Quality-adjusted survival as an end point in breast cancer trials

Breast cancer treatment recommendations will often require an appraisal of likely benefits in relation to likely side-effects on survival and quality of life (QoL) endpoints, and possibly also an evaluation of the size of the anticipated net clinical benefit against financial costs. Quality-adjusted survival (QAS) analysis methods provide a formal approach for deriving an estimate of net clinical benefit to facilitate this appraisal process. QAS analysis methods have been applied in trials with breast cancer patients of adjuvant therapies as well as treatments for advanced/metastatic disease. QAS analyses based solely on trial data may fail to capture plausible longer-term benefits; thus methods to explore the possible outcomes of treatment beyond the limits of trial data have been developed. These modelling approaches can help researchers gain insights and identify future research priorities, but do not replace the need for long-term evidence from randomised trials.NHMR

STM imaging of electronic waves on the surface of Bi2_2Te3_3: topologically protected surface states and hexagonal warping effects

Scanning tunneling spectroscopy studies on high-quality Bi$_2$Te$_3$ crystals exhibit perfect correspondence to ARPES data, hence enabling identification of different regimes measured in the local density of states (LDOS). Oscillations of LDOS near a step are analyzed. Within the main part of the surface band oscillations are strongly damped, supporting the hypothesis of topological protection. At higher energies, as the surface band becomes concave, oscillations appear which disperse with a particular wave-vector that may result from an unconventional hexagonal warping term.Comment: 4 pages, 4 figures. Revised manuscript with improved analysis and figure

Summer Internship Presentation, 2007

No abstract availabl

Isolation and characterisation of metallothionein from the clam Ruditapes decussatus

Aquatic Toxicology 63 (2003) 307-318Metallothioneins (MT) were obtained after purification from metal-exposed clams (Ruditapes decussatus) using gelpermeation and ion-exchange chromatography. Four cadmium /metallothioneins (CdMTs) were resolved by ionexchange chromatography and they all had similar molecular weights, high cadmium content and an absorption spectra indicative of the presence of characteristic Cd /S aggregates. The NH2-terminal sequence suggests the presence of atleast two class I clam MT isoforms. For the other two putative clam CdMTs isolated, the results of the amino acid determination were inconclusive. One was slightly contaminated and the other one had a blocked NH2-terminal. These clam metalothioneins contain glycine, which seems to be a common feature of molluscan MT family and exhibited more similarity to oysters than to mussels. Further investigation on the inducibility of these isoforms will be necessary if clams are to be used as biomarkers of metal exposure

Linking the evidence: intermediate outcomes in medical test assessments

Objectives To review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes. Methods Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the websites of International Network of Agencies for Health Technology Assessment (INAHTA) members. Results 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In 71 HTAs (48%) only diagnostic accuracy was reported, while in 17 (11%) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in 61 HTAs (41%). Of these, 47 identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in about 60% of HTAs. Conclusions Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies

Localization of osteocalcin (BGP) during fish (Sparus aurata) development by in situ hybridization and immunohistochemistry: comparison between gene expression/protein distribution and skeletal mineralization

Osteocalcin (Bone Gla protein, BGP) is a small noncollagenous protein which is synthesized by osteoblasts and odontoblasts and is found exlusively in mineralized bony tissues. Although isolated for the first time in 1978, only recently has a function for this protein been suggested, specifically in controlling hydroxyapatite crystal growth. Appearance of osteocalcin could be linked to the presence of an hydroxyapatite-containing bony skeleton, since the protein was never found in cartilaginous fishes. Furthermore, within its primary sequence the amino acid residues known to be essential for its function are present in fish as well as in mammals, suggesting that function has been conserved over 400 million years of evolution. Taken totgether, these findings prompted us to study in detail the localization of osteocalcin gene expression in fish

Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: A meta-analysis

Background: Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. Methods: In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Results: Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest (r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2 = 0.66; platinum/paclitaxel, r2 = 0.44; triplet combinations, r2 = 0.22; biologicals, r2 = 0.30. The median PPS increased over time for the experimental (Ptrend = 0.03) and control arms (Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS (r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger (r2 = 0.64) than where the median PPS was longer (r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies