On differential rotation and overshooting in solar-like stars

This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.We seek to characterize how the change of global rotation rate influences the overall dynamics and large scale flows arising in the convective envelopes of stars covering stellar spectral types from early G to late K. We do so through numerical simulations with the ASH code, where we consider stellar convective envelopes coupled to a radiative interior with various global properties. As solar-like stars spin down over the course of their main sequence evolution, such change must have a direct impact on their dynamics and rotation state. We indeed find that three main states of rotation may exist for a given star: anti-solar-like (fast poles, slow equator), solar-like (fast equator, slow poles), or a cylindrical rotation profile. Under increasingly strict rotational constraints, the latter profile can further evolve into a Jupiter-like profile, with alternating prograde and retrograde zonal jets. We have further assessed how far the convection and meridional flows overshoot into the radiative zone and investigated the morphology of the established tachocline. Using simple mixing length arguments, we are able to construct a scaling of the fluid Rossby number $R_{of} = \tilde{\omega}/2\Omega_* \sim \tilde{v}/2\Omega_* R_*$, which we calibrate based on our 3-D ASH simulations. We can use this scaling to map the behavior of differential rotation versus the global parameters of stellar mass and rotation rate. Finally, we isolate a region on this map ($R_{of} \gtrsim 1.5-2$) where we posit that stars with an anti-solar differential rotation may exist in order to encourage observers to hunt for such targets.We acknowledge funding by ERC STARS2 207430 grant, ANR Blanc Toupies SIMI5-6 020 01, INSU/PNST, CNES SolarOrbiter, PLATO and GOLF grants, FP7 SpaceInn 312844 grant, and NASA grants NNX11AJ36G, NNX13AG18G and NNX16AC92G. K. C. Augustson is funded through the ERC SPIRE 647383 grant. A. Strugarek acknowledges support from the Canadian Institute of Theoretical Astrophysics (National Fellow), from Canadas Natural Sciences and Engineering Research Council and from CNES postdoctoral fellowship

Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS

BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire. OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT. METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT. Neurological function was assessed by the EDSS before ASCT and for three years post-ASCT. RESULTS: CD4+ T-cells fell significantly post-transplant and did not return to baseline levels. Recent thymic emigrants and naïve T-cells fell sharply post-transplant but returned to baseline by nine months and twelve months, respectively. T-regulatory cells declined post-transplant and did not return to baseline levels. Th1 and Th2 cells did not change significantly while Th17 cells fell post-transplant but recovered to baseline by six months. Neurological function remained stable in the majority of patients. Progression-free survival was 69% at three years. CONCLUSION: This study demonstrates major changes in the composition of lymphocyte subsets following ASCT for progressive MS. In particular, ablation and subsequent recovery of thymic output is consistent with the concept that ASCT can reset the immune repertoire in MS patients

Design and development of the Australian and New Zealand (ANZ) myeloma and related diseases registry

© 2016 The Author(s). Background: Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR) was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. Methods: The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. Results: More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and 'real world' outcome data, to support the conduction of high quality studies. In addition, the Myeloma 1000 sub-study is establishing a repository of paired peripheral blood specimens from registry patients to study mechanisms underlying disease progression. Conclusion: Establishment of the MRDR has been challenging, but it is a valuable investment that will provide a platform for coordinated national and international collaboration for clinical research in PCD in ANZ

U.S./Russian lab-to-lab materials protection, control and accounting program efforts at the Institute of Inorganic Materials. Revision 1

The All-Russian Scientific Research Institute of Inorganic Materials (VNIINM) performs research in nuclear power reactor fuel, spent fuel reprocessing and waste management, materials science of fissionable and reactor structural materials, metallurgy, superconducting materials, and analytical sciences. VNIINM supports the Ministry of Atomic Energy of the Russian Federation (MINATOM) in technologies for fabrication and processing of nuclear fuel. As a participant in the US/Russian Lab-to-Lab nuclear materials protection, control and accounting (MPC and A) program, VNIINM is providing support for measurements of nuclear materials in bulk forms by developing specifications, test and evaluation, certification, and implementation of measurement methods for such materials. In 1996, VNIINM will be working with Brookhaven staff in developing and documenting material control and accounting requirements for nuclear materials in bulk form, Livermore and Los Alamos staff in testing and evaluating gamma-ray spectrometry methods for bulk materials, Los Alamos staff in test and evaluation of neutron-coincidence counting techniques, Oak Ridge staff in accounting of bulk materials with process instrumentation, and Pacific Northwest staff on automating VNIINM`s coulometric titration system. In addition, VNIINM will develop a computerized accounting system for nuclear material within VNIINM and their storage facility. The paper will describe the status of this work and anticipated progress in 1996

Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis

PURPOSE: Oral melphalan and dexamethasone (MDex) were considered a standard of care in light-chain (AL) amyloidosis. In the past decade, bortezomib has been increasingly used in combination with alkylating agents and dexamethasone. We prospectively compared the efficacy and safety of MDex and MDex with the addition of bortezomib (BMDex). METHODS: This was a phase III, multicenter, randomized, open-label trial. Patients were stratified according to cardiac stage. Patients with advanced cardiac stage (stage IIIb) amyloidosis were not eligible. The primary end point was hematologic response rate at 3 months. This trial is registered with ClinicalTrials.gov identifier NCT01277016. RESULTS: A total of 109 patients, 53 in the BMDex and 56 in the MDex group, received ≥ 1 dose of therapy (from January 2011 to February 2016). Hematologic response rate at 3 months was higher in the BMDex arm (79% v 52%; P = .002). Higher rates of very good partial or complete response rates (64% v 39%; hazard ratio [HR], 2.47; 95% CI, 1.30 to 4.71) and improved overall survival, with a 2-fold decrease in mortality rate (HR, 0.50; 95% CI, 0.27 to 0.90), were observed in the BMDex arm. Grade 3 and 4 adverse events (the most common being cytopenia, peripheral neuropathy, and heart failure) were more common in the BMDex arm, occurring in 20% versus 10% of cycles performed. CONCLUSION: BMDex improved hematologic response rate and overall survival. To our knowledge, this is the first time a controlled study has demonstrated a survival advantage in AL amyloidosis. BMDex should be considered a new standard of care for AL amyloidosis

Multisite spectroscopic seismic study of the beta Cep star V2052 Oph: inhibition of mixing by its magnetic field

We used extensive ground-based multisite and archival spectroscopy to derive observational constraints for a seismic modelling of the magnetic beta Cep star V2052 Ophiuchi. The line-profile variability is dominated by a radial mode (f_1=7.14846 d^{-1}) and by rotational modulation (P_rot=3.638833 d). Two non-radial low-amplitude modes (f_2=7.75603 d^{-1} and f_3=6.82308 d^{-1}) are also detected. The four periodicities that we found are the same as the ones discovered from a companion multisite photometric campaign (Handler et al. 2012) and known in the literature. Using the photometric constraints on the degrees l of the pulsation modes, we show that both f_2 and f_3 are prograde modes with (l,m)=(4,2) or (4,3). These results allowed us to deduce ranges for the mass (M \in [8.2,9.6] M_o) and central hydrogen abundance (X_c \in [0.25,0.32]) of V2052 Oph, to identify the radial orders n_1=1, n_2=-3 and n_3=-2, and to derive an equatorial rotation velocity v_eq \in [71,75] km s^{-1}. The model parameters are in full agreement with the effective temperature and surface gravity deduced from spectroscopy. Only models with no or mild core overshooting (alpha_ov \in [0,0.15] local pressure scale heights) can account for the observed properties. Such a low overshooting is opposite to our previous modelling results for the non-magnetic beta Cep star theta Oph having very similar parameters, except for a slower surface rotation rate. We discuss whether this result can be explained by the presence of a magnetic field in V2052 Oph that inhibits mixing in its interior.Comment: 12 pages, 6 figures and 5 tables; accepted for publication in MNRAS on 2012 August 1

Comorbidity as a prognostic variable in multiple myeloma: comparative evaluation of common comorbidity scores and use of a novel MM–comorbidity score

Comorbidities have been demonstrated to affect progression-free survival (PFS) and overall survival (OS), although their impact in multiple myeloma (MM) patients is as yet unsettled. We (1) assessed various comorbidities, (2) compared established comorbidity indices (CIs; Charlson comorbidity index (CCI), hematopoietic cell transplantation-specific comorbidity index (HCT-CI)), Kaplan Feinstein (KF) and Satariano index (SI) and (3) developed a MM-CI (Freiburger comorbidity index, FCI) in 127 MM patients. Univariate analysis determined moderate or severe pulmonary disease (hazard ratio (HR): 3.5, P<0.0001), renal impairment (via estimated glomerular filtration rate (eGFR); HR: 3.4, P=0.0018), decreased Karnofsky Performance Status (KPS, HR: 2.7, P=0.0004) and age (HR: 2, P=0.0114) as most important variables for diminished OS. Through multivariate analysis, the eGFR ⩽30 ml/min/1.73m2, impaired lung function and KPS ⩽70% were significant for decreased OS, with HRs of 2.9, 2.8 and 2.2, respectively. Combination of these risk factors within the FCI identified significantly different median OS rates of 118, 53 and 25 months with 0, 1 and 2 or 3 risk factors, respectively, (P<0.005). In light of our study, comorbidities are critical prognostic determinants for diminished PFS and OS. Moreover, comorbidity scores are important treatment decision tools and will be valuable to implement into future analyses and clinical trials in MM

Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data

<p>Abstract</p> <p>Background</p> <p>African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from <it>Kick It at Swope III </it>(KIS-III), the first treatment study of bupropion for African American light smokers.</p> <p>Methods</p> <p>Five hundred forty African American light smokers were randomly assigned to receive bupropion (150mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up.</p> <p>Results</p> <p>Of 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4ppm (range 1-55) and a mean serum cotinine of 275.8ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high.</p> <p>Conclusion</p> <p>KIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="URL">NCT00666978</a></p