THE SUBJECT OF SOVEREIGNTY: LAW, POLITICS AND MORAL REASONING IN HUGO GROTIUS

AbstractHugo Grotius’s account of sovereign power inDe iure belli ac pacisoccupies a contested place in recent genealogies of modern sovereignty. This article takes a fresh approach by arguing that Grotius’s legal arguments do not do their work alone. They function within a broader horizon of what he calls “morals,” a field of reasoning that has debts to scholastic moral theology and Aristotelian moral science. Grotius's conception of sovereignty represents a modulation between law and “morals,” which allows him both to separate his scientific jurisprudence from the science of politics and nevertheless to reply to the political scientists on their own ground. The context of “morals,” however, is not narrowly political but inter-political, generating a potential tension between popular aspirations to sovereignty and the international order. Grotius’s “moral” handling of the issue offers an invitation to reflect on our current preoccupation with much the same concerns.</jats:p

The space of politics and the space of war in Hugo Grotius’s<i>De iure belli ac pacis</i>

Despite the currency of the ‘spatial turn’ in history more generally, the history of political thought has not yet turned its attention to the concept of space in any systematic way. The natural rights tradition seems particularly resistant to such a reading. The present article seeks to uncover how notions of space and spatial relations intersect with law and legal relations in a key text of that tradition. I argue that space is central to the way in which Grotius in De iure belli ac pacis understands political and inter-political phenomena and that his concept of moral reasoning is specifically geared to accommodate this dimension.This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/23801883.2016.122817

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations.Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis.Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed.Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity.Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems

Inotersen treatment for patients with hereditary transthyretin amyloidosis

BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin. METHODS: We conducted an international, randomized, double-blind, placebo-controlled, 15-month, phase 3 trial of inotersen in adults with stage 1 (patient is ambulatory) or stage 2 (patient is ambulatory with assistance) hereditary transthyretin amyloidosis with polyneuropathy. Patients were randomly assigned, in a 2:1 ratio, to receive weekly subcutaneous injections of inotersen (300 mg) or placebo. The primary end points were the change in the modified Neuropathy Impairment Score+7 (mNIS+7; range, -22.3 to 346.3, with higher scores indicating poorer function; minimal clinically meaningful change, 2 points) and the change in the score on the patient-reported Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating poorer quality of life). A decrease in scores indicated improvement. RESULTS: A total of 172 patients (112 in the inotersen group and 60 in the placebo group) received at least one dose of a trial regimen, and 139 (81%) completed the intervention period. Both primary efficacy assessments favored inotersen: the difference in the least-squares mean change from baseline to week 66 between the two groups (inotersen minus placebo) was -19.7 points (95% confidence interval [CI], -26.4 to -13.0; P<0.001) for the mNIS+7 and -11.7 points (95% CI, -18.3 to -5.1; P<0.001) for the Norfolk QOL-DN score. These improvements were independent of disease stage, mutation type, or the presence of cardiomyopathy. There were five deaths in the inotersen group and none in the placebo group. The most frequent serious adverse events in the inotersen group were glomerulonephritis (in 3 patients [3%]) and thrombocytopenia (in 3 patients [3%]), with one death associated with one of the cases of grade 4 thrombocytopenia. Thereafter, all patients received enhanced monitoring. CONCLUSIONS: Inotersen improved the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis. Thrombocytopenia and glomerulonephritis were managed with enhanced monitoring. (Funded by Ionis Pharmaceuticals; NEURO-TTR ClinicalTrials.gov number, NCT01737398 .)

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Use, War, and Commercial Society. Changing Paradigms of Human Relations with Animals in the Early Modern Law of Nature and of Nations

Abstract The ideas of a human war on nature, and a human war on animals more specifically, are now current in international politics and international law. This article unearths a historical understanding of war on animals as one paradigm of human relations with animals in the early modern law of nature and of nations (16th to 18th centuries). It shows how dominium (property or mastery) over animals was placed at the origin of all human dominium, and was in consequence conceptually central to its legitimation. It also shows, however, that dominium over animals was not straightforward to justify, because, although they were not human beings, they were seen as sufficiently like human beings in sentience to resist being legally treated like plants or inanimate objects. This article tracks three successive paradigms, all of all of which involve conceptual tensions that are illuminating for current thinking concerning violence against animals.</jats:p

The ancient notion of self-preservation in the theories of Hobbes and Spinoza

Over the course of four sections this PhD examines the ways in which the Aristotelian, Stoic and Epicurean philosophers portray bodily activity. In particular, it argues that their claims regarding bodies' natural tendency to preserve themselves, and seek out the goods capable of promoting their well-being, came to influence Hobbes's and Spinoza's later accounts of natural, animal and social behaviour. The first section presents the ancient accounts of natural and animal bodily tendencies and explores the specific ways in which the Aristotelian, Stoic and Epicurean views on animal desires came to complement and diverge from each other. After investigating the perceived links between natural philosophy, psychology and ethics, the section proceeds to consider how the ancients used this 'unified' view of nature to guide their accounts of the soul's primary appetites and desires. Also examined is the extent to which civil society is portrayed as a means of securing the individual against others, and how Aristotelian philia, Theophrastian oikeiotês and Stoic oikeiōsis came to stand in opposition to the fear-driven and compact-based accounts of social formation favoured by the Epicureans. The second section considers how the ancient accounts of impulsive behaviour and social formation were received and diffused via new editions of ancient texts, eclectic readings of Aristotle, and the attempts of Neostoic and Neoepicurean authors to update and systematise those philosophies from the late sixteenth century onwards. The particular treatments of Hellenistic thought by authors such as Justus Lipsius, Hugo Grotius and Pierre Gassendi are considered in detail and are placed within the context of the growing trend to use Stoic and Epicurean thought to replace the authority of Aristotle in the areas of science, psychology, and politics. The final two sections are devoted respectively to considering the ways in which Hobbes and Spinoza encountered the Hellenistic accounts of bodies and demonstrating how these earlier accounts came to feature in each of their own discussions of bodily tendencies. Engaging with a wide range of their texts, each section develops the many nuances and contours that emerged as both writers developed and fine-tuned their accounts of bodily actions. This reveals the many ways in which the ancient accounts of self-preservation helped to unify large aspects of Hobbes's and Spinoza's own philosophical corpus, while equally showing how a well-developed account of bodily tendencies might challenge the scholastic worldview and expand further the boundaries of the so-called 'New Science'.EThOS - Electronic Theses Online ServiceGBUnited Kingdo