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

Results on improved KS dynamical configurations: spectrum, decay constants, etc

The MILC Collaboration has been producing ensembles of lattice configurations with three dynamical flavors for the past few years. There are now results for three lattice spacings for a variety of light and strange quark masses, ranging down to $m_l=0.1 m_s$, where $m_s$ is the dynamical strange quark mass and $m_l$ is the common mass of the $u$ and $d$ quarks. Recently, the Fermilab, HPQCD, MILC and UKQCD collaborations have presented a summary of results obtained using these lattices. Compared with quenched results, these new calculations show great improvement in agreement with experiment. This talk addresses the technical improvements that make these calculations possible and provides additional details of calculations not presented in the initial summary. We demonstrate that a wide range of hadronic observables can now be calculated to 2--3% accuracy.Comment: 10 pages, 17 figures (16 in color), Lattice2003(plenary), Plenary talk presented at Lattice 2003, Tsukuba, Japan, July 15-19. Also presented at Lattice Hadron Physics workshop, Cairns, Australia, July 22-30, 200

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

Lattice Gauge Theory -- Present Status

Lattice gauge theory is our primary tool for the study of non-perturbative phenomena in hadronic physics. In addition to giving quantitative information on confinement, the approach is yielding first principles calculations of hadronic spectra and matrix elements. After years of confusion, there has been significant recent progress in understanding issues of chiral symmetry on the lattice. (Talk presented at HADRON 93, Como, Italy, June 1993.)Comment: 11 pages, BNL-4946

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

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections

Ca(2+)-independent F-actin assembly and disassembly during Fc receptor-mediated phagocytosis in mouse macrophages

Phagocytosis of IgG-coated particles by macrophages is presumed to involve the actin-based cytoskeleton since F-actin accumulates beneath forming phagosomes, and particle engulfment is blocked by cytochalasins, drugs that inhibit actin filament assembly. However, it is unknown whether Fc receptor ligation affects the rate or extent of F-actin assembly during phagocytosis of IgG-coated particles. To examine this question we have used a quantitative spectrofluorometric method to examine F-actin dynamics during a synchronous wave of phagocytosis of IgG-coated red blood cells by inflammatory mouse macrophages. We observed a biphasic rise in macrophage F-actin content during particle engulfment, with maxima at 1 and 5 min after the initiation of phagocytosis. F-actin declined to resting levels by 30 min, by which time particle engulfment was completed. These quantitative increases in macrophage F-actin were reflected in localized changes in F-actin distribution. Previous work showed that the number of IgG-coated particles engulfed by macrophages is unaffected by buffering extracellular calcium or by clamping cytosolic free calcium concentration ([Ca2+]i) to very low levels (Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. J. Cell Biol. 106: 657-666). To determine whether clamping [Ca2+]i in macrophages affects the rate of particle engulfment, or the assembly or disassembly of F-actin during phagocytosis, we examined these parameters in macrophages whose [Ca2+]i had been clamped to approximately less than 3 nM with fura 2/AM and acetoxymethyl ester of EGTA. We found that the initial rate of phagocytosis, and the quantities of F-actin assembled and disassembled were similar in Ca(2+)-replete and Ca(2+)-depleted macrophages. We conclude that Fc receptor-mediated phagocytosis in mouse macrophages is accompanied by an ordered sequence of assembly and disassembly of F-actin that is insensitive to [Ca2+]i

Perturbative determination of mass dependent renormalization and improvement coefficients for the heavy-light vector and axial-vector currents with relativistic heavy and domain-wall light quarks

We determine the mass dependent renormalization as well as improvement coefficients for the heavy-light vector and axial-vector currents consisting of the relativistic heavy and the domain-wall light quarks through the standard matching procedure. The calculation is carried out perturbatively at the one loop level to remove the systematic error of O(\alpha_s (am_Q)^n a\p) as well as $O(\alpha_s (am_Q)^n)$ ($n\ge$0), where \p is a typical momentum scale in the heavy-light system. We point out that renormalization and improvement coefficients of the heavy-light vector current agree with those of the axial-vector current, thanks to the exact chiral symmetry for the light quark. The results obtained with three different gauge actions, plaquette, Iwasaki and DBW2, are presented as a function of heavy quark mass and domain-wall height.Comment: 33 pages, 6 figure

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