Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression

One-loop determination of mass dependent O(a)O(a) improvement coefficients for the heavy-light vector and axial-vector currents with relativistic heavy and domain-wall light quarks

We present the one-loop results of the mass dependent $O(a)$ improvement coefficients for the heavy-light vector and axial-vector currents consisting of the relativistic heavy and the domain-wall light quarks. The calculations are performed with the plaquette, Iwasaki and DBW2 gauge actions. The heavy quark mass and domain-wall height dependence is investigated. We point out that the exact chiral symmetry held by the lattice light quark action leads to an exact relation between the improvement coefficients for the vector and axial-vector currents without regard to the lattice heavy quark action.Comment: 3 pages, 1 figure, talk presented at Lattice2004(improved), Fermilab, June 21-26, 200

Learning Best Response Strategies for Agents in Ad Exchanges

Ad exchanges are widely used in platforms for online display advertising. Autonomous agents operating in these exchanges must learn policies for interacting profitably with a diverse, continually changing, but unknown market. We consider this problem from the perspective of a publisher, strategically interacting with an advertiser through a posted price mechanism. The learning problem for this agent is made difficult by the fact that information is censored, i.e., the publisher knows if an impression is sold but no other quantitative information. We address this problem using the Harsanyi-Bellman Ad Hoc Coordination (HBA) algorithm, which conceptualises this interaction in terms of a Stochastic Bayesian Game and arrives at optimal actions by best responding with respect to probabilistic beliefs maintained over a candidate set of opponent behaviour profiles. We adapt and apply HBA to the censored information setting of ad exchanges. Also, addressing the case of stochastic opponents, we devise a strategy based on a Kaplan-Meier estimator for opponent modelling. We evaluate the proposed method using simulations wherein we show that HBA-KM achieves substantially better competitive ratio and lower variance of return than baselines, including a Q-learning agent and a UCB-based online learning agent, and comparable to the offline optimal algorithm

Exploring Hyperons and Hypernuclei with Lattice QCD

In this work we outline a program for lattice QCD that would provide a first step toward understanding the strong and weak interactions of strange baryons. The study of hypernuclear physics has provided a significant amount of information regarding the structure and weak decays of light nuclei containing one or two Lambda's, and Sigma's. From a theoretical standpoint, little is known about the hyperon-nucleon interaction, which is required input for systematic calculations of hypernuclear structure. Furthermore, the long-standing discrepancies in the P-wave amplitudes for nonleptonic hyperon decays remain to be understood, and their resolution is central to a better understanding of the weak decays of hypernuclei. We present a framework that utilizes Luscher's finite-volume techniques in lattice QCD to extract the scattering length and effective range for Lambda-N scattering in both QCD and partially-quenched QCD. The effective theory describing the nonleptonic decays of hyperons using isospin symmetry alone, appropriate for lattice calculations, is constructed.Comment: 24 pages, 7 figure

The Elephants in the Room: Sex, HIV, and LGBT Populations in MENA. Intersectionality in Lebanon Comment on “Improving the Quality and Quantity of HIV Data in the Middle East and North Africa: Key Challenges and Ways Forward”

In response to this insightful editorial, we wish to provide commentary that seeks to highlight recent successes and illuminate the often unspoken hurdles at the intersections of culture, politics, and taboo. We focus on sexual transmission and draw examples from Lebanon, where the pursuit of data in quality and quantity is teaching us lessons about the way forward and where we are experiencing many of the challenges referenced in the editorial such as discrepancies between national statistics and rates derived via research as well as the impact of protracted political conflict and displacement. Two important points were raised in the editorial about HIV in Middle East and North Africa (MENA) that we would like to expand further: (1) The epidemic is largely driven by drug-related and sexual behavior among key populations; and (2) Several key populations continue to be criminalized and excluded from surveillance programs

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

Discovery potential of top-partners in a realistic composite Higgs model with early LHC data

Composite Higgs models provide a natural, non-supersymmetric solution to the hierarchy problem. In these models, one or more sets of heavy top-partners are typically introduced. Some of these new quarks can be relatively light, with a mass of a few hundred GeV, and could be observed with the early LHC collision data expected to be collected during 2010. We analyse in detail the collider signatures that these new quarks can produce. We show that final states with two (same-sign) or three leptons are the most promising discovery channels. They can yield a 5 sigma excess over the Standard Model expectation already with the 2010 LHC collision data. Exotic quarks of charge 5/3 are a distinctive feature of this model. We present a new method to reconstruct their masses from their leptonic decay without relying on jets in the final state.Comment: 28 pages 11 Figures 7 Tables, minor changes, added references, matches published versio

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel