Computable bounds in fork-join queueing systems

In a Fork-Join (FJ) queueing system an upstream fork station splits incoming jobs into N tasks to be further processed by N parallel servers, each with its own queue; the response time of one job is determined, at a downstream join station, by the maximum of the corresponding tasks' response times. This queueing system is useful to the modelling of multi-service systems subject to synchronization constraints, such as MapReduce clusters or multipath routing. Despite their apparent simplicity, FJ systems are hard to analyze. This paper provides the first computable stochastic bounds on the waiting and response time distributions in FJ systems. We consider four practical scenarios by combining 1a) renewal and 1b) non-renewal arrivals, and 2a) non-blocking and 2b) blocking servers. In the case of non blocking servers we prove that delays scale as O(logN), a law which is known for first moments under renewal input only. In the case of blocking servers, we prove that the same factor of log N dictates the stability region of the system. Simulation results indicate that our bounds are tight, especially at high utilizations, in all four scenarios. A remarkable insight gained from our results is that, at moderate to high utilizations, multipath routing 'makes sense' from a queueing perspective for two paths only, i.e., response times drop the most when N = 2; the technical explanation is that the resequencing (delay) price starts to quickly dominate the tempting gain due to multipath transmissions

Neutron personal dosimetry using polyallyl diglycol carbonate (PADC): Current status, best practices and proposed research

The objective of this paper is to provide an overview of the current status in neutron personal dosimetry based on poly allyl diglycol carbonate (PADC), also commonly known by the commercial name CR-39, to summarize the best practices in the field, and to point future research directions. An overview of the fundamentals of the technique is given, including a discussion on the PADC material, main parameters and characteristics, practical considerations, dosimetry approaches, and relevant standards. This work also summarizes the best practices adopted by individual monitoring services (IMSs) and discusses the research needed to improve the performance of this type of neutron dosimetry technique, as well as the challenges that make progress difficult. This work is based on the knowledge and experience of several laboratories and investigators and is part of the activities of the European Radiation Dosimetry Group (EURADOS) Working Group 2 – Harmonization of Individual Monitoring in Europe (WG2)

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

A total of 53 women with chemotherapy-naý¨ve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mgm 2 (days 1, 8, and 15) and gemcitabine 1000 mgm 2 (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour 42 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, 7 decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane–gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated

Impact of foot-and-mouth disease on mastitis and culling on a large-scale dairy farm in Kenya

Foot and mouth disease (FMD) is a highly transmissible viral infection of cloven hooved animals associated with severe economic losses when introduced into FMD-free countries. Information on the impact of the disease in FMDV-endemic countries is poorly characterised yet essential for the prioritisation of scarce resources for disease control programmes. A FMD (virus serotype SAT2) outbreak on a large-scale dairy farm in Nakuru County, Kenya provided an opportunity to evaluate the impact of FMD on clinical mastitis and culling rate. A cohort approach followed animals over a 12-month period after the commencement of the outbreak. For culling, all animals were included; for mastitis, those over 18 months of age. FMD was recorded in 400/644 cattle over a 29-day period. During the follow-up period 76 animals were culled or died whilst in the over 18 month old cohort 63 developed clinical mastitis. Hazard ratios (HR) were generated using Cox regression accounting for non-proportional hazards by inclusion of time-varying effects. Univariable analysis showed FMD cases were culled sooner but there was no effect on clinical mastitis. After adjusting for possible confounders and inclusion of time-varying effects there was weak evidence to support an effect of FMD on culling (HR = 1.7, 95% confidence intervals [CI] 0.88-3.1, P = 0.12). For mastitis, there was stronger evidence of an increased rate in the first month after the onset of the outbreak (HR = 2.9, 95%CI 0.97-8.9, P = 0.057)

Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)

Bovine TB is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5%, while the accuracy of the test employed to detect infected cattle explained less than 3% of the variance in the number of infected cattle

Balancing Detection and Eradication for Control of Epidemics: Sudden Oak Death in Mixed-Species Stands

Culling of infected individuals is a widely used measure for the control of several plant and animal pathogens but culling first requires detection of often cryptically-infected hosts. In this paper, we address the problem of how to allocate resources between detection and culling when the budget for disease management is limited. The results are generic but we motivate the problem for the control of a botanical epidemic in a natural ecosystem: sudden oak death in mixed evergreen forests in coastal California, in which species composition is generally dominated by a spreader species (bay laurel) and a second host species (coast live oak) that is an epidemiological dead-end in that it does not transmit infection but which is frequently a target for preservation. Using a combination of an epidemiological model for two host species with a common pathogen together with optimal control theory we address the problem of how to balance the allocation of resources for detection and epidemic control in order to preserve both host species in the ecosystem. Contrary to simple expectations our results show that an intermediate level of detection is optimal. Low levels of detection, characteristic of low effort expended on searching and detection of diseased trees, and high detection levels, exemplified by the deployment of large amounts of resources to identify diseased trees, fail to bring the epidemic under control. Importantly, we show that a slight change in the balance between the resources allocated to detection and those allocated to control may lead to drastic inefficiencies in control strategies. The results hold when quarantine is introduced to reduce the ingress of infected material into the region of interest

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals