Stellar turbulence and mode physics

An overview of selected topical problems on modelling oscillation properties in solar-like stars is presented. High-quality oscillation data from both space-borne intensity observations and ground-based spectroscopic measurements provide first tests of the still-ill-understood, superficial layers in distant stars. Emphasis will be given to modelling the pulsation dynamics of the stellar surface layers, the stochastic excitation processes and the associated dynamics of the turbulent fluxes of heat and momentum.Comment: Proc. HELAS Workshop on 'Synergies between solar and stellar modelling', eds M. Marconi, D. Cardini, M. P. Di Mauro, Astrophys. Space Sci., in the pres

Emissions Savings in the Corn-Ethanol Life Cycle from Feeding Coproducts to Livestock

Environmental regulations on greenhouse gas (GHG) emissions from corn (Zea mays L.)-ethanol production require accurate assessment methods to determine emissions savings from coproducts that are fed to livestock. We investigated current use of coproducts in livestock diets and estimated the magnitude and variability in the GHG emissions credit for coproducts in the corn-ethanol life cycle. The coproduct GHG emissions credit varied by more than twofold, from 11.5 to 28.3 g CO2e per MJ of ethanol produced, depending on the fraction of coproducts used without drying, the proportion of coproduct used to feed beef cattle (Bos taurus) vs. dairy or swine (Sus scrofa), and the location of corn production. Regional variability in the GHG intensity of crop production and future livestock feeding trends will determine the magnitude of the coproduct GHG offset against GHG emissions elsewhere in the corn-ethanol life cycle. Expansion of annual U.S. corn-ethanol production to 57 billion liters by 2015, as mandated in current federal law, will require feeding of coproduct at inclusion levels near the biological limit to the entire U.S. feedlot cattle, dairy, and swine herds. Under this future scenario, the coproduct GHG offset will decrease by 8% from current levels due to expanded use by dairy and swine, which are less efficient in use of coproduct than beef feedlot cattle. Because the coproduct GHG credit represents 19 to 38% of total life cycle GHG emissions, accurate estimation of the coproduct credit is important for determining the net impact of corn-ethanol production on atmospheric warming and whether corn-ethanol producers meet state- and national-level GHG emissions regulations

Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab

Background: Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods: A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results: A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions: These data suggest that long-term survival is possible after blinatumomab therapy. Lay Summary: Immuno-oncology therapies such as blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with blinatumomab

Clinical Science Unique risks for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery

Abstract BACKGROUND: The aim of this study was to identify unique risk factors for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery. METHODS: A multivariate logistic regression model predicting 30-day mortality was constructed for patients with end-stage renal disease undergoing nonemergent colorectal procedures. Data were obtained from the National Surgical Quality Improvement Program (2005Program ( -2010. RESULTS: Among the 394 patients analyzed, those with serum creatinine levels .7.5 mg/dL had .07 times the adjusted mortality risk of those with levels ,3.5 mg/dL. For colorectal surgery patients, the average serum creatinine level was 5.52 6 2.6 mg/dL, and mortality was 13% (n 5 50). CONCLUSIONS: High serum creatinine was associated with a lower risk for mortality in patients with end-stage renal disease, even though creatinine is often considered a risk factor for surgery. These results show how variables from a patient-centered subpopulation can differ in meaning from the general population. 4 This database is a tool that records perioperative risk factors for addressing surgical morbidity and mortality. Our objective was to use the NSQIP data to create a multivariate model to identify unique risk factors predicting mortality in patients with ESRD undergoing nonemergent colorectal procedures

Comparisons of Supergranule Characteristics During the Solar Minima of Cycles 22/23 and 23/24

Supergranulation is a component of solar convection that manifests itself on the photosphere as a cellular network of around 35 Mm across, with a turnover lifetime of 1-2 days. It is strongly linked to the structure of the magnetic field. The horizontal, divergent flows within supergranule cells carry local field lines to the cell boundaries, while the rotational properties of supergranule upflows may contribute to the restoration of the poloidal field as part of the dynamo mechanism that controls the solar cycle. The solar minimum at the transition from cycle 23 to 24 was notable for its low level of activity and its extended length. It is of interest to study whether the convective phenomena that influences the solar magnetic field during this time differed in character to periods of previous minima. This study investigates three characteristics (velocity components, sizes and lifetimes) of solar supergranulation. Comparisons of these characteristics are made between the minima of cycles 22/23 and 23/24 using MDI Doppler data from 1996 and 2008, respectively. It is found that whereas the lifetimes are equal during both epochs (around 18 h), the sizes are larger in 1996 (35.9 +/- 0.3 Mm) than in 2008 (35.0 +/- 0.3 Mm), while the dominant horizontal velocity flows are weaker (139 +/- 1 m/s in 1996; 141 +/- 1 m/s in 2008). Although numerical differences are seen, they are not conclusive proof of the most recent minimum being inherently unusual.Comment: 22 pages, 5 figures. Solar Physics, in pres

Enteropathogenic Escherichia coli (EPEC) inactivate innate immune responses prior to compromising epithelial barrier function

Enteropathogenic Escherichia coli (EPEC) infection of the human small intestine induces severe watery diarrhoea linked to a rather weak inflammatory response despite EPEC's in vivo capacity to disrupt epithelial barrier function. Here, we demonstrate that EPEC flagellin triggers the secretion of the pro-inflammatory cytokine, interleukin (IL)-8, from small (Caco-2) and large (T84) intestinal epithelia model systems. Interestingly, IL-8 secretion required basolateral infection of T84 cells implying that flagellin must penetrate the epithelial barrier. In contrast, apical infection of Caco-2 cells induced IL-8 secretion but less potently than basolateral infections. Importantly, infection of Caco-2, but not T84 cells rapidly inhibited IL-8 secretion by a mechanism dependent on the delivery of effectors through a translocation system encoded on the locus of enterocyte effacement (LEE). Moreover, EPEC prevents the phosphorylation-associated activation of multiple kinase pathways regulating IL-8 gene transcription by a mechanism apparently independent of LEE-encoded effectors and four non-LEE-encoded effectors. Crucially, our studies reveal that EPEC inhibits the capacity of the cells to secrete IL-8 in response to bacterial antigens and inflammatory cytokines prior to disrupting barrier function by a distinct mechanism. Thus, these findings also lend themselves to a plausible mechanism to explain the absence of a strong inflammatory response in EPEC-infected humans

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation (alloHSCT) have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR) or CR with partial hematologic recovery of peripheral blood counts (CRh) of 43% within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64) achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD) response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate) was 36% at 1 year and 18% at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31%) and 28 patients (44%), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade 64 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population

Stein's method on Wiener chaos

We combine Malliavin calculus with Stein's method, in order to derive explicit bounds in the Gaussian and Gamma approximations of random variables in a fixed Wiener chaos of a general Gaussian process. We also prove results concerning random variables admitting a possibly infinite Wiener chaotic decomposition. Our approach generalizes, refines and unifies the central and non-central limit theorems for multiple Wiener-It\^o integrals recently proved (in several papers, from 2005 to 2007) by Nourdin, Nualart, Ortiz-Latorre, Peccati and Tudor. We apply our techniques to prove Berry-Ess\'een bounds in the Breuer-Major CLT for subordinated functionals of fractional Brownian motion. By using the well-known Mehler's formula for Ornstein-Uhlenbeck semigroups, we also recover a technical result recently proved by Chatterjee, concerning the Gaussian approximation of functionals of finite-dimensional Gaussian vectors.Comment: 39 pages; Two sections added; To appear in PTR