Maximizing Service Reliability in Distributed Computing Systems with Random Node Failures: Theory and Implementation

In distributed computing systems (DCSs) where server nodes can fail permanently with nonzero probability, the system performance can be assessed by means of the service reliability, defined as the probability of serving all the tasks queued in the DCS before all the nodes fail. This paper presents a rigorous probabilistic framework to analytically characterize the service reliability of a DCS in the presence of communication uncertainties and stochastic topological changes due to node deletions. The framework considers a system composed of heterogeneous nodes with stochastic service and failure times and a communication network imposing random tangible delays. The framework also permits arbitrarily specified, distributed load-balancing actions to be taken by the individual nodes in order to improve the service reliability. The presented analysis is based upon a novel use of the concept of stochastic regeneration, which is exploited to derive a system of difference-differential equations characterizing the service reliability. The theory is further utilized to optimize certain load-balancing policies for maximal service reliability; the optimization is carried out by means of an algorithm that scales linearly with the number of nodes in the system. The analytical model is validated using both Monte Carlo simulations and experimental data collected from a DCS testbed

The effect of weight, body mass index, age, sex, and race on plasma concentrations of subcutaneous sumatriptan: a pooled analysis.

Objective/backgroundFactors such as body size (weight and body mass index [BMI]), age, sex, and race might influence the clinical response to sumatriptan. We evaluated the impact of these covariates on the plasma concentration (Cp) profile of sumatriptan administered subcutaneously.MethodsWe conducted three pharmacokinetic studies of subcutaneous sumatriptan in 98 healthy adults. Sumatriptan was administered subcutaneously (236 administrations) as either DFN-11 3 mg, a novel 0.5 mL autoinjector being developed by Dr. Reddy's Laboratories; Imitrex(®) (Sumatriptan) injection 3 mg or 6 mg (6 mg/0.5 mL); or Imitrex STATdose 4 mg or 6 mg (0.5 mL). Blood was sampled for 12 hours to determine sumatriptan Cp. Maximum Cp (Cmax), area under the curve during the first 2 hours (AUC0-2), and total area under the curve (AUC0-∞) were determined using noncompartmental methods. Post hoc analyses were conducted to determine the relationship between these exposure metrics and each of body weight, BMI, age, sex, and race (categorized as white, black, or others).ResultsBoth weight and BMI correlated negatively with each exposure metric for each treatment group. Across all treatment groups, AUC0-2 for subjects with BMI less than or equal to median value was 1.03-1.12 times the value for subjects with BMI more than median value. For subjects with BMI less than or equal to median value receiving DFN-11, median AUC0-2 was slightly less than that for subjects with BMI more than median value receiving Imitrex 4 mg and larger than that for subjects with BMI more than median value receiving Imitrex 3 mg. Results were similar for the other exposure metrics and for weight. Exposure was higher in women than in men, which can be attributed in part to differences in weight. There was no relationship between exposure and age. For DFN-11, AUC0-2 and AUC0-∞ were lower in nonwhites compared with whites; the ratio of median values was 0.84 and 0.89, respectively. A similar, nonstatistically significant, trend was observed in the other products (ratio of median values ranging from 0.84 to 0.89).ConclusionWeight and BMI appear to be important covariates for sumatriptan exposure: subjects with lower values for either metric of body size have higher systemic exposure compared with subjects with higher values. Additional studies are required to determine if doses of subcutaneous sumatriptan may be adjusted based on BMI for comparable efficacy and a potentially improved tolerability profile

The Variation of Integrated Star IMFs among Galaxies

The integrated galaxial initial mass function (IGIMF) is the relevant distribution function containing the information on the distribution of stellar remnants, the number of supernovae and the chemical enrichment history of a galaxy. Since most stars form in embedded star clusters with different masses the IGIMF becomes an integral of the assumed (universal or invariant) stellar IMF over the embedded star-cluster mass function (ECMF). For a range of reasonable assumptions about the IMF and the ECMF we find the IGIMF to be steeper (containing fewer massive stars per star) than the stellar IMF, but below a few Msol it is invariant and identical to the stellar IMF for all galaxies. However, the steepening sensitively depends on the form of the ECMF in the low-mass regime. Furthermore, observations indicate a relation between the star formation rate of a galaxy and the most massive young stellar cluster in it. The assumption that this cluster mass marks the upper end of a young-cluster mass function leads to a connection of the star formation rate and the slope of the IGIMF above a few Msol. The IGIMF varies with the star formation history of a galaxy. Notably, large variations of the IGIMF are evident for dE, dIrr and LSB galaxies with a small to modest stellar mass. We find that for any galaxy the number of supernovae per star (NSNS) is suppressed relative to that expected for a Salpeter IMF. Dwarf galaxies have a smaller NSNS compared to massive galaxies. For dwarf galaxies the NSNS varies substantially depending on the galaxy assembly history and the assumptions made about the low-mass end of the ECMF. The findings presented here may be of some consequence for the cosmological evolution of the number of supernovae per low-mass star and the chemical enrichment of galaxies of different mass.Comment: 27 pages, accepted for publication by Ap

On the highly reddened members in 6 young galactic star clusters - a multiwavelength study

The spectral and reddening properties of 211 highly reddened proper motion members with $V < 15$ mag in 6 young galactic star clusters are investigated using low resolution spectroscopic, broad-band $UBVRIJHK$ and mid-IR data. We report emission features in CaII HK and HI lines for a sample of 29 stars including 11 stars reported for the first time and also provide either a new or more reliable spectral class for a sample of 24 stars. CaII triplet width measurements are used to indicate the presence of an accretion disk for a dozen stars and to hint luminosity for a couple of stars. On the basis of spectral features, near-IR excesses, dereddened color-color diagrams and mid-IR spectral indices we identify a group of 28 pre-main sequence cluster members including 5 highly probable Herbig Ae/Be and 6 classical T Tauri star. A total of 25 non-emission MS stars, amounting to $\sim$ 10 % early type MS members, appears to show Vega-like characteristics or are precursors to such a phenomenon. The various membership indicators suggest that $\sim$ 16% of the PM members are non-members. A significant fraction ($>$70%) of program stars in NGC 1976, NGC 2244, NGC 6530 and NGC 6611 show anomalous reddening with $R_{V}$ = $5.11\pm0.11$, $3.60\pm0.05$, $3.87\pm0.05$ and $3.56\pm 0.02$, respectively, indicating the presence of grain size dust larger than that typical to the diffuse medium. A small number of stars in NGC 1976, NGC 2244 and NGC 6611 also show normal behavior while the cluster NGC 6823 appears to have a normal reddening. Three highly luminous late type giants, one in NGC 2244 and two in NGC 6530, appears to be member and are in post-hydrogen-core-burning stages suggesting a prolonged duration ($\sim$ 25 Myrs) of star formation.Comment: 12 pages, 13 figures, submitted to MNRA

Efficacy and safety of DFN-11 (sumatriptan injection, 3&nbsp;mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study.

BackgroundIn a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3&nbsp;mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6&nbsp;mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2&nbsp;h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed.ResultsA total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2&nbsp;h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P  =  0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90&nbsp;min postdose (P  ≤  0.0195). DFN-11 was significantly superior to placebo for pain relief at 60&nbsp;min, 90&nbsp;min, and 2&nbsp;h postdose (P ≤ 0.0179). At 2&nbsp;h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P  =  0.0056) and phonophobia (P  =  0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%).ConclusionsThis study met its primary endpoint, pain freedom at 2&nbsp;h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3&nbsp;mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6&nbsp;mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015)

DFN-02, Sumatriptan 10 mg Nasal Spray with Permeation Enhancer, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Study Assessing Functional Disability and Subject Satisfaction with Treatment.

BackgroundThe commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10 mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2 h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.ObjectiveThe objective of this study was to assess the efficacy of acute treatment of migraine with DFN-02, including its effect on migraine-related functional disability and patient satisfaction with treatment.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-02 in adults with episodic migraine. Functional disability and subject satisfaction with treatment were prespecified endpoints, assessed in real-time by subjects, using an electronic diary.ResultsIn total, 107 subjects were randomized. DFN-02 was significantly superior to placebo for the reduction in functional disability score from predose level at 2 h after treatment (- 1.2 vs. - 0.6, p &lt; 0.001). Subjects treated with DFN-02 were also more likely to be satisfied or very satisfied than subjects treated with placebo at 2 h postdose (70.0% vs. 44.2%, p = 0.027). Using the Patient Perception of Migraine Questionnaire-Revised at 24 h postdose, DFN-02 mean scores were significantly superior to placebo for the subscales of efficacy (65.2 vs. 42.5, p = 0.016) and function (68.9 vs. 42.1, p = 0.001), and for total score (71.0 vs. 56.6, p = 0.016); global medication effectiveness (p = 0.027); and overall satisfaction (p = 0.019). Placebo was significantly better than DFN-02 on the tolerability subscale (94.8 vs. 88.5, p = 0.026). At 24 h postdose, subjects reported significantly higher satisfaction with DFN-02 compared with satisfaction reported pre-randomization regarding their usual migraine medication (p = 0.012).ConclusionDFN-02 was superior to placebo for the relief of migraine-related functional disability, and provided greater satisfaction than placebo or subjects' usual acute treatment.Trial registrationClinicalTrials.gov identifier: NCT02856802

Asceticism and the four gospels

https://place.asburyseminary.edu/ecommonsatsdissertations/2353/thumbnail.jp

Climate Change Science and Policy: Lessons from India

For more than a decade climate change has been the focus of much research and analysis. Despite the global implications of the problem the majority of research and analysis has involved researchers from industrialized countries. This paper analyzes how climate change research and analysis is performed in India, a major lesser-industrialized country. We explore the factors that play a role in shaping the capability of India to carry out, and respond to, climate change analyses. We also sketch out the links between national research and assessment capability and national policy making and how these links may have evolved and been mobilized in response to the international climate change debate. We also examine the Indian participation in, and perceptions of, the IPCC process. This allows us to reflect on the potential pitfalls for international assessment processes, and on the role that India can play in the global debate on climate change