Technology use in everyday life: Implications for designing for older users

This study examines the experience and attitudes of older adults towards technology and how they compare with younger age groups. Two hundred and thirty seven participants completed an extensive questionnaire exploring their daily lifestyle, use of technology, attitudes towards technology, and perceived difficulty of household devices. The main findings from the study were; (1) there was a strong motivation to learn or to continue learning to use computers by the older group; (2) social connectedness influenced how the older group used or would like to use technology and also why some preferred not to use it; and finally (3) there was an age-related increase in perceived difficulty for many household devices, however some devices maintained intergenerational usability. These finding can be used to inform the design of future intergenerational household technologies

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease

BACKGROUND: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. OBJECTIVES: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. ANIMALS: Records of 174 client-owned cats with IRIS stage 2-4 CKD. METHODS: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999-2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. RESULTS: Plasma tMg (reference interval, 1.73-2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, -0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35-5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54-5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04-154; P = .009) lost significance in multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation

A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAF(V600E) may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice

Set-based design of mechanical systems with design robustness integrated

This paper presents a method for parameter design of mechanical products based on a set-based approach. Set-based concurrent engineering emphasises on designing in a multi-stakeholder environment with concurrent involvement of the stakeholders in the design process. It also encourages flexibility in design through communication in terms of ranges instead of fixed point values and subsequent alternative solutions resulting from intersection of these ranges. These alternative solutions can then be refined and selected according to the designers’ preferences and clients’ needs. This paper presents a model and tools for integrated flexible design that take into account the manufacturing variations as well as the design objectives for finding inherently robust solutions using QCSP transformation through interval analysis. In order to demonstrate the approach, an example of design of rigid flange coupling with a variable number of bolts and a choice of bolts from ISO M standard has been resolved and demonstrated

Hungarian Pension System and its Reform

The goal of this study is to present an insider view on the pension reforms implemented in Hungary between 1996 and 2009. Both political economy as well as institutional economics will be used as the main approaches to analyse and explain the reform process and some of its effects. The following studies provide valuable insights: Palacios and Rocha (1998), Bokros and Dethier eds. (1998), Augusztinovics (1999), Augusztinovics et al. (2002), Simonovits (1999), (2000), (2008a), Czúcz and Pintér (2002), European Commission (2006), Gál (2006), Impavido and Rocha (2006), and Guardiancich (2008). The structure of the paper is as follows: Section 1 considers the legacy of the pension system. Section 2 summarises the debate on the pension reform and the basic decisions. Section 3 outlines the implementation of the pension reform, while Section 4 discusses the implementation problems. Section 5 describes the changes since the reform, while Section 6 analyses and Section 7 evaluates the reform. An Appendix discusses the issues of contribution rates.Hungary, pension reform, social security, private pension

Efficacy and safety of a combination therapy of atorvastatin and krill oil versus atorvastatin and niacin in dyslipidemia: a randomized, open, and comparator study

Background: Atherosclerotic cardiovascular disease is a major health problem, with CAD being the leading cause of mortality. Epidemiologic data strongly associate high CAD risk to elevated total and LDL cholesterol and low levels of HDL cholesterol. Combination therapy is often required to achieve multiple lipid treatment goals, and ≥50% reduction in low-density lipoprotein. Niacin/statin combination therapy may promote the cost-effective achievement of OLVs in several at-risk patient populations. Krill oil is extracted from Antarctic krill, Euphausia superba, a zooplankton crustacean rich in phospholipids. Krill oil significantly reduces total cholesterol, LDL, and triglycerides, and increase HDL levels and has been found to be effective in the management of hyperlipidemia and long-term regulation of blood lipids. The aim of this study is to compare the Efficacy and Safety of a combination therapy of statin and krill oil versus Statin and Niacin in dyslipidemia.Methods: 30 eligible patients were randomized in a 12 week, open-label, comparative (2-arm, 1:1), prospective study into 2 arms, the first receiving atorvastatin 10mg od and krill oil 500mg bid and the second receiving atorvastatin 10mg od and niacin 375mg od. The primary endpoint of the study was a comparative assessment of change in lipid profile (LDL, TG, HDL) from baseline and after 12 weeks. The secondary endpoint involved recording all the adverse effects during the study.Results: Analysis of the baseline and post 12 week lipid levels by non-parametric unpaired ‘t’ test (Mann-Whitney test) showed a statistically significant change in two of the lipid levels (i.e. LDL – p=0.0037 in favour of statin and niacin and HDL – p=0.0003 in favour of statin and niacin). However the triglyceride levels showed no significant change in the two groups (p=0.2452).Conclusions: In our study the conventional combination therapy of statin and niacin is found to be more efficacious than the newer statin and krill oil combination in lowering LDL levels and increasing HDL levels in dyslipidemic patients. A further study with a higher sample size could confirm the findings of this study

Physical constraints on accuracy and persistence during breast cancer cell chemotaxis

Directed cell motion in response to an external chemical gradient occurs in many biological phenomena such as wound healing, angiogenesis, and cancer metastasis. Chemotaxis is often characterized by the accuracy, persistence, and speed of cell motion, but whether any of these quantities is physically constrained by the others is poorly understood. Using a combination of theory, simulations, and 3D chemotaxis assays on single metastatic breast cancer cells, we investigate the links among these different aspects of chemotactic performance. In particular, we observe in both experiments and simulations that the chemotactic accuracy, but not the persistence or speed, increases with the gradient strength. We use a random walk model to explain this result and to propose that cells' chemotactic accuracy and persistence are mutually constrained. Our results suggest that key aspects of chemotactic performance are inherently limited regardless of how favorable the environmental conditions are

Mechanisms of myeloid cell recruitment and biomarker potential in interstitial lung diseases

Interstitial lung diseases (ILDs) are fibrotic disorders with chronic inflammation and fibrinogenesis leading to lung scaring and lung function decline. Ultimately, progressive pulmonary fibrosis results in altered pulmonary physiology, abnormal gas exchange, and organ failure. ILDs include known causes and idiopathic causes, as it is the case of idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). The most detrimental type of ILD is IPF in which anti-fibrotic drugs (nintedanib and pirfenidone) only decrease disease progression. For other ILD types, corticoid treatment helps to decrease exacerbation. Currently, clinical trials are evaluating the applicability of anti-fibrotic drugs for treating non-IPF ILDs. Therefore, mechanistic insights and in-depth cell characterization during tissue injury and remodeling in ILD are of great interest in the respiratory medical field. Circulating immune cell populations have been suggested to play a critical role in ILDs. For instance, mononuclear phagocytes are involved in the initiation, repair and regeneration of pulmonary fibrosis. Moreover, the close interaction between circulating and lung tissue-resident immune cells is critical to contribute to tissue homeostasis or lead to disease. However, precise myeloid phenotypes (e.g. myeloid-derived suppressor cells and monocytes) and their mechanisms of recruitment in ILDs have not yet been explored. In the first results chapter of this thesis, myeloid-derived suppressor cells (MDSC) abundance and function were investigated for the first time in IPF patients. For that, peripheral blood of 170 patients including IPF, non-IPF ILD, chronic obstructive pulmonary diseases (COPD) and controls were collected to characterize and quantify MDSC by flow cytometry. Circulating MDSC in IPF and non-IPF ILD were increased when compared with control. Moreover, cross sectional and longitudinal analysis of the abundance of MDSC inversely correlated with pulmonary function test in IPF only. IPF patients with high number of MDSC showed downregulation of co-stimulatory T cells signals quantified by qRT-PCR. Furthermore, MDSC were able to suppress lymphocytes CD4+ and CD8+ cells proliferation in vitro. Last, CD33 CD11b double positive cells, suggestive of MDSC, were found in neighboring fibrotic niches of the IPF lungs. Taking together, these results show that MDSC are potential biomarker for IPF and are suppressing T cell responses. In the second results chapter, we aimed at analyzing monocyte phenotype and recruitment from the blood to the lung tissue in ILD. Importantly, CX3CR1 expression on immune cells has been demonstrated to increase fibrosis features. For that, flow cytometry analysis of circulating monocytes was performed in 105 subjects (83 ILD, and 22 controls). Monocyte localization and abundance in the lung was assessed by immunofluorescence and flow cytometry analysis. For receptor-ligand function and transmigration pattern, monocytes were isolated from blood and cultured either alone or with endothelial cells. Here, we showed that classical monocytes (CM) were increased, while non-classical monocytes (NCM) were decreased in ILD: NSIP, hypersensitivity pneumonitis (HP) and connective tissue disease associated with ILD (CTD-ILD) compared with controls. Monocytes abundance positively correlated with lung function. Fractalkine levels, the ligand of CX3CR1, were higher in lung tissue than in plasma in ILD and also co-localized with bronchial ciliated cells. Fractalkine enhanced endothelial transmigration of NCM in ILD only. Flow cytometry and immunofluorescence staining showed increased NCM in ILD. NCM-derived cells in the ILD lungs co-stained with CX3CR1, M2-like and phagocytic markers. In summary, we show that epithelial-derived fractalkine drives the migration of NCM-CX3CR1 which provides an interstitial scavenger and phagocytic myeloid cells population in fibrotic ILD lungs