368 research outputs found
Enforceable duties: Cicero and Kant on the legal nature of political order
This article seeks to show the importance of Cicero for Kant by pointing out the systematic relationship between their respective views on ethics and law. Cicero was important to Kant because Cicero had already elaborated an imperative, âquasi-juralâ conception of duty or obligation. Cicero had also already prefigured the distinction between ethical duties and duties of justice. The article does not establish any direct historical influence, but points out interesting systematic overlaps. The most important in the realm of ethics are a universal rationalism; a rule-based normative framework of duty; and skepticism about (Cicero), or rejection of (Kant), eudaimonism. In the realm of political theory, it is the centrality of law and of property that unites both thinkers; both reject voluntarism in thinking that consensus flows from the right external laws, not the other way around, and thus creates a juridical community; and lastly, both Cicero and Kant believe that transparence, or publicity, is a key ideal that might be presupposed by both the ethical and the juridical domain. The article thus shows that both Cicero and Kant separate ethics from law, but there are indications that neither has given up the aspiration to bridge the two realms on a higher plane. This reading of Kant yields both a more Ciceronian Kant and allows us to perceive Kantian aspects of Cicero
Thucydides, Hobbes, and the Melian Dialogue
Thucydides and Hobbes are often interpreted as ârealistsâ. States vis-Ă -vis each other remain in the state of nature and are conceptualized in analogy with individuals in the state of nature. States are therefore seen as engaging in the kind of self-interested behavior that makes cooperation elusive. In this chapter I argue that Thucydidesâs Melian Dialogue might have shown Hobbes that the analogy between individuals and states does not really go all the way. For Hobbes, states are the artificial structures within which individuals may satisfy their subjective desires; once the Melian commonwealth could no longer guarantee its citizensâ safety, it would have been rational for the Melians to surrender, rather than risk an overwhelmingly probable catastrophe. States and individuals are also distinct in that the former may develop better knowledge of the laws of nature than individuals ever could. This fissure in the individual-state analogy is the lesson Hobbes drew from the Melian Dialogue, as can be seen in his analysis of sovereignty by acquisition in the Leviathan. Thucydides was important because his history, Hobbes thought, was true and could therefore provide useful examples of reason and its defects in action; the Melians might thus in addition have provided an illustration for what Hobbes believed was wrong with the Fooleâs reasoning. Accordingly, Thucydides can be seen to have provided a foundation for Hobbesâs argument for peace and individual self-preservation
On the liberties of the ancients: licentiousness, equal rights, and the rule of law
In this article, we discuss Greek and Roman conceptions of liberty. The supposedly âneo-Romanâ view of liberty as non-domination is really derived from negative Greek models, we argue, while Roman authors devised an alternative understanding of liberty that rested on the equality of legal rights. In this âpaleo-Romanâ model, as long as the law was the same for all, you were free; whether or not you participated in making the law was not a constitutive feature of liberty. In essence, this Roman theory was a theory of freedom as the rule of law and the guarantee of equal rights, especially due process rights. For this Roman concept of âlegal liberty,â as we call it,political participation was neither necessary nor sufficient. Theorized by Cicero and historicized by Livy, the Roman understanding of freedom flourished in early-modern times, proving important to paradigmatic republican authors such as Machiavelli and Rousseau as well as to Hobbes, whose work we discuss as a helpful point of comparison
Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo
BACKGROUND
Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo .
METHODS
Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively.
RESULTS
THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe form, as evinced by the STXM results.
CONCLUSION
We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo
Low serum zinc levels predict presence of depression symptoms, but not overall disease outcome, regardless of ATG16L1 genotype in Crohn's disease patients.
Zinc deficiency (ZD) in Crohn's disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the prevalence of ZD in CD patients in clinical remission, its association with mood disturbances and to analyze a potential impact on future disease course.
Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years ( <i>n</i> = 47) were compared with those from patients developing complications ( <i>n</i> = 50). Baseline symptoms of depression and anxiety were measured with the Hospital Anxiety and Depression scale.
Mean zinc level in the 97 patients (40.4 ± 15.7 years, 44.3% males) was 18.0 ± 4.7 Όmol/l. While no ZD (<11 Όmol/l) was observed, we found low zinc levels (<15.1 Όmol/l) in 28 patients (28.9%). Males had higher zinc levels compared with females (19.4 ± 5.7 <i>versus</i> 16.8 ± 3.3, <i>p</i> = 0.006). Patients with low zinc levels more often reported depression symptoms compared with patients with higher levels (27.3 <i>versus</i> 9.4%, <i>p</i> = 0.047). In a multivariate analysis, zinc levels were an independent negative predictor for depression symptoms [odds ratio (OR) 0.727, 95% confidence interval (CI) 0.532-0.993, <i>p</i> = 0.045]. Zinc levels of patients with a complicated disease course were not different from those of patients without (17.7 ± 4.3 <i>versus</i> 18.3 ± 5.1, n.s.). Baseline zinc levels did not predict disease outcome regardless of ATG16L1 genotype.
Low-normal zinc levels were an independent predictor for the presence of depression symptoms in CD patients. Zinc levels at baseline did not predict a complicated disease course, neither in CD patients overall, nor ATG16L1 <sup>T300A</sup> carriers
Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.
There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD).
Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively.
A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, Pâ=â0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, Pâ=â0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, Pâ=â0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%).
In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy
Self-love and sociability: the ârudiments of commerceâ in the state of nature
Istvan Hontâs classic work on the theoretical links between the seventeenth-century natural jurists Hugo Grotius and Samuel Pufendorf and the eighteenth-century Scottish political economists remains a popular trope among intellectual and economic historians of various stamps. Despite this, a common criticism levelled at Hont remains his relative lack of engagement with the relationship between religion and economics in the early modern period. This paper challenges this aspect of Hontâs narrative by drawing attention to an alternative, albeit complementary, assessment of the natural jurisprudential heritage of eighteenth-century British political economy. Specifically, the article attempts to map on to Hontâs thesis the Christian Stoic interpretation of Grotius and Pufendorf which has gained greater currency in recent years. In doing so, the paper argues that Grotius and Pufendorfâs contributions to the âunsocial sociabilityâ debate do not necessarily lead directly to the Scottish school of political economists, as is commonly assumed. Instead, it contends that a reconsideration of Grotius and Pufendorf as neo-Stoic theorists, particularly via scrutiny of their respective adaptations of the traditional Stoic theory of oikeiosis, steers us towards the heart of the early English âclericalâ Enlightenment
Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires
The production of tt⟠, W+bb⟠and W+cc⟠is studied in the forward region of protonâproton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fbâ1 . The W bosons are reconstructed in the decays WââÎœ , where â denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of , and is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 0.02 \mbox{fb}^{-1}. The bosons are reconstructed in the decays , where denotes muon or electron, while the and quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions
Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis
Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patientsâ assessments of disease severity. We also evaluated relationships between patientsâ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings
Observation of the B0 â Ï0Ï0 decay from an amplitude analysis of B0 â (Ï+Ïâ)(Ï+Ïâ) decays
Protonâproton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fbâ1 , are analysed to search for the charmless B0âÏ0Ï0 decay. More than 600 B0â(Ï+Ïâ)(Ï+Ïâ) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0âÏ0Ï0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0âÏ0Ï0 decays yielding a longitudinally polarised final state is measured to be fL=0.745â0.058+0.048(stat)±0.034(syst) . The B0âÏ0Ï0 branching fraction, using the B0âÏKâ(892)0 decay as reference, is also reported as B(B0âÏ0Ï0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))Ă10â6
- âŠ