Radio Emission from SN 1994I in NGC 5194 (M 51) - The Best Studied Type Ib/c Radio Supernova

We present the results of detailed monitoring of the radio emission from the Type Ic supernova SN 1994I from 3 days after optical discovery on 1994 March 31 until eight years later at age 2927 days on 2002 April 05. The data were mainly obtained using the Very Large Array at the five wavelengths, 1.3, 2.0, 3.6, 6.2, and 21 cm, and from the Cambridge 5 km Ryle Telescope at 2.0 cm. Two additional measurements were obtained at millimeter wavelengths. This data set represents the most complete, multifrequency radio observations ever obtained for a Type Ib/c supernova. The radio emission evolves regularly in both time and frequency and is well described by established SN emission/absorption models. It is the first radio supernova with sufficient data to show that it is clearly dominated by the effects of synchrotron self-absorption at early times.Comment: 43 pages, 5 figure

Population pharmacokinetics of subcutaneous C1-inhibitor for prevention of attacks in patients with hereditary angioedema

Background: Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. Objective: To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA \uae ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics. Methods: C1-INH functional activity data obtained after administration of various C1-INH (intravenous; IV) and C1-INH (SC) doses from 1 study in healthy volunteers (n = 16) and 2 studies in subjects with HAE (n = 108) were pooled to develop a population pharmacokinetic model (NONMEM v7.2). Pharmacokinetic parameters derived from steady-state simulations based on the final model were also evaluated. Results: C1-INH functional activity following C1-INH (SC) administration was described by a linear one-compartment model with first-order absorption and elimination, with inter-individual variability in all parameters tested. The mean population bioavailability of C1-INH (SC), and pharmacokinetic parameters for clearance (CL), volume of distribution, and absorption rate were estimated to be ~43%, 1.03 mL/hour/kg, 0.05 L/kg and 0.0146 hour 121 , respectively. The effect of bodyweight on CL of C1-INH functional activity was included in the final model, estimated to be 0.74. Steady-state simulations of C1-INH functional activity vs time profiles in 1000 virtual HAE patients revealed higher minimum functional activity (C trough ) levels after twice-weekly dosing with 40 IU/kg (~40%) and 60 IU/kg (~48%) compared with 1000 IU IV (~30%). Based on the population pharmacokinetic model, the median time to peak concentration was ~59 hours and the median apparent plasma half-life was ~69 hours. Conclusions and Clinical Relevance: Twice-weekly bodyweight-adjusted dosing of C1-INH (SC) exhibits linear pharmacokinetics and dose-dependent increases in C trough levels at each dosing interval. In this analysis, SC dosing led to maintenance of higher C trough levels than IV dosing

International litigation and the dissaggregation of disputes: Ukraine/Russia as a case study

This article explores the phenomenon of ‘disaggregation’ of disputes in international law, that is, the carving up of broader disputes into discrete legal claims based on different international legal rules and subject to the jurisdiction of different international tribunals. In particular, its focus is on certain under-explored consequences of this phenomenon for the jurisdiction of international tribunals, asking whether the relationship between the specific claims and the broader dispute might affect the jurisdiction of the tribunals. Employing the ongoing Ukraine/Russia dispute, which has yielded multiple claims before different international tribunals, the article offers an original analysis of these jurisdictional questions. It presents three approaches discernible from case law where tribunals face claims over which they appear to have jurisdiction that implicate a broader dispute over which they do not. The article ends with a consideration of possible explanations for why a tribunal might follow one approach over the others in any given case

In Quest of Neutrino Masses at O{\cal{O}}(eV) Scale

Neutrino oscillation and tritium beta decay experiments taken simultaneously into account are able to access the so far imperceptible absolute neutrino masses at the electronvolt level. The neutrino mass spectrum derived in this way is independent of the nature of neutrinos (Dirac or Majorana). Furthermore, the lack of neutrinoless double beta decay gives additional constraints on the Majorana neutrino mass spectrum. A case of three neutrinos is examined. Influence of different solutions to the solar neutrino deficit problem on the results is discussed. Apart from the present situation, four qualitatively distinct experimental situations which are possible in the future are investigated: when the two decay experiments give only upper bounds on effective neutrino masses, when either one of them gives a positive result, and when both give positive results. The discussion is carried out by taking into account the present experimental errors of relevant neutrino parameters as well as their much more precise expected estimations (e.g. by $\nu$ factories). It is shown in which cases the upgraded decay experiments simultaneously with neutrino oscillation data may be able to fix the absolute scale of the neutrino mass spectrum, answer the question of the neutrino nature and put some light on CP phases in the lepton sector.Comment: 30 pages, 6 figs, to appear in PR

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Constructing an International Community

What unites states and other global actors around a shared governance project? How does the group—what I will call an “international community”—coalesce and stay engaged in the enterprise? A frequent assumption is that an international community is cemented by its members’ commonalities and depleted by their intractable disagreements. This article critiques that assumption and presents, as an alternative, a theory that accounts for the combined integration and discord that actually characterize most global governance associations. I argue that conflict, especially conflict that manifests in law, is not necessarily corrosive to an international community. To the contrary, it often is a unifying force that helps constitute and fortify the community and support the governance project. As such, international legal conflict can have systemic value for the global order, even when it lacks substantive resolution. The implications for the design and practice of international law are far-reaching

Cytologic scoring of equine exercise-induced pulmonary hemorrhage : performance of human experts and a deep learning-based algorithm

Exercise-induced pulmonary hemorrhage (EIPH) is a relevant respiratory disease in sport horses, which can be diagnosed by examination of bronchoalveolar lavage fluid (BALF) cells using the total hemosiderin score (THS). The aim of this study was to evaluate the diagnostic accuracy and reproducibility of annotators and to validate a deep learning-based algorithm for the THS. Digitized cytological specimens stained for iron were prepared from 52 equine BALF samples. Ten annotators produced a THS for each slide according to published methods. The reference methods for comparing annotator’s and algorithmic performance included a ground truth dataset, the mean annotators’ THSs, and chemical iron measurements. Results of the study showed that annotators had marked interobserver variability of the THS, which was mostly due to a systematic error between annotators in grading the intracytoplasmatic hemosiderin content of individual macrophages. Regarding overall measurement error between the annotators, 87.7% of the variance could be reduced by using standardized grades based on the ground truth. The algorithm was highly consistent with the ground truth in assigning hemosiderin grades. Compared with the ground truth THS, annotators had an accuracy of diagnosing EIPH (THS of < or ≥ 75) of 75.7%, whereas, the algorithm had an accuracy of 92.3% with no relevant differences in correlation with chemical iron measurements. The results show that deep learning-based algorithms are useful for improving reproducibility and routine applicability of the THS. For THS by experts, a diagnostic uncertainty interval of 40 to 110 is proposed. THSs within this interval have insufficient reproducibility regarding the EIPH diagnosis.The Dres. Jutta and Georg Bruns-Stifung für innovative Veterinärmedizin.https://journals.sagepub.com/home/vetCompanion Animal Clinical Studie