The Influence of the Degree of Heterogeneity on the Elastic Properties of Random Sphere Packings

The macroscopic mechanical properties of colloidal particle gels strongly depend on the local arrangement of the powder particles. Experiments have shown that more heterogeneous microstructures exhibit up to one order of magnitude higher elastic properties than their more homogeneous counterparts at equal volume fraction. In this paper, packings of spherical particles are used as model structures to computationally investigate the elastic properties of coagulated particle gels as a function of their degree of heterogeneity. The discrete element model comprises a linear elastic contact law, particle bonding and damping. The simulation parameters were calibrated using a homogeneous and a heterogeneous microstructure originating from earlier Brownian dynamics simulations. A systematic study of the elastic properties as a function of the degree of heterogeneity was performed using two sets of microstructures obtained from Brownian dynamics simulation and from the void expansion method. Both sets cover a broad and to a large extent overlapping range of degrees of heterogeneity. The simulations have shown that the elastic properties as a function of the degree of heterogeneity are independent of the structure generation algorithm and that the relation between the shear modulus and the degree of heterogeneity can be well described by a power law. This suggests the presence of a critical degree of heterogeneity and, therefore, a phase transition between a phase with finite and one with zero elastic properties.Comment: 8 pages, 6 figures; Granular Matter (published online: 11. February 2012

The minimum orbital period in thermal-timescale mass transfer

We show that the usual picture of supersoft X-ray binary evolution as driven by conservative thermal-timescale mass transfer cannot explain the short orbital periods of RX J0537.7-7034 (3.5 hr) and 1E 0035.4-7230 (4.1 hr). Non-conservative evolution may produce such periods, but requires very significant mass loss, and is highly constrained.Comment: 6 pages, 5 figures; to appear in MNRA

Trends in Cancer-Center Spending on Advertising in the United States, 2005 to 2014

In the United States, cancer centers commonly advertise clinical services directly to the public. Potential benefits of such advertising include informing patients about available treatments and reducing the stigma of cancer.1, 2 Potential risks include misleading vulnerable patients and creating false hopes, increasing demand for unnecessary tests and treatments, adversely affecting existing clinician-patient relationships, and increasing healthcare costs.3, 4 Understanding trends in the advertising spending of cancer centers and the characteristics of the centers that spend the most can inform the debate about the impact of these advertisements. Our hypothesis was that advertising spending has increased and that spending is concentrated among for-profit cancer centers

Keck Spectroscopy of Faint 3<z<8 Lyman Break Galaxies:- Evidence for a Declining Fraction of Emission Line Sources In the Redshift Range 6<z<8

Using deep Keck spectroscopy of Lyman break galaxies selected from infrared imaging data taken with WFC3/IR onboard the Hubble Space Telescope, we present new evidence for a reversal in the redshift-dependent fraction of star forming galaxies with detectable Lyman alpha emission in the redshift range 6.3 < z < 8.8. Our earlier surveys with the DEIMOS spectrograph demonstrated a significant increase with redshift in the fraction of line emitting galaxies over the interval 4 < z < 6, particularly for intrinsically faint systems which dominate the luminosity density. Using the longer wavelength sensitivities of LRIS and NIRSPEC, we have targeted 19 Lyman break galaxies selected using recent WFC3/IR data whose photometric redshifts are in the range 6.3 < z < 8.8 and which span a wide range of intrinsic luminosities. Our spectroscopic exposures typically reach a 5-sigma sensitivity of < 50 A for the rest-frame equivalent width (EW) of Lyman alpha emission. Despite the high fraction of emitters seen only a few hundred million years later, we find only 2 convincing and 1 possible line emitter in our more distant sample. Combining with published data on a further 7 sources obtained using FORS2 on the ESO VLT, and assuming continuity in the trends found at lower redshift, we discuss the significance of this apparent reversal in the redshift-dependent Lyman alpha fraction in the context of our range in continuum luminosity. Assuming all the targeted sources are at their photometric redshift and our assumptions about the Lyman alpha EW distribution are correct, we would expect to find so few emitters in less than 1% of the realizations drawn from our lower redshift samples. Our new results provide further support for the suggestion that, at the redshifts now being probed spectroscopically, we are entering the era where the intergalactic medium is partially neutral.Comment: 8 pages, 5 figures, Accepted to ApJ 10/1/1

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

Inmunoterapia dual; Ipilimumab; NivolumabImmunoteràpia dual; Ipilimumab; NivolumabDual immunotherapy; Ipilimumab; NivolumabBackground To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. Patients and methods Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. Results With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. Conclusions With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.This work was supported by Bristol Myers Squibb (Princeton, New Jersey) (no grant number). Authors received no financial support or compensation for publication of this manuscript

Evaluation of health effects of air pollution in the Chestnut Ridge area : preliminary analysis

This project involves several tasks designed to take advantage of (1) a very extensive air pollution monitoring system that is operating ..n the Chestnut Ridge.region of Western Pennsylvania and (2) -the very well developed analytic dispersion models that have been previously fine-tuned to this particular area.. The major task in this project is to establish, through several distinct epidemiolopic approaches, health data to be used to test hypotheses about relations of air pollution exposures to morbidity and mortality rates in this region. Because the air quality monitoring network involves no expense to this contract this project affords a very cost-effective 6pportunity-for state-of-the-art techniques to be used in both costly areas of air pollution and health -effects data col1 ection. . The closely spaced network of monitors, plus the dispersion modeling capabilities,.allow for the investigation- of health impacts of. various pollutant gradients in neighboring geographic areas, thus minimizing -the confounding effects of social, ethnic, and economic factors. The pollutants that are monitored in this network include total gaseous sulfur, sulfates, total suspended particulates, NOx, NO, ozone/oxidants, and coefficient of haze. In addition to enabling the simulation of exposure profiles between monitors, the air quality2 modeling, along with extensive source and background inventories, will allow for upgrading the quality of the monitored data. as well as simulating the exposure levels for about 25 additional air pollutants. Another important goal of this project is to collect and test the many available models for associating.health effects with air pollution, to determine their predictive validity and their usefulness in the choice and siting of future energy facilities

Hamiltonian structure for dispersive and dissipative dynamical systems

We develop a Hamiltonian theory of a time dispersive and dissipative inhomogeneous medium, as described by a linear response equation respecting causality and power dissipation. The proposed Hamiltonian couples the given system to auxiliary fields, in the universal form of a so-called canonical heat bath. After integrating out the heat bath the original dissipative evolution is exactly reproduced. Furthermore, we show that the dynamics associated to a minimal Hamiltonian are essentially unique, up to a natural class of isomorphisms. Using this formalism, we obtain closed form expressions for the energy density, energy flux, momentum density, and stress tensor involving the auxiliary fields, from which we derive an approximate, ``Brillouin-type,'' formula for the time averaged energy density and stress tensor associated to an almost mono-chromatic wave.Comment: 68 pages, 1 figure; introduction revised, typos correcte

Reionization after Planck: the derived growth of the cosmic ionizing emissivity now matches the growth of the galaxy UV luminosity density

Thomson optical depth tau measurements from Planck provide new insights into the reionization of the universe. In pursuit of model-independent constraints on the properties of the ionising sources, we determine the empirical evolution of the cosmic ionizing emissivity. We use a simple two-parameter model to map out the evolution in the emissivity at z>~6 from the new Planck optical depth tau measurements, from the constraints provided by quasar absorption spectra and from the prevalence of Ly-alpha emission in z~7-8 galaxies. We find the redshift evolution in the emissivity dot{N}_{ion}(z) required by the observations to be d(log Nion)/dz=-0.15(-0.11)(+0.08), largely independent of the assumed clumping factor C_{HII} and entirely independent of the nature of the ionising sources. The trend in dot{N}_{ion}(z) is well-matched by the evolution of the galaxy UV-luminosity density (dlog_{10} rho_UV/dz=-0.11+/-0.04) to a magnitude limit >~-13 mag, suggesting that galaxies are the sources that drive the reionization of the universe. The role of galaxies is further strengthened by the conversion from the UV luminosity density rho_UV to dot(N)_{ion}(z) being possible for physically-plausible values of the escape fraction f_{esc}, the Lyman-continuum photon production efficiency xi_{ion}, and faint-end cut-off $M_{lim}$ to the luminosity function. Quasars/AGN appear to match neither the redshift evolution nor normalization of the ionizing emissivity. Based on the inferred evolution in the ionizing emissivity, we estimate that the z~10 UV-luminosity density is 8(-4)(+15)x lower than at $z~6, consistent with the observations. The present approach of contrasting the inferred evolution of the ionizing emissivity with that of the galaxy UV luminosity density adds to the growing observational evidence that faint, star-forming galaxies drive the reionization of the universe.Comment: 20 pages, 12 figures, 5 tables, Astrophysical Journal, updated to match version in press, Figure 6 shows the main result of the pape

Distribution of particulate matter and tissue remodeling in the human lung.

We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H(2)O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter