Simulation of throttle flow with two phase and single phase homogenous equilibrium model

This paper aims to compare the results of two commonly used methods for the simulation of cavitating flows; one is the two phase mass transfer approach and the other is a homogenous equilibrium model. Both methodologies are compared in a shock tube and a throttle flow, which resembles the constrictions in Diesel injector passages. The mass transfer rate in the two phase model plays the fundamental role in affecting how close to equilibrium the model is; by increasing the mass transfer the two phase model comes close to the homogenous equilibrium model

Crackling Noise, Power Spectra and Disorder Induced Critical Scaling

Crackling noise is observed in many disordered non-equilibrium systems in response to slowly changing external conditions. Examples range from Barkhausen noise in magnets to acoustic emission in martensites to earthquakes. Using the non-equilibrium random field Ising model, we derive universal scaling predictions for the dependence of the associated power spectra on the disorder and field sweep rate, near an underlying disorder-induced non-equilibrium critical point. Our theory applies to certain systems in which the crackling noise results from avalanche-like response to a (slowly) increasing external driving force, and is characterized by a broad power law scaling regime of the power spectra. We compute the critical exponents and discuss the relevance of the results to experiments.Comment: 27 Latex Pages, 14 eps figure

Local mean-field study of capillary condensation in silica aerogels

We apply local mean-field (i.e. density functional) theory to a lattice model of a fluid in contact with a dilute, disordered gel network. The gel structure is described by a diffusion-limited cluster aggregation model. We focus on the influence of porosity on both the hysteretic and the equilibrium behavior of the fluid as one varies the chemical potential at low temperature. We show that the shape of the hysteresis loop changes from smooth to rectangular as the porosity increases and that this change is associated to disorder-induced out-of-equilibrium phase transitions that differ on adsorption and on desorption. Our results provide insight in the behavior of $^4$He in silica aerogels.Comment: 19 figure

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease:Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (&lt;45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.</p

Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria

Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (60 mL/min/1.73 m2) and UACR (300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR 300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791

PARE0009 COMMUNITY ADVISORY BOARD INPUT CAN MAKE LAY SUMMARIES OF CLINICAL TRIAL RESULTS MORE UNDERSTANDABLE

Background:Under European Union (EU) Clinical Trial regulations,1clinical research sponsors (CRSs) must ensure all studies performed in the EU are accompanied by a trial summary for laypersons, published within 1 year of study completion. These lay summaries should disseminate clinical trial results in an easy-to-understand way for trial participants, patient and caregiver communities, and the general public. The European Patients Forum (EPF)2and European Patients' Academy on Therapeutic Innovation (EUPATI)3encourage CRSs to engage with patient organisations (POs) in the development of lay summaries. This recognises the patients' contribution to clinical research and supports the development of patient-focused material.Objectives:We share learnings from a collaboration between scleroderma POs and a CRS to create the SENSCIS® trial (NCT02597933) written and video lay summaries.Methods:A community advisory board (CAB), comprising representatives from 11 scleroderma POs covering a range of countries/regions, was formed based on the EURORDIS charter for collaboration in clinical research.4Through three structured meetings, over a seven-month period, the CAB provided advice on lay summary materials (written and video) drafted by the CRS' Lay Summary Group (Fig. 1). At each review cycle, the CAB advice was addressed to make content more understandable and more relevant for patients and the general public.Results:The CAB advised that the existence of lay summaries is not well known in the patient community and also recommended the development of trial-specific lay summary videos to further improve understandability of the clinical trial results for the general public. Videos are a key channel of communication, enabling access to information for people with specific health needs and lower literacy levels. Following CAB advice, the CRS developed a stand-alone video entitled"What are lay summaries?"and a trial-specific lay summary video. Revisions to lay summary content (written and video) included colour schemes, iconography and language changes to make content more understandable. For videos, adjustments to animation speed, script and voiceover were implemented to improve clarity and flow of information (Fig. 2). Approved final versions of lay summary materials are publicly available on the CRS website. Translation into languages representing trial-site countries is in progress to widen access to non-English speakers and, where possible, local versions are being reviewed by the patient community.Conclusion:Structured collection and implementation of CAB advice can make lay summary materials more understandable for the patient community and wider general public.References:[1]EU. Summaries of clinical trial results for laypersons. 2018[2]EPF. EPF position: clinical trial results – communication of the lay summary. 2015[3]EUPATI. Guidance for patient involvement in ethical review of clinical trials. 2018[4]EURORDIS. Charter for Collaboration in Clinical Research in Rare Diseases. 2009Disclosure of Interests:Joep Welling Speakers bureau: Four times as a patient advocate for employees of BII and BI MIDI with a fixed amount of € 150,00 per occasion., Annelise Roennow: None declared, Maureen Sauvé Grant/research support from: Educational grants from Boehringer Ingelheim and Janssen., EDITH BROWN: None declared, Ilaria Galetti: None declared, Alex Gonzalez Consultant of: Payment made to the patient organisation (Scleroderma Research Foundation) for participation in advisory boards, Alexandra Paula Portales Guiraud: None declared, Ann Kennedy Grant/research support from: AS FESCA aisbl, Catarina Leite: None declared, Robert J. Riggs: None declared, Alison Zheng Grant/research support from: We get grants from Lorem Vascular; BI China,; Jianke Pharmaceutical Co., Ltd.; Kangjing Biological Co., Ltd.; COFCO Coca-Cola to organize national scleroderma meetings, offer patients service, holding academic meetings and other public activities, there is also a small part of the grants used to pay the workers in our organization., Consultant of: I worked as a paid consultant for BI. Pay-per-job., Speakers bureau: I was invited once to be a speaker at BI China's internal meeting and they paid me., Matea Perkovic Popovic: None declared, Annie Gilbert Consultant of: I have worked as a paid consultant with BI International for over 3 years, since Sept 2016., Lizette Moros Employee of: Lizette Moros is an employee of Boehringer Ingelheim, Kamila Sroka-Saidi Employee of: Paid employee of Boehringer Ingelheim., Thomas Schindler Employee of: Employee of Boehringer Ingelheim Pharma, Henrik Finnern Employee of: Paid employee of Boehringer Ingelheim

The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics:Analysis of the CREDENCE trial

Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon-like peptide-1 receptor agonists (all p(interaction) > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30-45 mL/min/1.73m(2): 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60-90 mL/min/1.73m(2)). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk

A national facility for biological cryo-electron microscopy

Three-dimensional electron microscopy is an enormously powerful tool for structural biologists. It is now able to provide an understanding of the molecular machinery of cells, disease processes and the actions of pathogenic organisms from atomic detail through to the cellular context. However, cutting-edge research in this field requires very substantial resources for equipment, infrastructure and expertise. Here, a brief overview is provided of the plans for a UK national three-dimensional electron-microscopy facility for integrated structural biology to enable internationally leading research on the machinery of life. State-of-the-art equipment operated with expert support will be provided, optimized for both atomic-level single-particle analysis of purified macromolecules and complexes and for tomography of cell sections. The access to and organization of the facility will be modelled on the highly successful macromolecular crystallography (MX) synchrotron beamlines, and will be embedded at the Diamond Light Source, facilitating the development of user-friendly workflows providing near-real-time experimental feedback

Crises and collective socio-economic phenomena: simple models and challenges

Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the Random Field Ising model (RFIM) indeed provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilising self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of RFIM-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can badly fail at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria to be reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several minor improvements along reviewers' comment

The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines

<p>Abstract</p> <p>Background</p> <p>Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification.</p> <p>Methods</p> <p>The prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526)</p> <p>Results</p> <p>There was a 7 fold difference in CKD_3-5prevalence between J-EPI and the other Asian eGFR formulae. CKD_3-5prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD_3-5was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD_3-5between CKD-EPI, S-MDRD and C-MDRD.</p> <p>Conclusions</p> <p>CKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.</p