Identification Techniques Applied to a Passive Elasto-magnetic Suspension

The paper presents an experimental passive elasto-magnetic suspension based on rare-earth permanent magnets, characterized by negligible dependence on mass of its natural frequency. The nonlinear behaviour of this system, equipped with a traditional linear elastic spring coupled to a magnetic spring, is analysed in time domain, for non-zero initial conditions, and in frequency domain, by applying sweep excitations to the test rig base. The dynamics of the system is very complex in dependence of the magnetic contribution, showing both hardening behaviour in the elasto-magnetic setup, and softening motion amplitude dependent behaviour in the purely magnetic case. Hence it is necessary to adopt nonlinear identification techniques, such as non-parametric restoring force mapping method and direct parametric estimation technique, in order to identify the system parameters in the different configurations. Finally, it is discussed the ability of identified versus analytical models in reproducing the nonlinear dependency of frequency on motion amplitude and the presence of jump phenomen

The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding

Hashimoto’s thyroiditis (HT) is part of a spectrum of thyroid autoimmune conditions and this review provides an update on the latest developments in the field. HT has a genetic predisposition with a number of immune-related and thyroid-specific genes conferring disease susceptibility. However, disentangling genes with protective and predisposing effect is a complex process that requires further work. The recent increase in the incidence of HT implicates environmental factors in disease pathogenesis including improved hygiene, increased dietary iodine intake, new treatment modalities and chemical agents. Additional unmodifiable predisposing factors include stress, climate, age and gender. Both cellular and humoral immunity play a role in HT pathogenesis. Defects in T regulatory cells and increased activation of follicular helper T cells may have a role in disease initiation/perpetuation. Infiltrating lymphocytes can be directly cytotoxic to thyroid follicular cells (TFC) or may affect cell viability/function indirectly through cytokine production, which alters TFC integrity and modulates their metabolic and immune function. Thyroid peroxidase and thyroglobulin antibodies are present in the majority of HT patients and help with management decisions. Antibodies against the sodium iodide symporter and pendrin are present in a minority with little known about their clinical relevance. In addition to immune cells, recent work has identified DNA fragments, generated following cell death, and micro RNA as potential factors in HT pathogenesis. Despite the large number of studies, the mechanistic pathways in HT are still not fully understood and further work is required to enhance our knowledge and identify novel preventative and therapeutic clinical targets

Theory of collective firing induced by noise or diversity in excitable media

5 pages.-- PACS numbers: 05.45.Xt, 05.40.-a, 02.50.-r.-- Final full-text of the paper available at: http://dx.doi.org/10.1103/PhysRevE.75.016203.Large variety of physical, chemical, and biological systems show excitable behavior, characterized by a nonlinear response under external perturbations: only perturbations exceeding a threshold induce a full system response (firing). It has been reported that in coupled excitable identical systems noise may induce the simultaneous firing of a macroscopic fraction of units. However, a comprehensive understanding of the role of noise and that of natural diversity present in realistic systems is still lacking. Here we develop a theory for the emergence of collective firings in nonidentical excitable systems subject to noise. Three different dynamical regimes arise: subthreshold motion, where all elements remain confined near the fixed point; coherent pulsations, where a macroscopic fraction fire simultaneously; and incoherent pulsations, where units fire in a disordered fashion. We also show that the mechanism for collective firing is generic: it arises from degradation of entrainment originated either by noise or by diversity.The authors acknowledge financial support by the Ministerio de Educación y Ciencia (Spain), FEDER Contract Nos. FIS2004-5073, FIS2004-953, BFM2001-0341 and the EU NoE BioSim (LSHB-CT-2004-005137)

BβArg448Lys polymorphism is associated with altered fibrin clot structure and fibrinolysis in type 2 diabetes

Both type 2 diabetes (T2DM) and Bβ448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BβArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BβArg448Lys on fibrin network characteristics in T2DM. Secondary aims investigated interactions between gender and BβArg448Lys substitution in relation to fibrin clot properties and vascular disease. Genotyping for BβArg448Lys and dynamic clot studies were carried out on 822 T2DM patients enrolled in the Edinburgh Type 2 Diabetes Study. Turbidimetric assays of individual plasma samples analysed fibrin clot characteristics with additional experiments conducted on clots made from purified fibrinogen, further examined by confocal and electron microscopy. Plasma clot lysis time in Bβ448Lys was longer than Bβ448Arg variant (mean ± SD; 763 ± 322 and 719 ± 351 seconds [s], respectively; p<0.05). Clots made from plasma-purified fibrinogen of individuals with Arg/Arg, Arg/Lys and Lys/Lys genotypes showed differences in fibre thickness (46.75 ± 8.07, 38.40 ± 6.04 and 25 ± 4.99 nm, respectively; p<0.001) and clot lysis time (419 ± 64, 442 ± 87 and 517 ± 65 s, respectively; p=0.02), directly implicating the polymorphism in the observed changes. Women with Bβ448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bβ448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies

IL-14 and IL-16 are expressed in the thyroid of patients with either Graves' disease or Hashimoto's thyroiditis

OBJECTIVES: Cytokines have an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The aim of the current study was to analyse the expression of interleukin (IL)-14 and IL-16 in the thyroid tissue of patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) or multi-nodular goitre (MNG) and in that of normal individuals, in patients' intra-thyroidal CD4(+) and CD8(+) T cells, and in patient and normal cultured thyroid follicular cells. METHODS: The expression of IL-14 and IL-16 mRNA and protein was investigated using reverse transcription-polymerase chain reaction (RT-PCR) amplification, and western blotting and ELISAs, respectively. RESULTS: IL-14 mRNA expression was detected in thyroid tissue from 8/9 GD, 3/4 HT and 3/13 MNG patients and 1/6 normal individuals, and IL-16 mRNA expression in thyroid tissue from 9/9 GD, 4/4 HT and 9/13 MNG patients and 4/6 normal individuals. IL-14 mRNA expression was detected in intra-thyroidal CD4(+) and CD8(+) T cells from 2/2 GD and 2/2 HT patients, while IL-16 mRNA was detected in samples from 1/2 HT but not in those from either GD patients. IL-14 and IL-16 mRNA expression was found in thyroid follicular cells derived from 2/2 patients with GD and 1/1 normal individual. IL-14 protein was detected in thyroid tissue from 6/6 GD, 1/1 HT and 0/6 MNG patients and 0/6 normal individuals, and IL-16 protein in thyroid tissue from 6/6 GD, 1/1 HT and 1/6 MNG patients and 0/6 normal individuals. Expression of IL-14 protein was stimulated in thyroid follicular cells derived from two GD patients and one normal individual by peripheral blood mononuclear cell (PBMC)-conditioned medium. Treatment of thyrocytes from two GD patients and one normal individual with PBMC-conditioned medium and tumour necrosis factor (TNF)-α stimulated IL-16 protein expression. In normal thyrocytes, IL-16 protein synthesis was induced also by IL-1β, IL-17A, IL-4 and transforming growth factor (TGF)-β. CONCLUSIONS: The data provide evidence that the intra-thyroidal production of IL-14 and IL-16 is associated with the pathogenesis of autoimmune thyroid disease. Thyroid follicular cells display the ability to express IL-14 and IL-16 mRNA and can be stimulated to express IL-16 protein, by a panel of cytokines, and IL-14 protein, by as yet unidentified factors. This article is protected by copyright. All rights reserved

How Can We Realize the Clinical Benefits of Continuous Glucose Monitoring?

Controlling glycemia in diabetes remains key to prevent complications in this condition. However, glucose levels can undergo large fluctuations secondary to daily activities, consequently creating management difficulties. The current review summarizes the basics of glucose management in diabetes by addressing the main glycemic parameters. The advantages and limitation of HbA1c, the gold standard measure of glucose control, are discussed together with the clinical importance of hypoglycemia and glycemic variability. The review subsequently moves focus to glucose monitoring techniques in diabetes, assessing advantages and limitations. Monitoring glucose levels is crucial for effective and safe adjustment of hypoglycemic therapy, particularly in insulin users. Self-monitoring of blood glucose (SMBG), based on capillary glucose testing, remains one of the most widely used methods to monitor glucose levels, given the relative accuracy, familiarity, and manageable costs. However, patient inconvenience and the sporadic nature of SMBG limit clinical effectiveness of this approach. In contrast, continuous glucose monitoring (CGM) provides a more comprehensive picture of glucose levels, but these systems are expensive and require constant calibration which, together with concerns over accuracy of earlier devices, restrict CGM use to special groups of patients. The newer flash continuous glucose monitoring (FCGM) system, which is more affordable than conventional CGM devices and does not require calibration, offers an alternative glucose monitoring strategy that comprehensively analyzes glucose profile while sparing patients the inconvenience of capillary glucose testing for therapy adjustment or CGM calibration. The fast development of new CGM devices will gradually displace SMBG as the main glucose testing method. Avoiding the inconvenience of SMBG and optimizing glycemia through alternative glucose testing strategies will help to reduce the risk of complications and improve quality of life in patients with diabetes

Diabetes mellitus, microalbuminuria, and subclinical cardiac disease: Identification and monitoring of individuals at risk of heart failure

Background-Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. Methods and Results-In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR > 2.5 mg/mol in males and > 3.5 mg/mol in females, ≥2 measurements, no previous renin- angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E0 measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels. Conclusions-Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by subclinical changes in tissue structure and function

Coronary artery disease-associated genetic variants and biomarkers of inflammation

Introduction: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers. Methods: We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. Results: The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score. Conclusions: In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers

Improving Project Management Through a Shared Understanding of Project Risk and Return

Organizations are increasingly interested in improving IT project management in a multi-project or portfolio environment. This research presents a project assessment methodology based on defining a common risk-return vocabulary between IT and business stakeholders. The proposed methodology could help project managers highlight any differences in perceptions between business and IT that might impact the project negatively, if not managed properly. The use of the assessment methodology in a multi-project environment is illustrated using data from a diversified company. A number of managerial implications are then drawn highlighting how the methodology could be useful in practice