52 research outputs found

    Drugs and Criminal Responsibility

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    This Special Project has carried out three broad purposes.First, it has synthesized and organized materials concerning drugs and criminal responsibility into a useful guide for legal practitioners and others interested in the problems of the drug dependent defendant. Second, it has identified serious analytical flaws in many of the defenses available to the criminal defendant. Finally,it has responded to these deficiencies with proposals intended to protect not only the legal rights of the drug dependent defendant but also the rights of society pertaining to criminal justice. While these societal interests include the swift imposition of criminal penalties when warranted, they should not be allowed to diminish the concomitant rights of the criminal defendant. In fact, societal rights would be better served by a reexamination and reinterpretation of several traditional legal theories concerning drugs and criminal defendants. A recognition by courts and legislatures of the existing analytical flaws should lead to the development of more equitable theories and a search for alternative forms of treatment and rehabilitation for the drug dependent defendant. Rather than hiding behind the guise of legal history and moral judgment, courts and legislatures should respond to illogical and insufficient theories that fail to deal with the drug dependent defendant in an equitable and just manner

    Extracting Relevance and Affect Information from Physiological Text Annotation

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    We present physiological text annotation, which refers to the practice of associating physiological responses to text content in order to infer characteristics of the user information needs and affective responses. Text annotation is a laborious task, and implicit feedback has been studied as a way to collect annotations without requiring any explicit action from the user. Previous work has explored behavioral signals, such as clicks or dwell time to automatically infer annotations, and physiological signals have mostly been explored for image or video content. We report on two experiments in which physiological text annotation is studied first to 1) indicate perceived relevance and then to 2) indicate affective responses of the users. The first experiment tackles the user’s perception of relevance of an information item, which is fundamental towards revealing the user’s information needs. The second experiment is then aimed at revealing the user’s affective responses towards a -relevant- text document. Results show that physiological user signals are associated with relevance and affect. In particular, electrodermal activity (EDA) was found to be different when users read relevant content than when they read irrelevant content and was found to be lower when reading texts with negative emotional content than when reading texts with neutral content. Together, the experiments show that physiological text annotation can provide valuable implicit inputs for personalized systems. We discuss how our findings help design personalized systems that can annotate digital content using human physiology without the need for any explicit user interaction

    Can Hardcore Actualism Validate S5?

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    Hardcore actualism (HA) grounds all modal truths in the concrete constituents of the actual world (see, e.g., Borghini and Williams (2008), Jacobs (2010), Vetter (2015)). I bolster HA, and elucidate the very nature of possibility (and necessity) according to HA, by considering if it can validate S5 modal logic. Interestingly, different considerations pull in different directions on this issue. To resolve the tension, we are forced to think hard about the nature of the hardcore actualist's modal reality and how radically this departs from possible worlds orthodoxy. Once we achieve this departure, the prospects of a hardcore actualist validation of S5 look considerably brighter. This paper thus strengthens hardcore actualism by arguing that it can indeed validate S5–arguably the most popular logic of metaphysical modality–and, in the process, it elucidates the very nature of modality according to this revisionary, but very attractive, modal metaphysics

    Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

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    Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

    GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

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    Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

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    Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

    Get PDF
    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

    John Brown.

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    A collection of articles, pamphlets, newspaper clippings, drawings and photographs relating to John Brown's raid at Harpers Ferry.Extra illustrated.Binder's spine title.Luke F. Parsons [obituary] -- John Brown at Harper's Ferry : the fight at the engine room, as seen by one of his prisoners -- The last letter of John Brown / by Charles H. Small -- Recollections of the John Brown raid / by a Virginian who witnessed the fight -- The raid of John Brown at Harper's Ferry as I saw it / Samuel Vanderlip Leech.A collection of articles, pamphlets, newspaper clippings, drawings and photographs relating to John Brown's raid at Harpers Ferry.Mode of access: Internet
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