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"Ludwig, H"
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Solar Chemical Abundances Determined with a CO5BOLD 3D Model Atmosphere
In the last decade, the photospheric solar metallicity as determined from spectroscopy experienced a remarkable downward revision. Part of this effect can be attributed to an improvement of atomic data and the inclusion of NLTE computations, but also the use of hydrodynamical model atmospheres seemed to play a role. This “decrease” with time of the metallicity of the solar photosphere increased the disagreement with the results from helioseismology. With a CO
5
BOLD 3D model of the solar atmosphere, the CIFIST team at the Paris Observatory re-determined the photospheric solar abundances of several elements, among them C, N, and O. The spectroscopic abundances are obtained by fitting the equivalent width and/or the profile of observed spectral lines with synthetic spectra computed from the 3D model atmosphere. We conclude that the effects of granular fluctuations depend on the characteristics of the individual lines, but are found to be relevant only in a few particular cases. 3D effects are not responsible for the systematic lowering of the solar abundances in recent years. The solar metallicity resulting from this analysis is
Z
=0.0153,
Z
/
X
=0.0209.
Journal Article
Decision avoidance and post-decision regret: A systematic review and meta-analysis
Decision Avoidance (DA) strategies allow people to forego or abandon effortful deliberation by postponing, bypassing, or delegating a decision. DA is thought to reduce regret, primarily by allowing decision makers to evade personal responsibility for potential negative outcomes. We tested this relation between DA and post-decision regret in a multilevel meta-analysis of 59 effect estimates coming from 13 papers. Five DA strategies were considered: status quo preservation, action omission, inaction inertia, choice delegation and choice deferral. Across all effects and DA strategies, there was a non-significant trend toward DA reducing regret (Hedges’ g = -0.23, p = 0.063). When assessing individual strategies, we found that only status quo preservation reduced regret reliably (Hedges’ g = -0.45, p = 0.006). The relationship between DA and regret was unclear for the other DA strategies. We tested a number of moderators for the effect. Only ‘previous experience’ (i.e., the outcome of a previous decision) influenced the relation between DA and regret reliably. That is, if participants choose the DA option when the same choice previously led to a negative outcome, regret is actually enhanced. Overall, there is clear evidence that status quo preservation can reduce regret, but it is currently unclear whether the same holds for other DA strategies.
Journal Article
Solar Science with the Atacama Large Millimeter/Submillimeter Array—A New View of Our Sun
The Atacama Large Millimeter/submillimeter Array (ALMA) is a new powerful tool for observing the Sun at high spatial, temporal, and spectral resolution. These capabilities can address a broad range of fundamental scientific questions in solar physics. The radiation observed by ALMA originates mostly from the chromosphere—a complex and dynamic region between the photosphere and corona, which plays a crucial role in the transport of energy and matter and, ultimately, the heating of the outer layers of the solar atmosphere. Based on first solar test observations, strategies for regular solar campaigns are currently being developed. State-of-the-art numerical simulations of the solar atmosphere and modeling of instrumental effects can help constrain and optimize future observing modes for ALMA. Here we present a short technical description of ALMA and an overview of past efforts and future possibilities for solar observations at submillimeter and millimeter wavelengths. In addition, selected numerical simulations and observations at other wavelengths demonstrate ALMA’s scientific potential for studying the Sun for a large range of science cases.
Journal Article
Carfilzomib–dexamethasone vs bortezomib–dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR
The randomized phase 3 study ENDEAVOR demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (MM). We conducted a preplanned subgroup analysis of ENDEAVOR to evaluate Kd vs Vd by cytogenetic risk. Of 785 patients with known cytogenetics, 210 (27%) had high-risk cytogenetics (Kd,
n
=97 (25%); Vd,
n
=113 (28%)) and 575 (73%) had standard-risk cytogenetics (Kd,
n
=284 (75%); Vd,
n
=291 (72%)). Median PFS in the high-risk group was 8.8 months for Kd vs 6.0 months for Vd (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.45–0.92;
P
=0.0075). Median PFS in the standard-risk group was not estimable for Kd vs 10.2 months for Vd (HR, 0.44; 95% CI, 0.33–0.58;
P
<0.0001). Overall response rates were 72.2% (Kd) vs 58.4% (Vd) in the high-risk group and 79.2% (Kd) vs 66.0% (Vd) in the standard-risk group. In the high-risk group, 15.5% (Kd) vs 4.4% (Vd) achieved a complete response (CR) or better. In the standard-risk group, 13.0% (Kd) vs 7.9% (Vd) achieved ⩾CR. This preplanned subgroup analysis found that Kd was superior to Vd in relapsed or refractory MM, regardless of cytogenetic risk.
Journal Article
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management
Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2–3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1–2% per year for the next 10 years. Testing should be done 2–3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4–6 months for 1 year and, if stable, every 6–12 months.
Journal Article
Foveal analysis and peripheral selection during active visual sampling
Human vision is an active process in which information is sampled during brief periods of stable fixation in between gaze shifts. Foveal analysis serves to identify the currently fixated object and has to be coordinated with a peripheral selection process of the next fixation location. Models of visual search and scene perception typically focus on the latter, without considering foveal processing requirements. We developed a dual-task noise classification technique that enables identification of the information uptake for foveal analysis and peripheral selection within a single fixation. Human observers had to use foveal vision to extract visual feature information (orientation) from different locations for a psychophysical comparison. The selection of to-be-fixated locations was guided by a different feature (luminance contrast). We inserted noise in both visual features and identified the uptake of information by looking at correlations between the noise at different points in time and behavior. Our data show that foveal analysis and peripheral selection proceeded completely in parallel. Peripheral processing stopped some time before the onset of an eye movement, but foveal analysis continued during this period. Variations in the difficulty of foveal processing did not influence the uptake of peripheral information and the efficacy of peripheral selection, suggesting that foveal analysis and peripheral selection operated independently. These results provide important theoretical constraints on how to model target selection in conjunction with foveal object identification: in parallel and independently.
Journal Article
Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study
The randomized phase 3 ENDEAVOR study (
N
=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ⩾2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (⩾2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide.
Journal Article
A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)
This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m
2
on days 1 and 2 of cycle 1; 27 mg/m
2
thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (
n
=157) or control (
n
=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4–14.4) vs 10.0 months (95% CI 7.7–12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760–1.249;
P
=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.
Journal Article
International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders
The serum immunoglobulin-free light chain (FLC) assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.
Journal Article