202 research outputs found
Health and labor productivity : the economic impact of onchocercal skin disease
Teams from two institutions studied the economic impact of health status on productivity and income. They studied whether onchocercal skin disease caused economic damage to the labor force at a coffee plantation in southwest Ethiopia, and how much. The research team estimated the daily wage equation for wage employees. Empirical analysis revealed that permanent male employees, the core of the plantation labor force, suffer significant losses in economic productivity (in the form of lower daily wages earned) as a result of onchocercal skin disease. Depending on the severity of onchocercal skin disease, and controlling for such factors as age, daily wages were 10 to 15 percent lower among those exhibiting skin-related problems.Environmental Economics&Policies,Disease Control&Prevention,Labor Policies,Health Economics&Finance,Public Health Promotion,Economic Theory&Research,Banks&Banking Reform,Environmental Economics&Policies,Youth and Governance,Health Monitoring&Evaluation
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From Wealth to Health: Modelling the Distribution of Income Per Capita at the Sub-National Level Using Night-Time Light Imagery
Background: Sub-national figures providing information about the wealth of the population are useful in defining the spatial distribution of both economic activity and poverty within any given country. Furthermore, since several health indicators such as life expectancy are highly correlated with household welfare, sub-national figures allow for the estimation of the distribution of these health indicators within countries when direct measurement is difficult. We have developed methods that utilize spatially distributed information, including night-time light imagery and population to model the distribution of income per capita, as a proxy for wealth, at the country and sub-national level to support the estimation of the distribution of correlated health indicators. Results: A first set of analysis are performed in order to propose a new global model for the prediction of income per capita at the country level. A second set of analysis is then confirming the possibility to transfer the country level approach to the sub-national level on a country by country basis before underlining the difficulties to create a global or regional models for the extrapolation of sub-national figures when no country data set exists. Conclusions: The methods described provide promising results for the extrapolation of national and sub-national income per capita figures. These results are then discussed in order to evaluate if the proposed methods could not represent an alternative approach for the generation of consistent country specific and/or global poverty maps disaggregated to some sub-national level
SMAD-signaling inhibition : potential for developing newer treatments for corneal fibrosis [abstract]
Transforming growth factor [beta] (TGFb) is known to cause fibrosis in the cornea following injury and/or infection. Effective reduction in corneal fibrosis has been reported by inhibiting TGFb activity. However, associated molecular mechanism is still unknown. The aim of study was to test the hypothesis that the alteration in SMAD signaling is a novel approach for treating corneal fibrosis using an established in vitro model
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Enhancing the Validity and Cross-cultural Comparability of Measurement in Survey Research
We address two long-standing survey research problems: measuring complicated concepts, such as political freedom and efficacy, that researchers define best with reference to examples; and what to do when respondents interpret identical questions in different ways. Scholars have long addressed these problems with approaches to reduce incomparability, such as writing more concrete questions—with uneven success. Our alternative is to measure directly response category incomparability and to correct for it. We measure incomparability via respondents’ assessments, on the same scale as the self-assessments to be corrected, of hypothetical individuals described in short vignettes. Because the actual (but not necessarily reported) levels of the vignettes are invariant over respondents, variability in vignette answers reveals incomparability. Our corrections require either simple recodes or a statistical model designed to save survey administration costs. With analysis, simulations, and cross-national surveys, we show how response incomparability can drastically mislead survey researchers and how our approach can alleviate this problem.Governmen
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Comparability of Self Rated Health: Cross Sectional Multi-Country Survey Using Anchoring Vignettes
Objective: To examine differences in expectations for health using anchoring vignettes, which describe fixed levels of health on dimensions such as mobility. Design: Cross sectional survey of adults living in the community. Setting: China, Myanmar, Sri Lanka, Pakistan, Turkey, and United Arab Emirates. Participants: 3012 men and women aged 18 years and older (self ratings); subsample of 406 (vignette ratings). Main outcome measures: Self rated mobility levels and ratings of hypothetical vignettes using the same questions and response categories. Results: Consistent rankings of vignettes are evidence that vignettes are understood in similar ways in different settings, and internal consistency of orderings on two mobility questions indicates good comprehension. Variation in vignette ratings across age groups suggests that expectations for mobility decline with age. Comparison of responses to two different mobility questions supports the assumption that individual ratings of hypothetical vignettes relate to expectations for health in similar ways as self assessments. Conclusions: Anchoring vignettes could provide a powerful tool for understanding and adjusting for the influence of different health expectations on self ratings of health. Incorporating anchoring vignettes in surveys can improve the comparability of self reported measures
Vector Delivery Technique Affects Gene Transfer in the Cornea \u3cem\u3ein vivo\u3c/em\u3e
Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.
Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for 10 s with a 5 s interval after each 10 s hair dryer application. Thereafter, balanced salt solution (BSS) was topically applied immediately on the cornea for 2 min using a custom-cloning cylinder. The absorbed BSS was quantified using Hamilton microsyringes. The adenoassociated virus 8 (AAV8) vector (1.1×108 genomic copies/μl) expressing marker gene was used to study the effect of corneal drying on gene transfer. Animals were sacrificed on day 14 and gene expression was analyzed using commercial staining kit. Morphological changes and infiltration of inflammatory cells were examined with H & E staining and immunocytochemistry.
Results: Mice, rabbit or human corneas subjected to no or 10 s drying showed 6%–8% BSS absorption whereas 20, 30, or 50 s corneal drying showed significantly high 14%–19% (pin vivowith mild-to-moderate changes in corneal morphology. The 30 s of drying also showed significantly (pin vivowithout jeopardizing corneal morphology whereas 10 or 20 s drying showed moderate degree of gene transfer with no altered corneal morphology. Corneas that underwent 50 s drying showed high CD11b-positive cells (p
Conclusions: Controlled corneal drying with hair dryer increases vector absorption significantly. The dispensing of efficacious AAV serotype into cornea with optimized minimally invasive topical application technique could provide high and targeted expression of therapeutic genes in the stroma in vivo without causing significant side effects
Gene transfer technology : a tool for studying gene function and role in corneal pathogenesis [abstract]
Transforming growth factor β (TGFb) is associated with many corneal pathologies, diseases and dystrophies. The function of TGFb in adult corneas cannot be studied using conventional transgenic approach because TGFb1 and TGFb2 deficient transgenic animals suffer multiple inflammatory diseases, severe developmental defects, and death by 3-4 weeks of age. This study tested the hypothesis that selective tissue-targeted gene transfer approaches will permit examination of TGFb gene function in the adult cornea without altering TGFb expression in vital organs
Attenuation of corneal myofibroblast development through nanoparticle-mediated soluble transforming growth factor-β type II receptor (sTGFβRII) gene transfer
Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.
Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were generated from donor corneas; myofibroblasts and fibrosis were induced with TGFβ1 (1 ng/ml) stimulation employing serum-free conditions. The sTGFβRII conjugated to the Fc portion of human immunoglobulin gene was introduced into HCF using either PEI-DNA nanoparticles or Lipofectamine. Suitable negative and positive controls to compare selected nanoparticle and therapeutic gene efficiency were included. Delivered gene copies and mRNA (mRNA) expression were quantified with real-time quantitative PCR (qPCR) and protein with enzyme-linked immunosorbent assay (ELISA). The changes in fibrosis parameters were quantified by measuring fibrosis marker α-smooth muscle actin (SMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Cytotoxicity was determined using cellular viability, proliferation, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
Results: PEI readily bound to plasmids to form nanoparticular polyplexes and exhibited much greater transfection efficiency (p<0.01) than the commercial reagent Lipofectamine. The PEI-DNA-treated cultures showed 4.5×10[superscript 4] plasmid copies/µg DNA in real-time qPCR and 7,030±87 pg/ml sTGFβRII protein in ELISA analyses, whereas Lipofectamine-transfected cultures demonstrated 1.9×10[superscript 3] gene copies/µg DNA and 1,640±100 pg/ml sTGFβRII protein during these assays. The PEI-mediated sTGFβRII delivery remarkably attenuated TGFβ1-induced transdifferentiation of corneal fibroblasts to myofibroblasts in cultures, as indicated by threefold lower levels of SMA mRNA (p<0.01) and significant inhibition of SMA protein (up to 96±3%; p<0.001 compared to no-gene-delivered cultures) in immunocytochemical staining and immunoblotting. The nanoparticle-mediated delivery of sTGFβRII showed significantly better antifibrotic effects than the Lipofectamine under similar experimental conditions. However, the inhibition of myofibroblast in HCF cultures by sTGFβRII overexpression by either method was significantly higher than the naked vector transfection. Furthermore, PEI- or Lipofectamine-mediated sTGFβRII delivery into HCF did not alter cellular proliferation or phenotype at 12 and 24 h post-treatment. Nanoparticles treated with HCF showed more than 90% cellular viability and very low cell death (2–6 TUNEL+ cells), suggesting that the tested doses of PEI-nanoparticles do not induce significant cell death.
Conclusions: This study demonstrated that PEI-DNA nanoparticles are an attractive vector for the development of nonviral corneal gene therapy approaches and that the sTGFβRII gene delivery into keratocytes could be used to control corneal fibrosis in vivo.National Institutes of Health (U.S.) (RO1EB000244
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