Intermittency and local Reynolds number in Navier-Stokes turbulence: A cross-over scale in the Caffarelli-Kohn-Nirenberg integral

We study space-time integrals, which appear in the Caffarelli-Kohn-Nirenberg (CKN) theory for the Navier-Stokes equations analytically and numerically. The key quantity is written in standard notations δ(r)=1/(νr)∫Qr(∇,u)2dxdtδ(r)=1/(νr)∫Qr∇u2dxdt, which can be regarded as a local Reynolds number over a parabolic cylinder Q r . First, by re-examining the CKN integral, we identify a cross-over scale r∗∝L(∥∇u∥2L2¯¯¯¯¯¯¯¯¯¯¯¯∥∇u∥2L∞)1/3,r*∝L‖∇u‖L22¯‖∇u‖L∞21/3, at which the CKN Reynolds number δ(r) changes its scaling behavior. This reproduces a result on the minimum scale r min in turbulence:r2min∥∇u∥∞∝ν,rmin2‖∇u‖∞∝ν, consistent with a result of Henshaw et al. [“On the smallest scale for the incompressible Navier-Stokes equations,” Theor. Comput. Fluid Dyn.1, 65 (1989)10.1007/BF00272138]. For the energy spectrum E(k) ∝ k −q   (1 < q < 3), we show that r * ∝ ν a with a=43(3−q)−1a=43(3−q)−1. Parametric representations are then obtained as ∥∇u∥∞∝ν−(1+3a)/2‖∇u‖∞∝ν−(1+3a)/2 and r min ∝ ν3(a+1)/4. By the assumptions of the regularity and finite energy dissipation rate in the inviscid limit, we derive limp→∞ζpp=1−ζ2limp→∞ζpp=1−ζ2 for any phenomenological models on intermittency, where ζ p is the exponent of pth order (longitudinal) velocity structure function. It follows that ζ p ⩽ (1 − ζ2)(p − 3) + 1 for any p ⩾ 3 without invoking fractal energy cascade. Second, we determine the scaling behavior of δ(r) in direct numerical simulations of the Navier-Stokes equations. In isotropic turbulence around R λ ≈ 100 starting from random initial conditions, we have found that δ(r) ∝ r 4 throughout the inertial range. This can be explained by the smallness of a ≈ 0.26,with a result that r * is in the energy-containing range. If the β-model is perfectly correct, the intermittency parameter a must be related to the dissipation correlation exponent μ as μ=4a1+a≈0.8,μ=4a1+a≈0.8, which is larger than the observed μ ≈ 0.20. Furthermore, corresponding integrals are studied using the Burgers vortex and the Burgers equation. In those single-scale phenomena, the cross-over scale lies in the dissipative range.The scale r * offers a practical method of quantifying intermittency. This paper also sorts out a number of existing mathematical bounds and phenomenological models on the basis of the CKN Reynolds number

Lived experiences of South African rehabilitation practitioners during coronavirus disease 2019

Background: In South Africa, the sharp rise in people with severe illness because of coronavirus disease 2019 (COVID-19) in early 2020, meant that health systems needed to adapt services and operations, including rehabilitation services. Important insights into the lived experiences of rehabilitation personnel enacting these adaptations in an African context are limited. Objectives: The aim of this study was to explore the lived experiences of rehabilitation practitioners working in the public sector in South Africa during the COVID-19 pandemic. Method: A phenomenological approach and a duo-ethnographic design were used. A recruitment letter was circulated requesting volunteers. Maximum variation sampling was used to select the 12 participants of this study. Data were collected through interviews via Zoom, and critical conversations were facilitated by a non-rehabilitation partner who is known for challenging health inequities. The interviews were audio-recorded and transcribed verbatim. Data were analysed through elements of qualitative content and thematic analysis. Data were coded, categorised, clustered into concepts and formulated into themes. Results: Three themes were identified: (1) ‘Management became the enemy’, (2) ‘Tired of being resilient’ and (3) ‘Think out of the box…think on our feet’. Conclusion: The results of this study highlighted new ways of practice, innovative adaptations, and usage of resources and platforms. Contribution: This study highlights the re-imagining of accessible rehabilitation services that could lead to deeper onto-epistemological shifts amongst the rehabilitation practitioners

Civil society leadership in the struggle for AIDS treatment in South Africa and Uganda

Includes abstract.Includes bibliographical references.This thesis is an attempt to theorise and operationalise empirically the notion of ‘civil society leadership’ in Sub-Saharan Africa. ‘AIDS leadership,’ which is associated with the intergovernmental institutions charged with coordinating the global response to HIV/AIDS, is both under-theorised and highly context-specific. In this study I therefore opt for an inclusive framework that draws on a range of approaches, including the literature on ‘leadership’, institutions, social movements and the ‘network’ perspective on civil society mobilisation. This framework is employed in rich and detailed empirical descriptions (‘thick description’) of civil society mobilisation around AIDS, including contentious AIDS activism, in the key case studies of South Africa and Uganda. South Africa and Uganda are widely considered key examples of poor and good leadership (from national political leaders) respectively, while the Treatment Action Campaign (TAC) and The AIDS Support Organisation (TASO) are both seen as highly effective civil society movements. These descriptions emphasise ‘transnational networks of influence’ in which civil society leaders participated (and at times actively constructed) in order to mobilise both symbolic and material resources aimed at exerting influence at the transnational, national and local levels

Developing a core outcome set for fistulising perianal Crohn's disease

OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback fromtheir panel(in the second round) andall participants(in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study.The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100213

From Duty to Right: The Role of Public Education in the Transition to Aging Societies

This paper argues that the introduction of compulsory schooling in early industrialization promoted the growth process that eventually led to a vicious cycle of population aging and negative pressure on education policy. In the early phases of industrialization, public education was undesirable for the young poor who relied on child labor. Compulsory schooling therefore discouraged childbirth, while the accompanying industrialization stimulated their demand for education. The subsequent rise in the share of the old population, however, limited government resources for education, placing heavier financial burdens on the young. This induced further fertility decline and population aging, and the resulting cycle may have delayed the growth of advanced economies in the last few decades