Low complexity method for large-scale self-consistent ab initio electronic-structure calculations without localization

A novel low complexity method to perform self-consistent electronic-structure calculations using the Kohn-Sham formalism of density functional theory is presented. Localization constraints are neither imposed nor required thereby allowing direct comparison with conventional cubically scaling algorithms. The method has, to date, the lowest complexity of any algorithm for an exact calculation. A simple one-dimensional model system is used to thoroughly test the numerical stability of the algorithm and results for a real physical system are also given

Cost-utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

BACKGROUND: Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost-utility (cu) of this therapy could help to determine its role in clinical practice. METHODS: Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. RESULTS: Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and$7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and$23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained. CONCLUSIONS: Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds

A framework for P2P application development

Although Peer-to-Peer (P2P) computing has become increasingly popular over recent years, there still exist only a very small number of application domains that have exploited it on a large scale. This can be attributed to a number of reasons including the rapid evolution of P2P technologies, coupled with their often-complex nature. This paper describes an implemented abstraction framework that seeks to aid developers in building P2P applications. A selection of example P2P applications that have been developed using this framework are also presented

Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies

Anthracycline-trastuzumab-containing regimens demonstrate significant clinical activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, the utility of this strategy is limited by unacceptably high rates of significant cardiotoxicity, particularly with concurrent administration. Anthracycline-induced cardiotoxicity is thought to be mediated primarily through increased myocardial oxidative stress, modified partly by the activity of neuregulins. Trastuzumab-induced cardiotoxicity is thought to be mediated by the ErbB/neuregulin system, with exposure to trastuzumab partly blocking the protective effect of neuregulins on the myocardium. As a result, trastuzumab increases the risk of anthracycline-induced cardiotoxicity. Several strategies have been adopted in attempts to minimize cardiotoxicity, including patient selection on the basis of preexisting cardiac risk, monitoring of cardiac function during treatment, and early management of cardiac dysfunction. The use of less cardiotoxic anthracyclines may be one strategy to lessen the risk of cardiotoxicity. Liposomal doxorubicin products offer similar efficacy compared with conventional doxorubicin, with significantly less cardiotoxicity, and have been successfully used in combination with trastuzumab in the metastatic and neo-adjuvant setting. Clinical trials are currently underway to assess the safety of pegylated liposomal doxorubicin during concurrent administration with trastuzumab compared with standard sequential treatment using conventional doxorubicin in the adjuvant settin

Wait times for breast cancer care

Measurement of care time intervals is complex, being influenced by many factors. The definition of the care interval monitored can also bias the detection of changes in waits. The implications of using different care interval definitions to report wait times and identify delays in care provision were examined using a retrospective chart review of 637 women with surgically treated breast cancer who were referred to a cancer centre between September 1999 and 2000 or September 2003 and 2004. Overall waits between detection and adjuvant treatment increased by 12 days over the two periods, but their exact location and cause(s) could not be determined at such a low-resolution interval. At higher resolutions of care intervals, reporting the comprehensive sequence of care events, the prolongation was mainly associated with delayed access to surgery (4 days) and delivery of adjuvant chemotherapy (4 days). The latter went unnoticed when waits were reported at intermediate (referral to adjuvant treatment) and low (detection to adjuvant treatment) resolutions. Disease stage and type of first adjuvant treatment consistently and significantly influenced the length of waits. Comprehensive monitoring of the entire care path is essential to effectively prioritize interventions, assess their outcomes and optimise access to cancer care