Reduction of Subtask Dispersion in Fork-Join Systems

Abstract. Fork-join and split-merge queueing systems are well-known abstractions of parallel systems in which each incoming task splits into subtasks that are processed by a set of parallel servers. A task exits the system when all of its subtasks have completed service. Two key metrics of interest in such systems are task response time and subtask dispersion. This paper presents a technique applicable to a class of fork-join systems with heterogeneous exponentially distributed service times that is able to reduce subtask dispersion with only a marginal increase in task response time. Achieving this is challenging since the unsynchronised operation of fork-join systems naturally militates against low subtask dispersion. Our approach builds on our earlier research examining subtask dispersion and response time in split-merge systems, and involves the frequent application and updating of delays to the subtasks at the head of the parallel service queues. Numerical results show the ability to reduce dispersion in fork-join systems to levels comparable with or below that observed in all varieties of split-merge systems while retaining the response time and throughput benefits of a fork-join system

Long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure : primary results of the ENABLE Trials

Objectives: The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background: Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods: In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial was clinical status at 9 months (assessed by the hierarchical clinical composite); the primary outcome across the 2 trials was death from any cause or hospitalization for heart failure. Results: Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions: Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention