257 research outputs found

    A proposed approach to the application of nonlinear irreversible thermodynamics to fracture in composite materials

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    The fracture criteria upon which most fracture mechanics is based involves an energy balance that is not appropriate for the fracture mechanics of viscoelastic materials such as polymer matrix composites. A more appropriate criterion based upon nonequilibrium thermodynamics and involving a power balance rather than an energy balance is proposed. This crierion is based upon a reformulation of the second law of thermodynamics which focuses attention on the total Legendre transform of energy expressed as a functional over time and space. This excess energy functional can be shown to be equivalent to the Rice J integral if the only irreversible process is the propogation of a single crack completely through the thickness of the specimen and if the crack propogation is assured to be independent of time. For the more general case of more than one crack in a viscoelastic medium integration over both time and space is required. Two experimentally measurable parameters are proposed which should permit the evaluation of this more general fracture criterion

    Oral health awareness and care preferences in patients with diabetes : a qualitative study

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    Background People with type 2 diabetes have an increased risk of oral health problems; however, oral health is currently not included in structured diabetes reviews and education in the UK. Aim and Objectives This study explores the patient experience related to oral health and diabetes, especially in relation to: • Awareness of the link between oral health and diabetes and oral self care needs • Interaction with health professionals in dental and general practice • Preferences for receiving oral health information and education Methods This nested qualitative study involved semi-structured telephone interviews with a purposive sample of 20 participants from a questionnaire study on oral health awareness in patients with diabetes. Interview transcripts were analysed using a thematic framework approach. Results Participants were mostly unaware of the link between oral health and diabetes. Those that had been made aware by a health professional were not given concrete self care advice. Interactions with dental professionals were often limited to informing the dental practice of their diagnosis and current medication. Most participants were in favour of dentists screening for diabetes, but as their general practice was the hub for diabetes care, they felt GPs or nurses should provide oral health information and discuss oral health with patients. Conclusions Written information regarding diabetes and its possible effects on oral health needs to be more readily available to people with diabetes, especially at diagnosis. There may be a place for introducing a structured oral health question in routine diabetes reviews

    Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

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    Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease

    Patients with severe acute‐on‐chronic liver failure are disadvantaged by model for end‐stage liver disease‐based organ allocation policy

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    Background: Mortality for patients with acute‐on‐chronic liver failure (ACLF) may be underestimated by the model for end‐stage liver disease‐sodium (MELD‐Na) score. / Aim: To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD‐Na score ≥35, and therefore having similar priority for liver transplantation. / Methods: We analysed the United Network for Organ Sharing (UNOS) database, years 2010‐2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression. / Results: We identified 6342 candidates at listing with a MELD‐Na score ≥35, of whom 3122 had ACLF‐3. Extra‐hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF‐3 had a significantly higher risk for 90‐day waitlist mortality (Sub‐hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12‐1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF‐3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20‐1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54‐3.58) was associated with increased waitlist death. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54‐0.68). The Share 35 rule was associated with reduced 90‐day waitlist mortality among the full cohort of patients listed with ACLF‐3 and MELD‐Na score ≥35 (SHR = 0.59; 95% CI 0.49‐0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58‐1.02). / Conclusion: The MELD‐Na score disadvantages patients with ACLF‐3, both with and without extra‐hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration

    Extreme events in time series aggregation: A case study for optimal residential energy supply systems

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    To account for volatile renewable energy supply, energy systems optimization problems require high temporal resolution. Many models use time-series clustering to find representative periods to reduce the amount of time-series input data and make the optimization problem computationally tractable. However, clustering methods remove peaks and other extreme events, which are important to achieve robust system designs. We present a general decision framework to include extreme events in a set of representative periods. We introduce a method to find extreme periods based on the slack variables of the optimization problem itself. Our method is evaluated and benchmarked with other extreme period inclusion methods from the literature for a design and operations optimization problem: a residential energy supply system. Our method ensures feasibility over the full input data of the residential energy supply system although the design optimization is performed on the reduced data set. We show that using extreme periods as part of representative periods improves the accuracy of the optimization results by 3% to more than 75% depending on system constraints compared to results with clustering only, and thus reduces system cost and enhances system reliability

    Measurement of the CMS Magnetic Field

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    The measurement of the magnetic field in the tracking volume inside the superconducting coil of the Compact Muon Solenoid (CMS) detector under construction at CERN is done with a fieldmapper designed and produced at Fermilab. The fieldmapper uses 10 3-D B-sensors (Hall probes) developed at NIKHEF and calibrated at CERN to precision 0.05% for a nominal 4 T field. The precise fieldmapper measurements are done in 33840 points inside a cylinder of 1.724 m radius and 7 m long at central fields of 2, 3, 3.5, 3.8, and 4 T. Three components of the magnetic flux density at the CMS coil maximum excitation and the remanent fields on the steel-air interface after discharge of the coil are measured in check-points with 95 3-D B-sensors located near the magnetic flux return yoke elements. Voltages induced in 22 flux-loops made of 405-turn installed on selected segments of the yoke are sampled online during the entire fast discharge (190 s time-constant) of the CMS coil and integrated offline to provide a measurement of the initial magnetic flux density in steel at the maximum field to an accuracy of a few percent. The results of the measurements made at 4 T are reported and compared with a three-dimensional model of the CMS magnet system calculated with TOSCA.Comment: 4 pages, 5 figures, 15 reference

    Expression of the chemokine receptor CCR6 in human renal inflammation

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    Background. Nodular inflammatory cell infiltrates with defined microarchitecture, i.e. tertiary lymphoid organs, develop in the tubulointerstitium during chronic renal inflammation. CCR6 and the corresponding ligand CCL20 are involved in the formation of gut-associated lymphatic tissue. We hypothesized that CCR6 might be involved in the formation of nodular infiltrates in the kidney. Methods. CCR6- and CD20-positive B cells were localized in renal biopsies with IgA nephropathy (n = 13), membranous nephropathy (n = 12), crescentic glomerulonephritis (cGN, n = 11) and chronic interstitial nephritis (n = 13), and in pre-implantation biopsies as controls (n = 8). The mRNA expression of CCR6 and the ligand CCL20 was quantified by real-time RT-PCR in 51 renal biopsies of the same disease entities. Results. In the pre-transplant biopsies, CCR6 was expressed by endothelial cells of peritubular and glomerular capillaries. In patients with glomerulonephritis, infiltrating cells were positive particularly in areas of nodular inflammatory cell accumulations. A major part of the CCR6-positive cells were CD20-positive B cells, but a part of the CD3-positive T cells were also found to be positive. The constitutive expression of CCR6 on the endothelium of glomerular capillaries was lost in biopsies with progressive injury. Tubular epithelial cells expressed CCR6 in inflamed kidneys, most commonly on the basolateral side. Conclusions. CCR6 and the corresponding ligand CCL20 might therefore be involved in the recruitment of T and B cells to organized nodular infiltrates in chronic renal inflammation. The functional role of endothelial CCR6 needs to be evaluated in further studie

    Anti-GBM Glomerulonephritis Involves IL-1 but Is Independent of NLRP3/ASC Inflammasome-Mediated Activation of Caspase-1

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    IL-1β and IL-18 are proinflammatory cytokines that contribute to renal immune complex disease, but whether IL-1β and IL-18 are mediators of intrinsic glomerular inflammation is unknown. In contrast to other cytokines the secretion of IL-1β and IL-18 requires a second stimulus that activates the inflammasome-ASC-caspase-1 pathway to cleave pro-IL-1β and -IL-18 into their mature and secretable forms. As the NLRP3 inflammasome and caspase-1 were shown to contribute to postischemic and postobstructive tubulointerstitial inflammation, we hypothesized a similar role for NLRP3, ASC, and caspase-1 in glomerular immunopathology. This concept was supported by the finding that lack of IL-1R1 reduced antiserum-induced focal segmental necrosis, crescent formation, and tubular atrophy when compared to wildtype mice. Lack of IL-18 reduced tubular atrophy only. However, NLRP3-, ASC- or caspase-1-deficiency had no significant effect on renal histopathology or proteinuria of serum nephritis. In vitro studies with mouse glomeruli or mesangial cells, glomerular endothelial cells, and podocytes did not reveal any pro-IL-1β induction upon LPS stimulation and no caspase-1 activation after an additional exposure to the NLRP3 agonist ATP. Only renal dendritic cells, which reside mainly in the tubulointerstitium, expressed pro-IL-1β and were able to activate the NLRP3-caspase-1 axis and secrete mature IL-1β. Together, the NLRP3-ASC-caspase-1 axis does not contribute to intrinsic glomerular inflammation via glomerular parenchymal cells as these cannot produce IL-1β during sterile inflammation

    Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

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    Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base
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