The Chemical Evolution of the Milky Way

The field of chemical evolution modeling of the Galaxy is experiencing in the last years a phase of high activity and important achievements. There are, however, several open questions which still need to be answered. In this review I summarize what have been the most important achievements and what are some of the most urgent questions to be answered.Comment: 10 pages including 3 figs, to appear in "The Chemical Evolution of the Milky Way. Stars vs Clusters", Proceedings of the Sept.1999 Vulcano Workshop, F.Giovannelli and F.Matteucci eds (Kluwer, Dordrecht) in pres

The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT

A phase i pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours

Background: The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. Methods: Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m -2 with 75 mg m -2 docetaxel, then from 30 to 35 mg m -2 with 100 mg m -2 docetaxel. Recommended phase II dose cohorts were expanded. Results: Fifty-eight patients were treated. Recommended phase II doses were 35 mg m -2 ombrabulin with 75 mg m -2 docetaxel (35/75 mg m -2; 13 patients) and 30 mg m -2 ombrabulin with 100 mg m -2 docetaxel (30/100 mg m -2; 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m -2 docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m -2 ombrabulin), eight lasting >3 months. Conclusions: Sequential administration of ombrabulin with 75 or 100 mg m -2 docetaxel every 3 weeks is feasible

Subduction controls the distribution and fragmentation of Earth’s tectonic plates

International audienceThe theory of plate tectonics describes how the surface of the Earth is split into an organized jigsaw of seven large plates 1 of similar sizes and a population of smaller plates, whose areas follow a fractal distribution 2,3. The reconstruction of global tectonics during the past 200 My 4 suggests that this layout is probably a long-term feature of our planet, but the forces governing it are unknown. Previous studies 3,5,6 , primarily based on statistical properties of plate distributions, were unable to resolve how the size of plates is determined by lithosphere properties and/or underlying mantle convection. Here, we demonstrate that the plate layout of the Earth is produced by a dynamic feedback between mantle convection and the strength of the lithosphere. Using 3D spherical models of mantle convection with plate-like behaviour that match the plate size-frequency distribution observed for Earth, we show that subduction geometry drives the tectonic fragmentation that generates plates. The spacing between slabs controls the layout of large plates, and the stresses caused by the bending of trenches, break plates into smaller fragments. Our results explain why the fast evolution in small back-arc plates 7,8 reflects the dramatic changes in plate motions during times of major reorganizations. Our study opens the way to use convection simulations with plate-like behaviour to unravel how global tectonics and mantle convection are dynamically connected

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Comparative in situ analyses of cell wall matrix polysaccharide dynamics in developing rice and wheat grain

Cell wall polysaccharides of wheat and rice endosperm are an important source of dietary fibre. Monoclonal antibodies specific to cell wall polysaccharides were used to determine polysaccharide dynamics during the development of both wheat and rice grain. Wheat and rice grain present near synchronous developmental processes and significantly different endosperm cell wall compositions, allowing the localisation of these polysaccharides to be related to developmental changes. Arabinoxylan (AX) and mixed-linkage glucan (MLG) have analogous cellular locations in both species, with deposition of AX and MLG coinciding with the start of grain filling. A glucuronoxylan (GUX) epitope was detected in rice, but not wheat endosperm cell walls. Callose has been reported to be associated with the formation of cell wall outgrowths during endosperm cellularisation and xyloglucan is here shown to be a component of these anticlinal extensions, occurring transiently in both species. Pectic homogalacturonan (HG) was abundant in cell walls of maternal tissues of wheat and rice grain, but only detected in endosperm cell walls of rice in an unesterified HG form. A rhamnogalacturonan-I (RG-I) backbone epitope was observed to be temporally regulated in both species, detected in endosperm cell walls from 12 DAA in rice and 20 DAA in wheat grain. Detection of the LM5 galactan epitope showed a clear distinction between wheat and rice, being detected at the earliest stages of development in rice endosperm cell walls, but not detected in wheat endosperm cell walls, only in maternal tissues. In contrast, the LM6 arabinan epitope was detected in both species around 8 DAA and was transient in wheat grain, but persisted in rice until maturity

Gender differences in disability after sickness absence with musculoskeletal disorders: five-year prospective study of 37,942 women and 26,307 men

<p>Abstract</p> <p>Background</p> <p>Gender differences in the prevalence and occupational consequences of musculoskeletal disorders (MSDs) are consistently found in epidemiological studies. The study investigated whether gender differences also exist with respect to chronicity, measured as the rate of transition from sickness absence into permanent disability pension (DP).</p> <p>Methods</p> <p>Prospective national cohort study in Norway including all cases with a spell of sickness absence > eight weeks during 1997 certified with a MSD, 37,942 women and 26,307 men. The cohort was followed-up for five years with chronicity measured as granting of DP as the endpoint. The effect of gender was estimated in the full sample adjusting for sociodemographic factors and diagnostic distribution. Gender specific analyses were performed with the same explanatory variables. Finally, the gender difference was estimated for nine diagnostic subgroups.</p> <p>Results</p> <p>The crude rate of DP was 22% for women and 18% for men. After adjusting for all sociodemographic variables, a slightly higher female risk of DP remained. However, additional adjustment for diagnostic distribution removed the gender difference completely. Having children and working full time decreased the DP risk for both genders, whereas low socioeconomic status increased the risk similarly. There was a different age effect as more women obtained a DP below the age of 50. Increased female risk of chronicity remained for myalgia/fibromyalgia, back disorders and "other/unspecified" after relevant adjustments, whereas men with neck disorders were at higher risk of chronicity.</p> <p>Conclusions</p> <p>Women with MSDs had a moderately increased risk of chronicity compared to men, when including MSDs with a traumatic background. Possible explanations are lower income, a higher proportion belonging to diagnostic subgroups with poor prognosis, and a younger age of chronicity among women. When all sociodemographic and diagnostic variables were adjusted for, no gender difference remained, except for some diagnostic subgroups.</p

The Resolved Stellar Populations in the LEGUS Galaxies1

This is the final version. Available from American Astronomical Society via the DOI in this recordThe Legacy ExtraGalactic UV Survey (LEGUS) is a multiwavelength Cycle 21 Treasury program on the Hubble Space Telescope. It studied 50 nearby star-forming galaxies in 5 bands from the near-UV to the I-band, combining new Wide Field Camera 3 observations with archival Advanced Camera for Surveys data. LEGUS was designed to investigate how star formation occurs and develops on both small and large scales, and how it relates to the galactic environments. In this paper we present the photometric catalogs for all the apparently single stars identified in the 50 LEGUS galaxies. Photometric catalogs and mosaicked images for all filters are available for download. We present optical and near-UV color-magnitude diagrams for all the galaxies. For each galaxy we derived the distance from the tip of the red giant branch. We then used the NUV color-magnitude diagrams to identify stars more massive than 14 Mo, and compared their number with the number of massive stars expected from the GALEX FUV luminosity. Our analysis shows that the fraction of massive stars forming in star clusters and stellar associations is about constant with the star formation rate. This lack of a relation suggests that the timescale for evaporation of unbound structures is comparable or longer than 10 Myr. At low star formation rates this translates to an excess of mass in clustered environments as compared to model predictions of cluster evolution, suggesting that a significant fraction of stars form in unbound systems.A.A. acknowledges partial support from the Swedish Royal Academy. G.A. acknowledges support from the Science and Technology Facilities Council (ST/L00075X/1 and ST/ M503472/1). C.D. acknowledges funding from the FP7 ERC starting grant LOCALSTAR (no. 280104). M.F. acknowledges support by the Science and Technology Facilities Council (grant number ST/L00075X/1). D.A.G. kindly acknowledges financial support by the German Research Foundation (DFG) through program GO1659/3-2. These observations are associated with program # 13364. Support for program # 13364 was provided by NASA through a grant from the Space Telescope Science Institute. This work is based on observations obtained with the NASA/ESA Hubble Space Telescope, at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555

Diagnostic techniques for inflammatory eye disease: past, present and future: a review

Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials

Interferon-Inducible CXC Chemokines Directly Contribute to Host Defense against Inhalational Anthrax in a Murine Model of Infection

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms