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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 ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 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, 0.35–0.55; 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 (10–5; 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, 0.31–0.50; 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, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse. © 2020, The Author(s).

In this paper, the robust sliding mode control based on reduced order observer is proposed to overcome the model imperfections in ultra-precision positioning system. The reduced order sliding mode observer enables the states and the estimated outputs to be available for controller design. The manifold of the sliding mode control is composed of the estimated output only instead of system states. Using the reduced order observer, the sliding mode control is designed in output feedback form. The effectiveness of the proposed control algorithm has been proved from the application of an ultra-precision stage.

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size. © 2015 Nature America, Inc.

A micromechanics-based durability model was developed to predict the flexural mechanical properties of thin sheet cementitious composites reinforced with refined and unrefined cellulose fibers when the composite was tested dry, wet, and accelerated (carbonation) aged. The model is based on fracture mechanics and directly links the changes in material structure resulting from environmental deterioration processes to composite flexural mechanical properties. The model was used as a tool to estimate quantitatively cellulose fiber-matrix interfacial microparameters that were too difficult to measure experimentally. Reasonable agreement was found between model predictions and experimentally determined trends in composite flexural mechanical properties and mode of cellulose fiber failure (pullout or rupture) as a function of environment. This supports the validity of the proposed micromechanical modeling parameters.

This work investigated numerically the effects of the order of layers in 1-D magnetic photonic crystals (MPCs), composed of Al 2 O 3 and Bi:YIG multilayers. The perfectly periodic structures give the same transmittance spectra, independent of the order of layers. A defect layer results in a low reflectance within the bandgap. The order of layers in the MPCs, containing defect layers, affects the transfer behavior. Keeping the total number of defect layers the same, the more the magnetic defect layers, the larger the defect effects. Compared with the dielectric defect layers, the magnetic defect layers bring about a broader width of photonic bandgap, and a larger transmittance at the defect modes.

It is well known that experimentally induced cochlear damage produces structural, physiological, and biochemical alterations in neurons of the cochlear nucleus. In contrast, much less is known with respect to the naturally occurring cochlear pathology presented by congenital deafness. The present study attempts to relate organ of Corti structure and auditory nerve activity to the morphology of primary synaptic endings in the cochlear nucleus of congenitally deaf white cats. Our observations reveal that the amount of sound-evoked spike activity in auditory nerve fibers influences terminal morphology and synaptic structure in the anteroventral cochlear nucleus. Some white cats had no hearing. They exhibited severely reduced spontaneous activity and no sound-evoked activity in auditory nerve fibers. They had no recognizable organ of Corti, presented .90% loss of spiral ganglion cells, and displayed marked structural abnormalities of endbulbs of Held and their synapses. Other white cats had partial hearing and possessed auditory nerve fibers with a wide range of spontaneous activity but elevated sound-evoked thresholds (60‐70 dB SPL). They also exhibited obvious abnormalities in the tectorial membrane, supporting cells, and Reissner’s membrane throughout the cochlear duct and had complete inner and outer hair cell loss in the base. The spatial distribution of spiral ganglion cell loss correlated with the pattern of hair cell loss. Primary neurons of hearing-impaired cats displayed structural abnormalities of their endbulbs and synapses in the cochlear nucleus which were intermediate in form compared to normal and totally deaf cats. Changes in endbulb structure appear to correspond to relative levels of deafness. These data suggest that endbulb structure is significantly influenced by sound-evoked auditory nerve activity. J. Comp. Neurol. 397:532‐548, 1998. r 1998 Wiley-Liss, Inc. Indexing terms: organ of Corti structure; auditory nerve fibers; terminal morphology

The dielectric properties of gamma-ray irradiated and thermally aged polyetheretherketone (PEEK) have been investigated. Results of the temperature dependency of the dielectric properties indicated that the glass transition temperature of the aged PEEK increased with radiation and thermal ageing. The frequency dependency of dielectric properties implied that the magnitude of radiation and thermal induced dipoles and ions increased as radiation and thermal ageing. The values of the relaxation intensity calculated using Cole-Cole's circular arc can be useful for the evaluation of the degradation level of PEEK.

Radiation effects on fire retardant properties of polychloroprene containing flame retardant additives were investigated. Ammonium polyphosphate, magnesium dihydrate, and antimony trioxide were selected as flame retardants. The limited oxygen index (LOI) and oxidative induction time (OIT) measurement were carried out as flame resistance tests for radiation degradation. The values of LOI increased with an increasing radiation dose due to the synergy effects between fire retardant and chlorine decomposed from CR. The values of DOT decreased with an increasing radiation dose because of dehydrochlorination and oxidation. Among the fire retardants, antimony trioxide showed the best radiation resistance and fire retardant characteristics.

For the normal location family the noncentrality parameter of the non-central X2 distribution admits a simple closed form representation through the normal centroid. Exploiting this relation, we show how the normal centroid facilitates the evaluation of the powers of the Pearson's X2 test and the Kolmogorov-Smirnov test.