E-democracy: exploring the current stage of e-government

Governments around the world have been pressured to implement e-Government programs in order to improve the government-citizen dialogue. The authors of this article review prior literature on such efforts to find if they lead to increased democratic participation ("e-Democracy") for the affected citizens, with a focus on the key concepts of transparency, openness, and engagement. The authors find that such efforts are a starting point toward e-Democracy, but the journey is far from complete

The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research

In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unafected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These fndings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, ofers unique opportunities for drug discovery and fundamental research into preclinical AD

ATP13A2 deficiency disrupts lysosomal polyamine export

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome—a parkinsonism with dementia1—and early-onset Parkinson’s disease2. ATP13A2 offers protection against genetic and environmental risk factors of Parkinson’s disease, whereas loss of ATP13A2 compromises lysosomes3. However, the transport function of ATP13A2 in lysosomes remains unclear. Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system

Availability, price and affordability of cardiovascular medicines: A comparison across 36 countries using WHO/HAI data

<p>Abstract</p> <p>Background</p> <p>The global burden of cardiovascular disease (CVD) continues to rise. Successful treatment of CVD requires adequate pharmaceutical management. The aim was to examine the availability, pricing and affordability of cardiovascular medicines in developing countries using the standardized data collected according to the World Health Organization/Health Action International methodology.</p> <p>Methods</p> <p>The following medicines were included: atenolol, captopril, hydrochlorothiazide, losartan and nifedipine. Data from 36 countries were analyzed. Outcome measures were percentage availability, price ratios to international reference prices and number of day's wages needed by the lowest-paid unskilled government worker to purchase one month of chronic treatment. Patient prices were adjusted for inflation and purchasing power, procurement prices only for inflation. Data were analyzed for both generic and originator brand products and the public and private sector and summarized by World Bank Income Groups.</p> <p>Results</p> <p>For all measures, there was great variability across surveys. The overall availability of cardiovascular medicines was poor (mean 26.3% in public sector, 57.3% private sector). Procurement prices were very competitive in some countries, whereas others consistently paid high prices. Patient prices were generally substantially higher than international references prices; some countries, however, performed well. Chronic treatment with anti-hypertensive medication cost more than one day's wages in many cases. In particular when monotherapy is insufficient, treatment became unaffordable.</p> <p>Conclusions</p> <p>The results of this study emphasize the need of focusing attention and financing on making chronic disease medicines accessible, in particular in the public sector. Several policy options are suggested to reach this goal.</p

A STEPPING STONE TOWARDS KNOWLEDGE BASED MAINTENANCE

Maintenance decision making becomes more and more a management concern. Some decades ago, maintenance was still often considered as an unavoidable side effect of production. The perception of maintenance has evolved considerably. One of the current issues is the maintenance concept, being the mix of maintenance interventions and the general framework for determining this mix. In this paper we describe a modular framework, called Knowledge Based Maintenance, for developing a customised maintenance concept. After describing the general framework and its decision support use, some case experiences are given. This experience covers some elements of the proposed framework

Amylose-lipid complexes as controlled lipid release agents during starch gelatinization and pasting

The effect of amylose-lipid (AM-L) complexes consisting of amylose populations with different peak degrees of polymerization (DP) and complexed with glyceryl monostearate (GMS) or docosanoic acid (C22) on the pasting properties of wheat and rice starches was evaluated with a rapid visco analyzer (RVA). AM-L complexes were formed by both (i) addition of lipids to amylose fractions with peak DP 20, 60, 400, or 950 at 60 degrees C or (ii) potato phosphorylase-catalyzed amylose synthesis in the presence of lipids. All AM-L complexes affected pasting properties in line with their dissociation characteristics. AM-L complexes therefore have potential as "controlled lipid release agents" with effects markedly different from those observable with emulsifier addition in starch pasting. More in particular, short chain AM-L complexes resulted in a starch pasting behavior comparable to that of cross-linked starch, as evidenced by reduced granule swelling, good viscosity stability in conditions of high temperature and shear, and a stable cold paste viscosity.status: publishe