Addictions, Social Deprivation and Cessation Failure in Head and Neck Squamous Cell Carcinoma Survivors.

AIM: To evaluate the evolution of addictions (tobacco and alcohol) and social precarity in head and neck squamous cell carcinoma survivors when these factors are addressed from the time of diagnosis. METHODS: Addictions and social precarity in patients with a new diagnosis of HNSCC were assessed through the EPICES score, the Fagerström score, and the CAGE questionnaire. When identified as precarious/dependent, patients were referred to relevant addiction/social services. RESULTS: One hundred and eighty-two patients were included. At the time of diagnosis, an active tobacco consumption was associated with alcohol drinking (Fisher's exact test, p < 0.001). Active smokers were more socially deprived (mean EPICES score = mES = 36.2 [±22.1]) than former smokers (mES = 22.8 [±17.8]) and never smokers (mES = 18.9 [±14.5]; Kruskal-Wallis, p < 0.001). The EPICES score was correlated to the Fagerström score (Kruskal-Wallis, p < 0.001). Active drinkers (mES = 34.1 [±21.9]) and former drinkers (mES = 32.7 [±21]) were more likely to be socially deprived than those who never drank (mES = 20.8 [±17.1]; Krukal-Wallis, p < 0.001). A Fagerström score improvement at one year was associated to a CAGE score improvement (Fisher's exact test, p < 0.001). Tobacco and alcohol consumption were more than halved one year after treatment. Patients who continued to smoke one year after diagnosis were significantly more likely to continue to drink (Fisher's exact test, p < 0.001) and had a significantly higher initial EPICES score (Kruskal-Wallis, p < 0.001). CONCLUSIONS: At one year, addictions and social deprivation tend to improve when taken care of from the diagnosis. The most dependent patients and those with multiple frailties are at highest risk of cessation failure.

Mechanisms for recirculation cells in granular flows in rotating cylindrical rough tumblers.

Friction at the endwalls of partially filled horizontal rotating tumblers induces curvature and axial drift of particle trajectories in the surface flowing layer. Here we describe the results of a detailed discrete element method study of the dry granular flow of monodisperse particles in three-dimensional cylindrical tumblers with endwalls and cylindrical wall that can be either smooth or rough. Endwall roughness induces more curved particle trajectories, while a smooth cylindrical wall enhances drift near the endwall. This drift induces recirculation cells near the endwall. The use of mixed roughness (cylindrical wall and endwalls having different roughness) shows the influence of each wall on the drift and curvature of particle trajectories as well as the modification of the free surface topography. The effects act in opposite directions and have variable magnitude along the length of the tumbler such that their sum determines both direction of net drift and the recirculation cells. Near the endwalls, the dominant effect is always the endwall effect, and the axial drift for surface particles is toward the endwalls. For long enough tumblers, a counter-rotating cell occurs adjacent to each of the endwall cells having a surface drift toward the center because the cylindrical wall effect is dominant there. These cells are not dynamically coupled with the two endwall cells. The competition between the drifts induced by the endwalls and the cylindrical wall determines the width and drift amplitude for both types of cells.

Self-Induced Rayleigh-Taylor Instability in Segregating Dry Granular Flows.

Dry-granular material flowing on rough inclines can experience a self-induced Rayleigh-Taylor (RT) instability followed by the spontaneous emergence of convection cells. For this to happen, particles are different in size and density; the larger particles are denser but still segregate toward the surface. When the flow is initially made of two layers of particles (dense particles above), a RT instability develops during the flow. When the flow is initially made of one homogeneous layer mixture, the granular segregation leads to the formation of an unstable layer of large, dense particles at the surface, that subsequently destabilizes in a RT plume pattern. The unstable density gradient has been only induced by the motion of the granular matter. This self-induced Rayleigh-Taylor instability and the two-layer RT instability are studied using two different methods: experiments and simulations. At last, contrary to the usual fluid behavior where the RT instability relaxes into two superimposed stable layers of fluid, the granular flow evolves to a pattern of alternated bands corresponding to recirculation cells analogous to Rayleigh-Bénard convection cells where segregation sustains the convective motion.

Recirculation cells for granular flow in cylindrical rotating tumblers.

To better understand the velocity field and flowing layer structure, we have performed a detailed discrete element method study of the flow of monodisperse particles in a partially filled three-dimensional cylindrical rotating tumblers. Similar to what occurs near the poles in spherical and conical tumblers, recirculation cells (secondary flows) develop near the flat endwalls of a cylindrical tumbler in which particles near the surface drift axially toward the endwall, while particles deeper in the flowing layer drift axially toward the midlength of the tumbler. Another recirculation cell with the opposite sense develops next to each endwall recirculation cell, extending to the midlength of the tumbler. For a long enough tumbler, each endwall cell is about one quarter of the tumbler diameter in length. Endwall cells are insensitive to tumbler length and relatively insensitive to rotation speed (so long as the flowing layer remains flat and continuously flowing) or fill level (from 25% to 50% full). However, for shorter tumblers (0.5 to 1.0 length/diameter aspect ratio) the endwall cell size does not change much, while center cells reduce their size and eventually disappear for the shortest tumblers. For longer tumblers (length/diameter aspect ratio larger than 2), a stagnation zone appears in between the central cells. These results provide insight into the mixing of monodisperse particles in rotating cylindrical tumblers as well as the frictional effects of the tumbler endwalls.

Evidence of reverse and intermediate size segregation in dry granular flows down a rough incline.

In a dry granular flow, size segregation had been shown to behave differently for a mixture containing a few large particles with a size ratio above 5 [N. Thomas, Phys. Rev. E 62, 961 (2000)1063-651X10.1103/PhysRevE.62.961]. For moderately large size ratios, large particles migrate to an intermediate depth in the bed: this is called "intermediate segregation." For the largest size ratios, large particles migrate down to the bottom of the flow: this is called "reverse segregation," in contrast with surface segregation. As the reversal and intermediate depth values depend on the fraction of particles, this numerical study mainly uses one single large tracer. Small fractions of large beads are also computed showing the link between single tracer behavior and collective segregation process. For each device (half-filled rotating tumbler and rough plane), two (2D) and three (3D) dimensional cases are distinguished. In the tumbler, the trajectories of a large tracer show that it reaches a constant depth during the flowing phase. For large size ratios, this depth is intermediate. A progressive sinking of the depth is obtained when the size ratio is increased. The largest size ratios correspond to tracers being at the bottom of the flowing layer. All 3D simulation results are in quantitative agreement with the experimental surface, intermediate, and reverse-segregation results. In the flow down a rough incline, a large tracer reaches an equilibrium depth during flow. For large size ratios, the depth is inside the bed, at an intermediate position, and for the largest size ratios, this depth is reverse, located near the bottom. Results are slightly different for a thin or a thick flow. For 3D thick flows, the reversal between surface and bottom positions occurs within a short range of size ratios: no tracer stabilizes near half-height and two reachable intermediate depth layers exist, below the surface and above the bottom reverse layer. For 3D thin flows, all intermediate depths are reachable by a tracer, depending on the size ratio. The numerical study of larger fractions of tracers (5% or 10%) shows the three segregation patterns (surface, intermediate, reverse) corresponding to the three types of equilibrium depth. The reversal is smoother than for a single tracer, and happens around the size ratio 4.5, in good agreement with experiments.

Influence of rough and smooth walls on macroscale granular segregation patterns.

Size bidisperse granular materials in a spherical tumbler segregate into two different patterns of three bands with either small particles at the equator and large particles at the poles or vice versa, depending upon the fill level in the tumbler. Here we use discrete element method simulations with supporting qualitative experiments to explore the effect of the tumbler wall roughness on the segregation pattern, modeling the tumbler walls as either a closely packed monolayer of fixed particles resulting in a rough wall or a frictional geometrically smooth wall. Even though the tumbler wall is in contact with the flowing layer only at its periphery, the impact of wall roughness is profound. Smooth walls tend toward a small-large-small (SLS) band pattern at the pole-equator-pole at all but the highest fill fractions; rough walls tend toward a large-small-large (LSL) band pattern at all but the lowest fill fractions. This comes about because smooth walls induce poleward axial drift of small particles and an equator-directed drift for large particles, resulting in an SLS band pattern. On the other hand, rough walls result in both sizes of particles moving poleward at the surface of the flow. Due to radial segregation, small particles percolate lower in the flowing layer and when arriving near the pole are caught in the return current drift that carries them back toward the equator incrementally with each passage through the flowing layer, while large particles remain at the surface near the pole, resulting in an LSL band pattern. The tendency toward either of the two segregation patterns depends on the fill level in the tumbler and the roughness of the tumbler's bounding wall.

Influence of rough and smooth walls on macroscale flows in tumblers.

Walls in discrete element method simulations of granular flows are sometimes modeled as a closely packed monolayer of fixed particles, resulting in a rough wall rather than a geometrically smooth wall. An implicit assumption is that the resulting rough wall differs from a smooth wall only locally at the particle scale. Here we test this assumption by considering the impact of the wall roughness at the periphery of the flowing layer on the flow of monodisperse particles in a rotating spherical tumbler. We find that varying the wall roughness significantly alters average particle trajectories even far from the wall. Rough walls induce greater poleward axial drift of particles near the flowing layer surface but decrease the curvature of the trajectories. Increasing the volume fill level in the tumbler has little effect on the axial drift for rough walls but increases the drift while reducing curvature of the particle trajectories for smooth walls. The mechanism for these effects is related to the degree of local slip at the bounding wall, which alters the flowing layer thickness near the walls, affecting the particle trajectories even far from the walls near the equator of the tumbler. Thus, the proper choice of wall conditions is important in the accurate simulation of granular flows, even far from the bounding wall.

Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase.

Prostaglandin (PG)E2 is a potent mediator of pain and inflammation, and high levels of this lipid mediator are observed in numerous disease states. The inhibition of PGE2 production to control pain and to treat diseases such as rheumatoid arthritis to date has depended on nonsteroidal antiinflammatory agents such as aspirin. However, these agents inhibit the synthesis of all prostanoids. To produce biologically active PGE2, PGE synthases catalyze the isomerization of PGH2 into PGE2. Recently, several PGE synthases have been identified and cloned, but their role in inflammation is not clear. To study the physiological role of the individual PGE synthases, we have generated by targeted homologous recombination a mouse line deficient in microsomal PGE synthase 1 (mPGES1) on the inbred DBA/1lacJ background. mPGES1-deficient (mPGES1-/-) mice are viable and fertile and develop normally compared with wild-type controls. However, mPGES1-/- mice displayed a marked reduction in inflammatory responses compared with mPGES1+/+ mice in multiple assays. Here, we identify mPGES1 as the PGE synthase that contributes to the pathogenesis of collagen-induced arthritis, a disease model of human rheumatoid arthritis. We also show that mPGES1 is responsible for the production of PGE2 that mediates acute pain during an inflammatory response. These findings suggest that mPGES1 provides a target for the treatment of inflammatory diseases and pain associated with inflammatory states.