Mixing in density- and viscosity-stratified flows

The lock-exchange problem is used extensively to study the flow dynamics of density-driven flows, such as gravity currents, and as a canonical problem to mixing in stratified flows. Opposite halves of a domain are filled with two fluids of different densities and held in place by a lock-gate. Upon release, the density difference drives the flow causing the fluids to slosh back and forth. In many scenarios, density stratification will also impose a viscosity stratification (e.g., if there are suspended sediments or the two fluids are distinct). However, numerical models often neglect variable viscosity. This paper characterizes the effect of both density and viscosity stratification in the lock-exchange configuration. The governing Navier-Stokes equations are solved using direct numerical simulation. Three regimes are identified in terms of the viscosity ratio μ 2 / μ 1 = (1 + γ) between the dense and less dense fluids: when γ ≪ 1, the flow dynamics are similar to the equal-viscosity case; for intermediate values (γ ∼ 1), viscosity inhibits interface-scale mixing leading to a global reduction in mixing and enhanced transfer between potential and kinetic energy. Increasing the excess viscosity ratio further (γ ≫ 1) results in significant viscous dissipation. Although many gravity or turbidity current models assume constant viscosity, our results demonstrate that viscosity stratification can only be neglected when γ ≪ 1. The initial turbidity current composition could enhance its ability to become self-sustaining or accelerating at intermediate excess viscosity ratios. Currents with initially high excess viscosity ratio may be unable to dilute and propagate long distances because of the decreased mixing rates and increased dissipation

Pulse propagation in gravity currents

Real world gravity current flows rarely exist as a single discrete event, but are instead made up of multiple surges. This paper examines the propagation of surges as pulses in gravity currents. Using theoretical shallow-water modeling, we analyze the structure of pulsed flows created by the sequential release of two lock-boxes. The first release creates a gravity current, while the second creates a pulse that eventually propagates to the head of the first current. Two parameters determine the flow structure: the densimetric Froude number at the head of the current, Fr, and a dimensionless time between releases, tre. The shallow-water model enables the flow behavior to be mapped in (Fr, tre) space. Pulse speed depends on three critical characteristic curves: two that derive from the first release and correspond to a wavelike disturbance which reflects between the head of the current and the back of the lock-box and a third that originates from the second release and represents the region of the flow affected by the finite supply of source material. Pulses have non-negative acceleration until they intersect the third characteristic, after which they decelerate. Variations in pulse speed affect energy transfer and dissipation. Critically for lahars, landslides, and avalanches, pulsed flows may change from erosional to depositional, further affecting their dynamics. Gravity current hazard prediction models for such surge-prone flows may underpredict risk if they neglect internal flow dynamics

Preliminary development and validation of a new endof-life patient-reported outcome measure assessing the ability of patients to finalise their affairs at the end of life

Introduction:The ability of patients to finalise their affairs at the end of life is an often neglected aspect of quality of life (QOL) measurement in palliative care effectiveness research despite compelling evidence of the high value patients place on this domain. Objective: This paper describes the preliminary development and evaluation of a new, single-item, end-of-life patientreported outcome measure (EOLPRO) designed to capture changes in the ability of patients to finalise their affairs at the end of life. Methods: Cognitive interviews with purposively sampled Australian palliative care patients (N = 9) were analysed thematically to explore content validity. Simultaneously, secondary analysis of data from a randomised controlled trial comparing ketamine and placebo for the management of cancer pain (N = 185) evaluated: construct validity; test-retest reliability; and responsiveness. Results:Preliminary findings suggest patients interpret the new measure consistently. The EOLPRO captures the ability to complete physical tasks and finalise practical matters although it is unclear whether emotional tasks or resolution of relationship issues are considered. Personal and financial affairs should be separated to allow for differences in ability for these two types of affairs. The significant correlation between performance status and EOLPRO scores (r = 0.41, p,<.01, n = 137) and expected relationships between EOLPRO and proximity to death and constipation demonstrated construct validity. Pre-and post-treatment EOLPRO scores moderately agreed (n = 14, k = 0.52 [95% CI 0.19, 0.84]) supporting reliability. The measure's apparent lack of sensitivity to discriminate between treatment responders and non-responders may be confounded. Conclusion:Based on the preliminary findings, the EOLPRO should be separated into 'personal' and 'financial' affairs with further testing suggested, particularly to verify coverage and responsiveness. Initial evaluation suggests that the single-item EOLPRO is a useful addition to QOL outcome measurement in palliative care effectiveness research because common palliative care specific QOL questionnaires do not include or explicitly capture this domain. © 2014 McCaffrey et al

Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first‐line sunitinib: a medical chart review across ten centers in five European countries

Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity

A meta-study of relationships between fluvial channel-body stacking pattern and aggradation rate: implications for sequence stratigraphy

A quantitative comparison of 20 literature case studies of fluvial sedimentary successions tests common assumptions made in published models of alluvial architecture concerning (1) inverse proportionality between channel-deposit density and floodplain aggradation rates, and (2) resulting characteristics of channel-body geometries and connectedness. Our results do not support the relationships predicted by established stratigraphy models: the data suggest that channel-body density, geometry, and stacking pattern are not reliable diagnostic indicators of rates of accommodation creation. Hence, these architectural characteristics alone do not permit the definition of accommodation-based “systems tracts” and “settings”, and this calls into question current sequence stratigraphic practice in application to fluvial successions

Heterogeneous coupling of the Sumatran megathrust constrained by geodetic and paleogeodetic measurements

Geodetic and paleogeodetic measurements of interseismic strain above the Sumatran portion of the Sunda subduction zone reveal a heterogeneous pattern of coupling. Annual banding in corals provides vertical rates of deformation spanning the last half of the 20th century, and repeated GPS surveys between 1991 and 2001 and continuous measurements at GPS stations operated since 2002 provide horizontal velocities. Near the equator, the megathrust is locked over a narrow width of only a few tens of kilometers. In contrast, the locked fault zone is up to about 175 km wide in areas where great interplate earthquakes have occurred in the past. Formal inversion of the data reveals that these strongly coupled patches are roughly coincident with asperities that ruptured during these events. The correlation is most spectacular for rupture of the M_w 8.7 Nias-Simeulue earthquake of 2005, which released half of the moment deficit that had accumulated since its previous rupture in 1861, suggesting that this earthquake was overdue. Beneath the Mentawai islands, strong coupling is observed within the overlapping rupture areas of the great earthquakes of 1797 and 1833. The accumulated slip deficit since these events is slowly reaching the amount of slip that occurred during the 1833 earthquake but already exceeds the slip that occurred during the 1797 earthquake. Thus, rerupture of part of the Mentawai patch in September 2007 was not a surprise. In contrast, coupling is low below the Batu islands near the equator and around Enggano island at about 5°S, where only moderate earthquakes (M_w < 8.0) have occurred in the past two centuries. The correlation of large seismic asperities with patches that are locked during the interseismic period suggests that they are persistent features. This interpretation is reinforced by the fact that the large locked patches and great ruptures occur beneath persistent geomorphologic features, the largest outer arc islands. Depth- and convergence-rate-dependent temperature might influence the pattern of coupling, through its effect on the rheology of the plate interface, but other influences are required to account for the observed along-strike heterogeneity of coupling. In particular, subduction of the Investigator Fracture Zone could be the cause for the low coupling near the equator

The effect of pre-shot routines on golf wedge shot performance

The objective of this study was to examine the effect of pre-performance routines among golfers of low skill and non-golfers on wedge golf shot performance. The intervention strategies involved a physical skill and cognitive-behavioral routine program, as well as a physical skills-only program. Performance was measured on a pre-intervention test, postintervention test, and following a period of time without treatment, and involved wedge shots being played from distances of 40, 50, and 60 m from a target. Participants in this study (N = 68) were assigned to either a golfer or non-golfer group. Participants in the treatment groups attended 2 practice sessions per week during the acquisition phase. A variable practice design was incorporated during the intervention phase. Non-golfers in both intervention groups improved performance following the acquisition phase and maintained these levels of performance in the retention test. Greater improvements in performance were found in the non-golfer physical skills and cognitive-behavioral routine group. The non-golfer physical skills and cognitive-behavioral routine group was the only group to realize significant improvements in performance when comparing initial test performance measures to post-intervention and retention test performance measures across all test distances. Although the golfer treatment groups had consistent improvement in performance measures following the intervention phase, these improvements did not reach statistical significance in the majority of cases

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants