Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m−2 twice daily, days 1–14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m−2, (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m−2 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17–59%) with capecitabine (including three complete responses) and 26% (95% CI 9–51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand–foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a ⩾10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy

Scalar-mediated ttˉt\bar t forward-backward asymmetry

A large forward-backward asymmetry in $t\bar t$ production, for large invariant mass of the $t\bar t$ system, has been recently observed by the CDF collaboration. Among the scalar mediated mechanisms that can explain such a large asymmetry, only the t-channel exchange of a color-singlet weak-doublet scalar is consistent with both differential and integrated $t\bar t$ cross section measurements. Constraints from flavor changing processes dictate a very specific structure for the Yukawa couplings of such a new scalar. No sizable deviation in the differential or integrated $t\bar t$ production cross section is expected at the LHC.Comment: 22 pages, 1 figure and 2 tables. v2: Corrected Eqs.(50,51,74), adapted Fig.1, Tab.1 and relevant discussions. Extended discussion of top decay and single to

On theories of enhanced CP violation in B_s,d meson mixing

The DO collaboration has measured a deviation from the standard model (SM) prediction in the like sign dimuon asymmetry in semileptonic b decay with a significance of 3.2 sigma. We discuss how minimal flavour violating (MFV) models with multiple scalar representations can lead to this deviation through tree level exchanges of new MFV scalars. We review how the two scalar doublet model can accommodate this result and discuss some of its phenomenology. Limits on electric dipole moments suggest that in this model the coupling of the charged scalar to the right handed u-type quarks is suppressed while its coupling to the d-type right handed quarks must be enhanced. We construct an extension of the MFV two scalar doublet model where this occurs naturally.Comment: 10 pages, 7 figures, v3 final JHEP versio

CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments

We study electroweak baryogenesis and electric dipole moments in the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM. Significant qualitative and quantitative differences from MSSM baryogenesis arise due to the presence of new CP-violating phases and to the relaxation of constraints on the supersymmetric spectrum (in particular, both stops can be light). We find: (1) spontaneous baryogenesis, driven by a change in the phase of the Higgs vevs across the bubble wall, becomes possible; (2) the top and stop CP-violating sources can become effective; (3) baryogenesis is viable in larger parts of parameter space, alleviating the well-known fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole moments should be measured if experimental sensitivities are improved by about one order of magnitude.Comment: 33 pages, 6 figure

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

Suppressing Electroweak Precision Observables in 5D Warped Models

We elaborate on a recently proposed mechanism to suppress large contributions to the electroweak precision observables in five dimensional (5D) warped models, without the need for an extended 5D gauge sector. The main ingredient is a modification of the AdS metric in the vicinity of the infrared (IR) brane corresponding to a strong deviation from conformality in the IR of the 4D holographic dual. We compute the general low energy effective theory of the 5D warped Standard Model, emphasizing additional IR contributions to the wave function renormalization of the light Higgs mode. We also derive expressions for the S and T parameters as a function of a generic 5D metric and zero-mode wave functions. We give an approximate formula for the mass of the radion that works even for strong deviation from the AdS background. We proceed to work out the details of an explicit model and derive bounds for the first KK masses of the various bulk fields. The radion is the lightest new particle although its mass is already at about 1/3 of the mass of the lightest resonances, the KK states of the gauge bosons. We examine carefully various issues that can arise for extreme choices of parameters such as the possible reintroduction of the hierarchy problem, the onset of nonperturbative physics due to strong IR curvature or the creation of new hierarchies near the Planck scale. We conclude that a KK scale of 1 TeV is compatible with all these constraints.Comment: 44 pages, 11 figures, references adde

A decade of inequality in maternity care: antenatal care, professional attendance at delivery, and caesarean section in Bangladesh (1991–2004)

<p>Abstract</p> <p>Background</p> <p>Bangladesh is committed to the fifth Millennium Development Goal (MDG-5) target of reducing its maternal mortality ratio by three-quarters between 1990 and 2015. Since the early 1990s, Bangladesh has followed a strategy of improving access to facilities equipped and staffed to provide emergency obstetric care (EmOC).</p> <p>Methods</p> <p>We used data from four Demographic and Health Surveys conducted between 1993 and 2004 to examine trends in the proportions of live births preceded by antenatal consultation, attended by a health professional, and delivered by caesarean section, according to key socio-demographic characteristics.</p> <p>Results</p> <p>Utilization of antenatal care increased substantially, from 24% in 1991 to 60% in 2004. Despite a relatively greater increase in rural than urban areas, utilization remained much lower among the poorest rural women without formal education (18%) compared with the richest urban women with secondary or higher education (99%). Professional attendance at delivery increased by 50% (from 9% to 14%, more rapidly in rural than urban areas), and caesarean sections trebled (from 2% to 6%), but these indicators remained low even by developing country standards. Within these trends there were huge inequalities; 86% of live births among the richest urban women with secondary or higher education were attended by a health professional, and 35% were delivered by caesarean section, compared with 2% and 0.1% respectively of live births among the poorest rural women without formal education. The trend in professional attendance was entirely confounded by socioeconomic and demographic changes, but education of the woman and her husband remained important determinants of utilization of obstetric services.</p> <p>Conclusion</p> <p>Despite commendable progress in improving uptake of antenatal care, and in equipping health facilities to provide emergency obstetric care, the very low utilization of these facilities, especially by poor women, is a major impediment to meeting MDG-5 in Bangladesh.</p

Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease

Background: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. Methods: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM+CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. Results: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r=0.57, p<0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD+DM (p=0.030). Patients suffering from CVD+DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p=0.006) and time needed to reach arterial maximum dilation (p=0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD+DM compared to the other two groups (p≤0.02), whilst sEsel was raised in CVD+DM compared to DM alone (p=0.044). Conclusions: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression

Planet formation in Binaries

Spurred by the discovery of numerous exoplanets in multiple systems, binaries have become in recent years one of the main topics in planet formation research. Numerous studies have investigated to what extent the presence of a stellar companion can affect the planet formation process. Such studies have implications that can reach beyond the sole context of binaries, as they allow to test certain aspects of the planet formation scenario by submitting them to extreme environments. We review here the current understanding on this complex problem. We show in particular how each of the different stages of the planet-formation process is affected differently by binary perturbations. We focus especially on the intermediate stage of kilometre-sized planetesimal accretion, which has proven to be the most sensitive to binarity and for which the presence of some exoplanets observed in tight binaries is difficult to explain by in-situ formation following the "standard" planet-formation scenario. Some tentative solutions to this apparent paradox are presented. The last part of our review presents a thorough description of the problem of planet habitability, for which the binary environment creates a complex situation because of the presence of two irradation sources of varying distance.Comment: Review chapter to appear in "Planetary Exploration and Science: Recent Advances and Applications", eds. S. Jin, N. Haghighipour, W.-H. Ip, Springer (v2, numerous typos corrected