605 research outputs found
Rescue of endemic states in interconnected networks with adaptive coupling
We study the Susceptible-Infected-Susceptible model of epidemic spreading on two layers of networks interconnected by adaptive links, which are rewired at random to avoid contacts between infected and susceptible nodes at the interlayer. We find that the rewiring reduces the effective connectivity for the transmission of the disease between layers, and may even totally decouple the networks. Weak endemic states, in which the epidemics spreads when the two layers are interconnected but not in each layer separately, show a transition from the endemic to the healthy phase when the rewiring overcomes a threshold value that depends on the infection rate, the strength of the coupling and the mean connectivity of the networks. In the strong endemic scenario, in which the epidemics is able to spread on each separate network -and therefore on the interconnected system- the prevalence in each layer decreases when increasing the rewiring, arriving to single network values only in the limit of infinitely fast rewiring. We also find that rewiring amplifies finite-size effects, preventing the disease transmission between finite networks, as there is a non zero probability that the epidemics stays confined in only one network during its lifetime
Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis
The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 mÂČ). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates
Molecular Dynamics Simulation of Spinodal Decomposition in Three-Dimensional Binary Fluids
Using large-scale molecular dynamics simulations of a two-component
Lennard-Jones model in three dimensions, we show that the late-time dynamics of
spinodal decomposition in concentrated binary fluids reaches a viscous scaling
regime with a growth exponent , in agreement with experiments and a
theoretical analysis for viscous growth.Comment: 4 pages, 3 figure
Statistical-Mechanical Measure of Stochastic Spiking Coherence in A Population of Inhibitory Subthreshold Neurons
By varying the noise intensity, we study stochastic spiking coherence (i.e.,
collective coherence between noise-induced neural spikings) in an inhibitory
population of subthreshold neurons (which cannot fire spontaneously without
noise). This stochastic spiking coherence may be well visualized in the raster
plot of neural spikes. For a coherent case, partially-occupied "stripes"
(composed of spikes and indicating collective coherence) are formed in the
raster plot. This partial occupation occurs due to "stochastic spike skipping"
which is well shown in the multi-peaked interspike interval histogram. The main
purpose of our work is to quantitatively measure the degree of stochastic
spiking coherence seen in the raster plot. We introduce a new spike-based
coherence measure by considering the occupation pattern and the pacing
pattern of spikes in the stripes. In particular, the pacing degree between
spikes is determined in a statistical-mechanical way by quantifying the average
contribution of (microscopic) individual spikes to the (macroscopic)
ensemble-averaged global potential. This "statistical-mechanical" measure
is in contrast to the conventional measures such as the "thermodynamic" order
parameter (which concerns the time-averaged fluctuations of the macroscopic
global potential), the "microscopic" correlation-based measure (based on the
cross-correlation between the microscopic individual potentials), and the
measures of precise spike timing (based on the peri-stimulus time histogram).
In terms of , we quantitatively characterize the stochastic spiking
coherence, and find that reflects the degree of collective spiking
coherence seen in the raster plot very well. Hence, the
"statistical-mechanical" spike-based measure may be used usefully to
quantify the degree of stochastic spiking coherence in a statistical-mechanical
way.Comment: 16 pages, 5 figures, to appear in the J. Comput. Neurosc
Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study
In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with â„1 prior line received Rd (lenalidomide, 25 mg, on Days 1â21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35â0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10â5 ; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31â0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42â0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse
Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with non-intensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone.
Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after 2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit-risk profile and should be considered an appropriate treatment option for patients with 1 or 2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide
Lattice-gas simulations of Domain Growth, Saturation and Self-Assembly in Immiscible Fluids and Microemulsions
We investigate the dynamical behavior of both binary fluid and ternary
microemulsion systems in two dimensions using a recently introduced
hydrodynamic lattice-gas model of microemulsions. We find that the presence of
amphiphile in our simulations reduces the usual oil-water interfacial tension
in accord with experiment and consequently affects the non-equilibrium growth
of oil and water domains. As the density of surfactant is increased we observe
a crossover from the usual two-dimensional binary fluid scaling laws to a
growth that is {\it slow}, and we find that this slow growth can be
characterized by a logarithmic time scale. With sufficient surfactant in the
system we observe that the domains cease to grow beyond a certain point and we
find that this final characteristic domain size is inversely proportional to
the interfacial surfactant concentration in the system.Comment: 28 pages, latex, embedded .eps figures, one figure is in colour, all
in one uuencoded gzip compressed tar file, submitted to Physical Review
Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis
Light chain (AL) amyloidosis is caused by a small B-cell clone producing light chains that form amyloid deposits and cause organ dysfunction. Chemotherapy aims at suppressing the production of the toxic light chain (LC) and restore organ function. However, even complete hematologic response (CR), defined as negative serum and urine immunofixation and normalized free LC ratio, does not always translate into organ response. Next-generation flow (NGF) cytometry is used to detect minimal residual disease (MRD) in multiple myeloma. We evaluated MRD by NGF in 92 AL amyloidosis patients in CR. Fifty-four percent had persistent MRD (median 0.03% abnormal plasma cells). There were no differences in baseline clinical variables in patients with or without detectable MRD. Undetectable MRD was associated with higher rates of renal (90% vs 62%, pâ=â0.006) and cardiac response (95% vs 75%, pâ=â0.023). Hematologic progression was more frequent in MRD positive (0 vs 25% at 1 year, pâ=â0.001). Altogether, NGF can detect MRD in approximately half the AL amyloidosis patients in CR, and persistent MRD can explain persistent organ dysfunction. Thus, this study supports testing MRD in CR patients, especially if not accompanied by organ response. In case MRD persists, further treatment could be considered, carefully balancing residual organ damage, patient frailty, and possible toxicity
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