An analysis of some graph theoretical cluster techniques

Graph theoretic cluster techniques for automatic generation of information retrieval systems thesaur

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

Differential expression of the Bcl-2 and Bax isoforms in CD19 positive B-lymphocytes isolated from patients diagnosed with chronic lymphocytic leukaemia

Aim: To examine the relative gene expression levels of the anti-apoptotic Bcl-2a and ß isoforms and the pro-apoptotic Baxa and ß isoforms in patients with chronic lymphocytic leukaemia (CLL) and healthy controls (HC). Methods: Peripheral blood was obtained from 36 patients diagnosed with CLL and 10 HC. CD19+ B-lymphocytes were isolated using an antibody coupled magnetic bead isolation system; from these cells the total RNA was isolated and purified. The relative levels of gene expression were examined by quantitative real-time polymerase chain reaction (qReTi-PCR) using primers specific for each isoform. Results: Bcl-2a and Baxa are expressed at higher levels than their ß-isoforms in CLL and HC. Bcl-2a, Bcl-2ß and Baxb expression is increased in CLL while Bax-a is expressed at similar levels to HC. The Bcl-2a/Bcl-2ß ratio is similar in CLL and HC. The Bcl-2a/Baxa ratio is increased in CLL when compared with HC. Conclusion: Bcl-2a and Baxa appear to be the dominant antiand pro-apoptotic isoforms in CLL. The Bcl-2a/Baxa ratio is increased in CLLwhile the Bcl-2a/Bcl-2ß ratio is similar to HC

Incidence of c-Cbl mutations in human acute myeloid leukaemias in an Australian patient cohort

Aim: The aim of this study was to investigate the incidence and characteristics of c-Cbl mutations in acute myeloid leukaemias (AMLs) from an Australian patient cohort. Two initial studies examining c-Cbl mutations in AML, one from Germany and one from the US, found vastly different incidences of mutations (0.6% compared to 33%, respectively). Therefore, it was important to determine the incidence and characteristics of c-Cbl mutations in a cohort of Australian AML patients. Methods: Ninety patients with AML were investigated. The open reading frame between exons 4 and 11 of the c-Cbl gene was analysed by reverse-transcription polymerase chain reaction (RT-PCR), nested PCR and DNA sequencing. Results: We found four AML samples (4/90; 4.44%) with distinct c-Cbl deletions involving exons 6 to 9. Sample 10 [AML with t(8;21)] showed two deletions [c.870-1007del] and [c.1106-1228del]. Sample 81 (AML with minimal differentiation) showed a large deletion [c.1008-1431del] causing a frameshift and a premature stop codon. Sample 82 (AML without maturation) showed two deletions [c.928- 1307del] and [c.1385-1431del] also causing a frameshift and a premature stop codon. Sample 84 (AML with myelodysplasia related changes) showed a large deletion [c.964-1380del]. Conclusion: Although our data indicate that c-Cbl deletions are not common in AML in the Australian population, they do raise the possibility that c-Cbl mutations might contribute to the pathogenesis of these AML cases. © 2011 Royal College of Pathologists of Australasia