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

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

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

The interaction of class and gender in illness narratives

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 BSA Publications Ltd.Perspectives on gender and identity that emphasize variability of performance, local context and individual agency have displaced earlier paradigms.These are now perceived to have supported gender stereotypes and language ideologies by emphasizing gender difference and homogeneity within genders. In a secondary analysis of health and illness narratives we explore the interaction of class and gender in individuals' constructions of gendered identity. High social class men perform gender in particularly varied ways and we speculate that this variable repertoire, including the use of what was once termed `women's language', is linked to a capacity to maintain social distinction and authority. Men's performance of conventional masculinity is often threatened by both the experience of illness and being interviewed about personal experience. Lower social class women in particular demonstrate an intensification of a pre-existing informal family and support group culture, marking successful members by awarding them the accolade of being `lovely'.ESR

'What is this corpus about?': Using topic modelling to explore a specialised corpus

This paper introduces topic modelling, a machine learning technique that automatically identifies 'topics' in a given corpus. The paper illustrates its use in the exploration of a corpus of academic English. It first offers the intuitive explanation of the underlying mechanism of topic modelling and describes the procedure for building a model, including the decisions involved in the model-building process. The paper then explores the model. A topic in topic models is characterised by a set of co-occurring words, and we will demonstrate that such topics bring us rich insights into the nature of a corpus. As exemplary tasks, this paper identifies the prominent topics in different parts of papers, investigates the chronological change of a journal, and reveals different types of papers in the journal. The paper further compares topic modelling to two more traditional techniques in corpus linguistics, semantic annotation and keywords analysis, and highlights the strengths of topic modelling.We believe that topic modelling is particularly useful in the initial exploration of a corpus

BN domains included into carbon nanotubes: role of interface

We present a density functional theory study on the shape and arrangement of small BN domains embedded into single-walled carbon nanotubes. We show a strong tendency for the BN hexagons formation at the simultaneous inclusion of B and N atoms within the walls of carbon nanotubes. The work emphasizes the importance of a correct description of the BN-C frontier. We suggest that BN-C interface will be formed preferentially with the participation of N-C bonds. Thus, we propose a new way of stabilizing the small BN inclusions through the formation of nitrogen terminated borders. The comparison between the obtained results and the available experimental data on formation of BN plackets within the single walled carbon nanotubes is presented. The mirror situation of inclusion of carbon plackets within single walled BN nanotubes is considered within the proposed formalism. Finally, we show that the inclusion of small BN plackets inside the CNTs strongly affects the electronic character of the initial systems, opening a band gap. The nitrogen excess in the BN plackets introduces donor states in the band gap and it might thus result in a promising way for n-doping single walled carbon nanotubes