A model-based approach for multiple QoS in scheduling: from models to implementation

Meeting multiple Quality of Service (QoS) requirements is an important factor in the success of complex software systems. This paper presents an automated, model-based scheduler synthesis approach for scheduling application software tasks to meet multiple QoS requirements. As a first step, it shows how designers can meet deadlock-freedom and timeliness requirements, in a manner that (i) does not over-provision resources, (ii) does not require architectural changes to the system, and that (iii) leaves enough degrees of freedom to pursue further properties. A major benefit of our synthesis methodology is that it increases traceability, by linking each scheduling constraint with a specific pair of QoS property and underlying platform execution model, so as to facilitate the validation of the scheduling constraints and the understanding of the overall system behaviour, required to meet further QoS properties. The paper shows how the methodology is applied in practice and also presents a prototype implementation infrastructure for executing an application on top of common operating systems, without requiring modifications of the latter

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Background Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs). Findings We received data on 18 766 women (18 206 [97%] in trials of 2–5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87–1·01; 2p=0·08), distant recurrence (0·92, 0·85–0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83–0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73–0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78–0·94; 2p=0·002), distant recurrence (0·82, 0·74–0·92; 2p=0·0003), bone recurrence (0·72, 0·60–0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73–0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75–0·97; 2p=0·02). Interpretation Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began. Funding Cancer Research UK, Medical Research Council

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Static scheduling of pipelined periodic tasks in distributed real-time systems

Many distributed real time applications involve periodic activities with end to end timing constraints that are larger than the periods. That is, a new instance of a periodic activity will come into existence before the previous instance has been completed. Also, such activities typically involve communicating modules in a distributed system where some modules may be replicated for resilience. For such activities, pipelined execution allows us to meet the various resource and timing constraints imposed on them. We discuss an approach to dealing with the pipelined execution of a set of periodic activities that have the above characteristics. It can be called a meta algorithm since it works in conjunction with another scheduling algorithm-one that creases the actual schedules. The idea is to exploit the existence of many such scheduling algorithms, which, however typically work with activities whose deadlines are equal to or less than their periods. Our meta algorithm invokes such a scheduling algorithm, perhaps multiple times, to generate a pipelined execution for the tasks. The effectiveness of the approach is shown via simulation studies

A Framework for Composing Real-Time Schedulers

In this paper, we present a framework for integrating real-time components in the same system, where each component has its own scheduling algorithm. There are two main reasons for this research: to allow maximum exibility in the design of systems with different real-time activities and to reuse already existing applications without changing their scheduling policy. After defining the concept of component in our context, we present our methodology that is based on a two-level hierarchical scheduling paradigm. At the global level, a scheduler selects which component must be executed at each instant; the selected component then chooses which task has to be scheduled depending on its own scheduling strategy