carried out within ArrayTrack software. Principal components analysis and hierarchical cluster analysis of the expression profiles showed that samples were grouped together according to the tissues and treatments. The gene expression profiles were significantly altered by AA treatment in both kidney and liver (p < 0.01; fold change > 1.5). Functional analysis with Ingenuity Pathways Analysis showed that there were many more significantly altered genes involved in cancer-related pathways in kidney than in liver. Also, analysis with Gene Ontology for Functional Analysis (GOFFA) software indicated that the biological processes related to defense response, apoptosis and immune response were significantly altered by AA exposure in kidney, but not in liver. CONCLUSION: Our results suggest that microarray analysis is a useful tool for detecting AA exposure; that analysis of the gene expression profiles can define the differential responses to toxicity and carcinogenicity of AA from kidney and liver; and that significant alteration of genes associated with defense response, apoptosis and immune response in kidney, but not in liver, may be responsible for the tissue-specific toxicity and carcinogenicity of AA

Wide-Field Precision Kinematics of the M87 Globular Cluster System

We present the most extensive combined photometric and spectroscopic study to date of the enormous globular cluster (GC) system around M87, the central giant elliptical galaxy in the nearby Virgo cluster. Using observations from DEIMOS and LRIS at Keck, and Hectospec on the MMT, we derive new, precise radial velocities for 451 GCs around M87, with projected radii from ~ 5 to 185 kpc. We combine these measurements with literature data for a total sample of 737 objects, which we use for a re-examination of the kinematics of the GC system of M87. The velocities are analyzed in the context of archival wide-field photometry and a novel Hubble Space Telescope catalog of half-light radii, which includes sizes for 344 spectroscopically confirmed clusters. We use this unique catalog to identify 18 new candidate ultra-compact dwarfs, and to help clarify the relationship between these objects and true GCs. We find much lower values for the outer velocity dispersion and rotation of the GC system than in earlier papers, and also differ from previous work in seeing no evidence for a transition in the inner halo to a potential dominated by the Virgo cluster, nor for a truncation of the stellar halo. We find little kinematical evidence for an intergalactic GC population. Aided by the precision of the new velocity measurements, we see significant evidence for kinematical substructure over a wide range of radii, indicating that M87 is in active assembly. A simple, scale-free analysis finds less dark matter within ~85 kpc than in other recent work, reducing the tension between X-ray and optical results. In general, out to a projected radius of ~ 150 kpc, our data are consistent with the notion that M87 is not dynamically coupled to the Virgo cluster; the core of Virgo may be in the earliest stages of assembly.Comment: 47 pages, ApJS in press. Redacted long data tables available on reques

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.</p

Beyond the Imitation Game: Quantifying and extrapolating the capabilities of language models

Language models demonstrate both quantitative improvement and new qualitative capabilities with increasing scale. Despite their potentially transformative impact, these new capabilities are as yet poorly characterized. In order to inform future research, prepare for disruptive new model capabilities, and ameliorate socially harmful effects, it is vital that we understand the present and near-future capabilities and limitations of language models. To address this challenge, we introduce the Beyond the Imitation Game benchmark (BIG- bench). BIG-bench currently consists of 204 tasks, contributed by 450 authors across 132 institutions. Task topics are diverse, drawing problems from linguistics, childhood develop- ment, math, common-sense reasoning, biology, physics, social bias, software development, and beyond. BIG-bench focuses on tasks that are believed to be beyond the capabilities of current language models. We evaluate the behavior of OpenAI's GPT models, Google- internal dense transformer architectures, and Switch-style sparse transformers on BIG-bench, across model sizes spanning millions to hundreds of billions of parameters. In addition, a team of human expert raters performed all tasks in order to provide a strong baseline. Findings include: model performance and calibration both improve with scale, but are poor in absolute terms (and when compared with rater performance); performance is remarkably similar across model classes, though with benefits from sparsity; tasks that improve gradually and predictably commonly involve a large knowledge or memorization component, whereas tasks that exhibit "breakthrough" behavior at a critical scale often involve multiple steps or components, or brittle metrics; social bias typically increases with scale in settings with ambiguous context, but this can be improved with prompting

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

The Ages of Passive Galaxies in a z = 1.62 Protocluster

We present a study of the relation between galaxy stellar age and mass for 14 members of the $z=1.62$ protocluster IRC 0218, using multiband imaging and HST G102 and G141 grism spectroscopy. Using $UVJ$ colors to separate galaxies into star forming and quiescent populations, we find that at stellar masses $M_* \geq 10^{10.85} M_{\odot}$, the quiescent fraction in the protocluster is $f_Q=1.0^{+0.00}_{-0.37}$, consistent with a $\sim 2\times$ enhancement relative to the field value, $f_Q=0.45^{+0.03}_{-0.03}$. At masses $10^{10.2} M_{\odot} \leq M_* \leq 10^{10.85} M_{\odot}$, $f_Q$ in the cluster is $f_Q=0.40^{+0.20}_{-0.18}$, consistent with the field value of $f_Q=0.28^{+0.02}_{-0.02}$. Using galaxy $D_{n}(4000)$ values derived from the G102 spectroscopy, we find no relation between galaxy stellar age and mass. These results may reflect the impact of merger-driven mass redistribution, which is plausible as this cluster is known to host many dry mergers. Alternately, they may imply that the trend in $f_Q$ in IRC 0218 was imprinted over a short timescale in the protocluster's assembly history. Comparing our results with those of other high-redshift studies and studies of clusters at $z\sim 1$, we determine that our observed relation between $f_Q$ and stellar mass only mildly evolves between $z\sim 1.6$ and $z \sim 1$, and only at stellar masses $M_* \leq 10^{10.85} M_{\odot}$. Both the $z\sim 1$ and $z\sim 1.6$ results are in agreement that the red sequence in dense environments was already populated at high redshift, $z \ge 3$, placing constraints on the mechanism(s) responsible for quenching in dense environments at $z\ge 1.5$Comment: 17 pages, 8 figures, 3 tables. Accepted for publication in Ap