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During the last fifteen years there has been a paradigm shift in the continuum modelling of granular materials; most notably with the development of rheological models, such as the $\mu (I)$-rheology (where $\mu$ is the friction and I is the inertial number), but also with significant advances in theories for particle segregation. This paper details theoretical and numerical frameworks (based on OpenFOAM) which unify these currently disconnected endeavours. Coupling the segregation with the flow, and vice versa, is not only vital for a complete theory of granular materials, but is also beneficial for developing numerical methods to handle evolving free surfaces. This general approach is based on the partially regularized incompressible $\mu (I)$-rheology, which is coupled to the gravity-driven segregation theory of Gray & Ancey (J. Fluid Mech., vol. 678, 2011, pp. 353–588). These advection–diffusion–segregation equations describe the evolving concentrations of the constituents, which then couple back to the variable viscosity in the incompressible Navier–Stokes equations. A novel feature of this approach is that any number of differently sized phases may be included, which may have disparate frictional properties. Further inclusion of an excess air phase, which segregates away from the granular material, then allows the complex evolution of the free surface to be captured simultaneously. Three primary coupling mechanisms are identified: (i) advection of the particle concentrations by the bulk velocity, (ii) feedback of the particle-size and/or frictional properties on the bulk flow field and (iii) influence of the shear rate, pressure, gravity, particle size and particle-size ratio on the locally evolving segregation and diffusion rates. The numerical method is extensively tested in one-way coupled computations, before the fully coupled model is compared with the discrete element method simulations of Tripathi & Khakhar (Phys. Fluids, vol. 23, 2011, 113302) and used to compute the petal-like segregation pattern that spontaneously develops in a square rotating drum.
Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.
A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.
Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).
Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile.
Study the effect of changing testing strategies on C. difficile detection and strain diversity.
A Veterans’ Affairs hospital.
Initially, toxin EIA testing was replaced by an MST approach utilizing a glutamate dehydrogenase (GDH) and toxin EIA followed by tcdB NAAT for discordant results. After 18 months, MST was replaced by a NAAT-only strategy. Available patient stool specimens were cultured for C. difficile. Restriction endonuclease analysis (REA) strain typing and quantitative in vitro toxin testing were performed on recovered isolates.
Before MST (toxin EIA), 79 of 708 specimens (11%) were positive, and after MST (MST-A), 121 of 517 specimens (23%) were positive (P < .0001). Prior to NAAT-only testing (MST-B), 80 of the 490 specimens (16%) were positive by MST, and after NAAT-only testing was implemented, 67 of the 368 specimens (18%) were positive (P = nonsignificant). After replacing toxin EIA testing, REA strain group diversity increased (8, 13, 13, and 10 REA groups in the toxin EIA, MST-A, MST-B, and NAAT-only periods, respectively) and in vitro toxin concentration decreased. The average log10 toxin concentration of the isolates were 2.08, 1.88, 1.20 and 1.55 ng/mL for the same periods, respectively.
MST and NAAT had similar detection rates for C. difficile. Compared to toxin testing alone, they detected increased diversity of C. difficile strains, many of which were low toxin producing.
In a European, phase 3 study (SPD489-325), lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) were more effective than placebo in improving core symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
Objectives and aims
To compare post hoc the efficacy of LDX and OROS-MPH in study SPD489-325.
This 7-week, randomized, double-blind, parallel-group, dose-optimized, placebo-controlled trial enrolled patients aged 6-17 years with ADHD of at least moderate severity. Patients were randomized (1:1:1) to receive a once-daily dose of LDX (30, 50, 70 mg/day), OROS-MPH (18, 36, 54 mg/day) or placebo. Efficacy was assessed using the ADHD Rating Scale version IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Endpoint was defined as the last ontherapy treatment visit with a valid assessment.
The full analysis set comprised 317 patients (LDX, n=104; placebo, n=106; OROS-MPH, n=107). The difference between LDX and OROS-MPH in least squares mean change (95% confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of LDX (-5.6 [-8.4, -2.7]; p < 0.001; effect size, 0.541). The difference (LDX minus OROS-MPH) in the percentage of patients (95% CI) with an improved CGI-I score at endpoint was also statistically significant in favour of LDX (17.4 [5.0, 29.8]; p < 0.05).
This post hoc analysis indicated that LDX is significantly more effective than OROS-MPH in improving core symptoms and global functioning in children and adolescents with ADHD.
In a European, phase 3 study (SPD489-325), lisdexamfetamine dimesylate (LDX) was more effective than placebo in improving symptoms and global functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
Objectives and aims
To evaluate the impact of age, sex and baseline disease severity on efficacy outcomes in SPD489- 325.
This 7-week, double-blind, parallel-group, dose-optimized study enrolled patients aged 6-17 years with ADHD. Patients were randomized (1:1:1) to once-daily LDX (30, 50 or 70mg/day), osmotic-release oral system methylphenidate (OROS-MPH; 18, 36 or 54mg/day) or placebo. Efficacy outcomes were analysed in patients dichotomized by age (6-12 years [n=229] or 13-17 years [n=88]), sex (male [n=255] or female [n=62]) and baseline ADHD Rating Scale version IV (ADHD-RSIV) total score (28-41 [n=161] or 42-54 [n=152]). Endpoint was the last on-treatment visit with a valid assessment.
At endpoint, differences (active-placebo) in least-squares mean changes from baseline in ADHD-RS-IV total scores were statistically significant in all age, sex and ADHD-RS-IV total score subgroups for LDX (p< 0.001; effect sizes, 1.68-2.26) and OROS-MPH (p< 0.01; effect sizes, 0.88-1.46). Proportions of patients with a Clinical Global Impressions-Improvement rating of 1 (very much improved) or 2 (much improved) were statistically significantly greater than placebo at endpoint in all subgroups receiving LDX (p< 0.01) and in all subgroups except females receiving OROS-MPH (p< 0.05).
LDX showed greater efficacy than placebo in children and adolescents with ADHD, regardless of their age, sex or baseline disease severity.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Dense granular flows can spontaneously self-channelise by forming a pair of parallel-sided static levees on either side of a central flowing channel. This process prevents lateral spreading and maintains the flow thickness, and hence mobility, enabling the grains to run out considerably further than a spreading flow on shallow slopes. Since levees commonly form in hazardous geophysical mass flows, such as snow avalanches, debris flows, lahars and pyroclastic flows, this has important implications for risk management in mountainous and volcanic regions. In this paper an avalanche model that incorporates frictional hysteresis, as well as depth-averaged viscous terms derived from the
-rheology, is used to quantitatively model self-channelisation and levee formation. The viscous terms are crucial for determining a smoothly varying steady-state velocity profile across the flowing channel, which has the important property that it does not exert any shear stresses at the levee–channel interfaces. For a fixed mass flux, the resulting boundary value problem for the velocity profile also uniquely determines the width and height of the channel, and the predictions are in very good agreement with existing experimental data for both spherical and angular particles. It is also shown that in the absence of viscous (second-order gradient) terms, the problem degenerates, to produce plug flow in the channel with two frictionless contact discontinuities at the levee–channel margins. Such solutions are not observed in experiments. Moreover, the steady-state inviscid problem lacks a thickness or width selection mechanism and consequently there is no unique solution. The viscous theory is therefore a significant step forward. Fully time-dependent numerical simulations to the viscous model are able to quantitatively capture the process in which the flow self-channelises and show how the levees are initially emplaced behind the flow head. Both experiments and numerical simulations show that the height and width of the channel are not necessarily fixed by these initial values, but respond to changes in the supplied mass flux, allowing narrowing and widening of the channel long after the initial front has passed by. In addition, below a critical mass flux the steady-state solutions become unstable and time-dependent numerical simulations are able to capture the transition to periodic erosion–deposition waves observed in experiments.
Shallow granular avalanches on slopes close to repose exhibit hysteretic behaviour. For instance, when a steady-uniform granular flow is brought to rest it leaves a deposit of thickness
on a rough slope inclined at an angle
to the horizontal. However, this layer will not spontaneously start to flow again until it is inclined to a higher angle
, or the thickness is increased to
. This simple phenomenology leads to a rich variety of flows with co-existing regions of solid-like and fluid-like granular behaviour that evolve in space and time. In particular, frictional hysteresis is directly responsible for the spontaneous formation of self-channelized flows with static levees, retrogressive failures as well as erosion–deposition waves that travel through the material. This paper is motivated by the experimental observation that a travelling-wave develops, when a steady uniform flow of carborundum particles on a bed of larger glass beads, runs out to leave a deposit that is approximately equal to
. Numerical simulations using the friction law originally proposed by Edwards et al. (J. Fluid Mech., vol. 823, 2017, pp. 278–315) and modified here, demonstrate that there are in fact two travelling waves. One that marks the trailing edge of the steady-uniform flow and another that rapidly deposits the particles, directly connecting the point of minimum dynamic friction (at thickness
) with the deposited layer. The first wave moves slightly faster than the second wave, and so there is a slowly expanding region between them in which the flow thins and the particles slow down. An exact inviscid solution for the second travelling wave is derived and it is shown that for a steady-uniform flow of thickness
it produces a deposit close to
for all inclination angles. Numerical simulations show that the two-wave structure deposits layers that are approximately equal to
for all initial thicknesses. This insensitivity to the initial conditions implies that
is a universal quantity, at least for carborundum particles on a bed of larger glass beads. Numerical simulations are therefore able to capture the complete experimental staircase procedure, which is commonly used to determine the
curves by progressively increasing the inclination of the chute. In general, however, the deposit thickness may depend on the depth of the flowing layer that generated it, so the most robust way to determine
is to measure the deposit thickness from a flow that was moving at the minimum steady-uniform velocity. Finally, some of the pathologies in earlier non-monotonic friction laws are discussed and it is explicitly shown that with these models either steadily travelling deposition waves do not form or they do not leave the correct deposit depth
In 2008, for the first time in the history of this country, a black woman became First Lady of the United States. During Barack Obama's presidency, Michelle Obama was ever present in the public eye for her advocacy on issues related to health, military families, education, and for promoting the interests of women and girls. This article contributes to ongoing scholarly discourse, as well as extensive media coverage and analysis, regarding Obama's role as wife and first lady by critically examining how the particular model of motherhood she embraced and exhibited, a model firmly rooted in the black American community, was designed to challenge negative stereotypes of black women, maternity, and families. We address the following questions in this work: How did Obama's identity as a black woman influence the policies she championed as first lady? Does Obama's mothering relate to stereotypes of black mothers and help (re)define black motherhood, and if so, how? What does it mean to be a black mater gentis or mother of the nation? Drawing on her speeches and policy initiatives, we reveal how Michelle Obama defied dominant and oppressive stereotypes of black women and mothers while simultaneously (re)defining black womanhood and motherhood for the nation.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
When a layer of static grains on a sufficiently steep slope is disturbed, an upslope-propagating erosion wave, or retrogressive failure, may form that separates the initially static material from a downslope region of flowing grains. This paper shows that a relatively simple depth-averaged avalanche model with frictional hysteresis is sufficient to capture a planar retrogressive failure that is independent of the cross-slope coordinate. The hysteresis is modelled with a non-monotonic effective basal friction law that has static, intermediate (velocity decreasing) and dynamic (velocity increasing) regimes. Both experiments and time-dependent numerical simulations show that steadily travelling retrogressive waves rapidly form in this system and a travelling wave ansatz is therefore used to derive a one-dimensional depth-averaged exact solution. The speed of the wave is determined by a critical point in the ordinary differential equation for the thickness. The critical point lies in the intermediate frictional regime, at the point where the friction exactly balances the downslope component of gravity. The retrogressive wave is therefore a sensitive test of the functional form of the friction law in this regime, where steady uniform flows are unstable and so cannot be used to determine the friction law directly. Upper and lower bounds for the existence of retrogressive waves in terms of the initial layer depth and the slope inclination are found and shown to be in good agreement with the experimentally determined phase diagram. For the friction law proposed by Edwards et al. (J. Fluid. Mech., vol. 823, 2017, pp. 278–315, J. Fluid. Mech., 2019, (submitted)) the magnitude of the wave speed is slightly under-predicted, but, for a given initial layer thickness, the exact solution accurately predicts an increase in the wave speed with higher inclinations. The model also captures the finite wave speed at the onset of retrogressive failure observed in experiments.
In response to concerns about acetolactate synthase (ALS) inhibitor–resistant weeds in wheat production systems, we explored the efficacy of managing Bromus spp., downy and Japanese bromes, in a winter wheat system using alternative herbicide treatments applied in either fall or spring. Trials were established at Lethbridge and Kipp, Alberta, and Scott, Saskatchewan, Canada over three growing seasons (2012–2014) to compare the efficacy of pyroxasulfone (a soil-applied very-long-chain fatty acid elongase inhibitor; WSSA Group 15) and flumioxazin (a protoporphyrinogen oxidase inhibitor; WSSA Group 14) against industry-standard ALS-inhibiting herbicides for downy and Japanese brome control. Winter wheat injury from herbicide application was minor, with the exception of flucarbazone application at Scott. Bromus spp. control was greatest with pyroxsulam and all herbicide treatments containing pyroxasulfone. Downy and Japanese bromes were controlled least by thiencarbazone and flumioxazin, respectively, whereas Bromus spp. had intermediate responses to the other herbicides tested. Herbicides applied in fall resulted in reduced winter wheat yield relative to the spring applications. Overall, pyroxasulfone or pyroxsulam provided the most efficacious Bromus spp. control compared with the other herbicides and consistently maintained optimal winter wheat yields. Therefore, pyroxasulfone could facilitate management of Bromus spp. resistant to ALS inhibitors in winter wheat in the southern growing regions of western Canada. Improved weed control and delayed herbicide resistance may be achieved when pyroxasulfone is applied in combination with flumioxazin.
The goal of this study was to perform in situ electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in peripheral nerves to create a soft, precisely located injectable conductive polymer electrode for bi-directional communication. Intraneural PEDOT polymerization was performed to target both outer and inner fascicles via custom fabricated 3D printed cuff electrodes and monomer injection strategies using a combination electrode-cannula system. Electrochemistry, histology, and laser light sheet microscopy revealed the presence of PEDOT at specified locations inside of peripheral nerve. This work demonstrates the potential for using in situ PEDOT electrodeposition as an injectable electrode for recording and stimulation of peripheral nerves.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.
For this study, we adapted the Montgomery Borgatta Caregiver Burden Scale, used widely in the United States, to the Saudi Arabian context. To produce an Arabic, culturally sensitive version of the scale, we conducted semi-structured interviews with 20 Saudi family caregivers. The Arabic version of the scale was tested, and participants were asked to comment on the appropriateness of items for the construct of “caregiver burden” using the repertory grid technique and laddering procedure – two constructivist methods derived from personal construct theory. From interview findings, we examined the content of the items and the caregiver burden construct itself. Our findings suggest that the use of constructivist methods to refine constructs and quantitative instruments is highly informative. This strategy is feasible even when little is known about the investigated constructs in the target culture and further elucidates our understanding of cross-cultural variations or invariance of different versions of the scale.
We assessed various locations and frequency of environmental sampling to maximize information and maintain efficiency when sampling for Acinetobacter baumannii. Although sampling sites in closer proximity to the patient were more likely positive, to fully capture environmental contamination, we found value in sampling all sites and across multiple days.