The Super Star Cluster NGC 1569-A Resolved on Sub-Parsec Scales with Hubble Space Telescope Spectroscopy

We present 3000--10000 Ang HST/STIS long-slit spectroscopy of the bright super star cluster A (SSC-A) in the dwarf starburst galaxy NGC 1569. The 0.05" HST angular resolution allows, for the first time, to probe for spatial variations in the stellar population of a ~ 10^6 M_sun SSC. Integrated ground-based spectra of SSC-A have previously revealed young Wolf-Rayet (WR) signatures that coexist with features from supposedly older, red supergiant (RSG), populations. We find that the WR emission complexes come solely from the subcluster A2, identified in previous HST imaging, and are absent from the main cluster A1, thus resolving the question of whether the WR and RSG features arise in a single or distinct clusters. The equivalent widths of the WR features in A2 --- including the CIV 5808 complex which we detect in this object for the first time --- are larger than previously observed in other WR galaxies. Models with sub-solar metallicity, as inferred from the nebular emission lines of this galaxy, predict much lower equivalent widths. On the ``clean'' side of A1, opposite to A2, we find no evidence for radial gradients in the observed stellar population at 0.05"<R<0.40" (~0.5 to 5 pc), neither in broad-band, low-resolution, spectra nor in medium-resolution spectra of the infrared CaII triplet.Comment: 5 pages, accepted for publication in ApJ Le

Numerical analysis of the grain size distribution in the activation of dry debris flow by means of DEM

El flujo de detritos es un proceso de naturaleza granular que ha sido abordado ampliamente bajo metodologías basadas en el medio continuo. Sin embargo, estas aproximaciones simplifican la realidad granular del suelo. Como material granular, la granulometría puede gobernar el comportamiento de este movimiento desagregado de masa. Es posible estudiar este comportamiento en términos del ángulo máximo alcanzado (θ), la energía cinética (Ek) y la profundidad de flujo (Fd) con el fin de establecer condiciones potenciales de falla, así como sus capacidades de daño. Para abordarlo se hace uso del método de elementos discretos, desarrollado por [1], bajo un estudio paramétrico en el cual se varían los parámetros de la granulometría: el tamaño medio del grano (d50), el coeficiente de curvatura (Cu) y el tamaño máximo de la muestra (dmax). Los resultados muestran que existe una influencia apreciable y una estrecha relación en los parámetros Ek y Fd. Con respecto al θ alcanzado en superficie se tiene una variación de menos de 5° para valores extremos de d50. Con esto, se muestra que la granulometría puede ser un factor importante que influye en la generación de flujos de detritos y se encuentran relacionadas cercanamente.Debris flow is a process of granular nature that has been widely analysed with methodologies based upon continuum mechanics. However, those approaches do not take into account the real granular condition of the soil. Grain size distribution exerts an important control on the movement of debris flows. This behaviour can be studied by analyzing three variables: maximum tilt angle (θ), kinetic energy (Ek) and flow depth (Fd). These variables allow to obtain a deeper insight into the conditions that trigger the failure of slopes and its subsequent capacity of damage. This research resorts to the use of the discrete element technique, developed by [1], performing a parametrical study of the parameters controlling grain size distributions like: mean size (d50), coefficient of curvature (Cu) and maximum size (dmax). The results showed an important influence and also a strong interaction between Ek and Fd on the onset of granular flows. The angle θ reached on the surface has a variation less than 5º with extreme values of d50. Results reported herein, allow to recognize the influence of grain size distribution on the triggering of slides of granular materials

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP)

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01–1.27], p = 0.03), (OR 1.14 95% CI [1.03–1.26], p = 0.009), (OR 1.1 95% CI [1.01–1.22], p = 0.039) and (OR 1.13 95% CI [1.03–1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the spanish post–heart transplant tumour registry

[Abstract] Background. Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods. This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results. Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions. Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively

Crustal Architecture at the Collision Zone Between Rivera and North American Plates at the Jalisco Block: Tsujal Project

Processing and analysis of new multichannel seismic records, coincident with wide-angle seismic profiles, acquired in the framework of the TsuJal project allow us to investigate in detail the complex structure of the oceanic domain in the collision zone between Rivera Plate and Block Jalisco at its northern termination. The subducting Rivera Plate, which is overridden by the North American Plate–Jalisco Block, is clearly identified up to 21.5°N (just south of Maria Magdalena Island) as a two clear reflections that we interpret as the interplate and Moho discontinuities. North of the Tres Marias Islands the seismic images display a different tectonic scenario with structures that are consistent with large faulting and rifted margin. A two-dimensional velocity approach for the crustal geometry is achieved using joint refraction/reflection travel time tomography, the uncertainty of the results is assessed by means of Monte Carlo analysis. Our results show an average oceanic crustal thickness of 6–7 km with a moderate increase towards the Jalisco Block, an anomalous thick layers (~3.0 km) displaying a relatively low velocity (~5.5 km/s) underneath Maria Magdalena Rise, and an estimated Moho depth deeper than 15 km in the collision zone between Rivera Plate and Jalisco Block. We have also determined an anomalous crust on the western flank of the Tres Marias Islands, which may be related to the initial phases of continental breakup of the Baja California Peninsula and Mexico mainland. High-resolution bathymetry provides remarkable images of intensive slope instabilities marked by relatively large slides scars of more than 40 km2 extent, and mass-wasting deposits probably triggered by the intense seismicity in the area.Consejo Nacional de Ciencia y Tecnología (CONACYT) –FOMIXJalGobierno de EspañaGobierno del Estado de JaliscoUniversidad Nacional Autonoma de MexicoAgencia Estatal de Investigación (España)Programa Ramón y CajalDepto. de Física de la Tierra y AstrofísicaFac. de Ciencias FísicasTRUEpu

Circulating adrenomedullin in cirrhosis: relationship to hyperdynamic circulation

BACKGROUND/AIMS: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. METHODS: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. RESULTS: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p<0.02) and was directly correlated with the Pugh score (r: 0.6; p: 0.01), inversely correlated with the creatinine clearance (r: -0.6; p<0.01) and tended to inversely correlate with systemic vascular resistance index (r: -0.46; p: 0.07). There were no portal-peripheral differences in adrenomedullin levels. Transjugular intrahepatic portosystemic shunt insertion did not induce changes in the peripheral concentration of adrenomedullin, but baseline values of this hormone predicted the degree of hyperdynamic circulation after TIPS. CONCLUSIONS: Circulating adrenomedullin is increased in cirrhosis. These levels increase with the severity of the disease, especially in patients with hepatorenal syndrome. This peptide may contribute to vasodilation of cirrhosis

Skin gene therapy for acquired and inherited disorders

The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).Our work is supported by grants SAF-2004-07717 from Ministerio de Ciencia y Tecnología (Spain) and LSHG-512073 from UE to M. Del Rio, LSHG-503447 from UE to J.L. Jorcano and LSHG-512102 from UE to F. Larcher. We express our gratitude to Dr. Y. Gache, Dr. F. Spirito and Dr. G. Meneguzzi for providing EM pictures to illustrate this work

Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study

[Abstract] Chronic kidney disease (CKD) is staged on the basis of glomerular filtration rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD) in heart transplant (HT) patients is often evaluated solely in terms of serum creatinine (SCr). In a cross-sectional, 14-center study of 1062 stable adult HT patients aged 59.1 ± 12.5 yr (82.3% men), RD was graded as absent-or-mild (AoM), moderate, or severe (this last including dialysis and kidney graft) by two classifications: SCr-RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR-RD (eGFR cutoffs 60 and 30 mL/min/1.73 m2). SCr-RD was AoM in 68.5% of patients, moderate in 24.9%, and severe in 6.7%; eGFR-RD, AoM in 38.6%, moderate in 52.2%, severe in 9.2%. Among patients evaluated 9.5 yr post-HT (the periods defined by time-since-transplant quartiles), AoM/moderate/severe RD prevalences were 9.5, SCr-RD 58/32/10%, eGFR-RD 32/52/16%. The prevalence of severe RD increases with time since transplant. If the usual CKD stages are appropriate for HT patients, the need for less nephrotoxic immunosuppressants and other renoprotective measures is greater than is suggested by direct SCr-based grading, which should be abandoned as excessively insensitive

Malignancy after heart transplantation: incidence, prognosis and risk factors

[Abstract] The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984–2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors