232 research outputs found

    Field line distribution of mass density at geostationary orbit

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    The distribution of mass density along the field lines affects the ratios of toroidal (azimuthally oscillating) Alfv\u27{e}n frequencies, and given the ratios of these frequencies we can get information about that distribution. Here we assume the commonly used power law form for the field line distribution, rho_{m} = rho_{m,eq} ( L R_{E} /R )^alpha, where rho_{m,eq} is the value of the mass density rho_{m} at the magnetic equator, L is the L shell, R_{E} is the Earth\u27s radius, R is the geocentric distance to a point on the field line, and alpha is the power law coefficient. Positive values of alpha indicate that rho_{m} increases away from the magnetic equator, zero value indicates that rho_{m} is constant along the magnetic field line, and negative alpha indicates that there is a local peak in rho_{m} at the magnetic equator. Using 12 years of observations of toroidal Alfven frequencies by the Geostationary Operational Environmental Satellites (GOES), we study the typical dependence of inferred values of alpha on the magnetic local time (MLT), the phase of the solar cycle as specified by the F10.7 extreme ultraviolet solar flux, and geomagnetic activity as specified by the auroral electrojet (AE) index. Over the mostly dayside range of the observations, we find that alpha decreases with respect to increasing MLT and F10.7, but increases with respect to increasing AE. We develop a formula that depends on all three parameters, alpha_{3Dmodel} = 2.2 + 1.3 cos(MLT 15 degrees) + 0.0026 {AE} cos((MLT-0.8) 15 degrees) + 2.1 10^{-5} {AE} {F10.7} - 0.010 {F10.7},\r\nthat models the binned values of alpha within a standard deviation of 0.3. While we do not yet have a complete theoretical understanding of why alpha should depend on these parameters in such a way, we do make some observations and speculations about the causes. At least part of the dependence is related to that of rho_{m,eq}; higher alpha, corresponding to steeper variation with respect to MLAT, occurs when rho_{m,eq} is lower

    Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk

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    BACKGROUND: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). METHODS: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ\uae assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. RESULTS: After a median follow-up of 40.0\u2009months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6\u2009months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2\u2009months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. CONCLUSION: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014

    International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)

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    Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable

    Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma

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    The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m2 on D1 and D15 plus DXM 40 mg on D1, D8, D15, and D22 (arm A, n = 171) or DXM 40 mg on D1, D8, D15, and D22 (arm B, n = 84) q4wk. The primary endpoint was progression-free survival (PFS). Median PFS without disease progression (PD) confirmation (IRC assessment) was 2.6 months (arm A) and 1.7 months (arm B) (HR = 0.650; p = 0.0054). Median PFS with PD confirmation (investigator’s assessment) was 3.8 months (arm A) and 1.9 months (arm B) (HR = 0.611; p = 0.0040). Median overall survival (OS, intention-to-treat analysis) was 11.6 months (arm A) and 8.9 months (arm B) (HR = 0.797; p = 0.1261). OS improvement favoring arm A was found when discounting a crossover effect (37 patients crossed over from arm B to arm A) (two-stage method; HR = 0.622; p = 0.0015). The most common grade 3/4 treatment-related adverse events (% of patients arm A/arm B) were fatigue (10.8%/1.2%), myalgia (5.4%/0%), and nausea (3.6%/1.2%), being usually transient and reversible. The safety profile does not overlap with the toxicity observed with other agents used in multiple myeloma. In conclusion, efficacy data, the reassuring safety profile, and the novel mechanism of action of plitidepsin suggest that this combination can be an alternative option in patients with relapsed/refractory multiple myeloma after at least three prior therapy lines

    An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

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    So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

    Updated precision measurement of the average lifetime of B hadrons

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    The measurement of the average lifetime of B hadrons using inclusively reconstructed secondary vertices has been updated using both an improved processing of previous data and additional statistics from new data. This has reduced the statistical and systematic uncertainties and gives \tau_{\mathrm{B}} = 1.582 \pm 0.011\ \mathrm{(stat.)} \pm 0.027\ \mathrm{(syst.)}\ \mathrm{ps.} Combining this result with the previous result based on charged particle impact parameter distributions yields \tau_{\mathrm{B}} = 1.575 \pm 0.010\ \mathrm{(stat.)} \pm 0.026\ \mathrm{(syst.)}\ \mathrm{ps.

    Observation of a new Xi(b) baryon

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    The first observation of a new b baryon via its strong decay into Xi(b)^- pi^+ (plus charge conjugates) is reported. The measurement uses a data sample of pp collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 5.3 inverse femtobarns. The known Xi(b)^- baryon is reconstructed via the decay chain Xi(b)^- to J/psi Xi^- to mu^+ mu^- Lambda^0 pi^-, with Lambda^0 to p pi^-. A peak is observed in the distribution of the difference between the mass of the Xi(b)^- pi^+ system and the sum of the masses of the Xi(b)^- and pi^+, with a significance exceeding five standard deviations. The mass difference of the peak is 14.84 +/- 0.74 (stat.) +/- 0.28 (syst.) MeV. The new state most likely corresponds to the J^P=3/2^+ companion of the Xi(b).Comment: Submitted to Physical Review Letter
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