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121.
Gabriela B. Gomez Nicola Foster Daniella Brals Heleen E. Nelissen Oladimeji A. Bolarinwa Marleen E. Hendriks Alexander C. Boers Diederik van Eck Nicole Rosendaal Peju Adenusi Kayode Agbede Tanimola M. Akande Michael Boele van Hensbroek Ferdinand W. Wit Catherine A. Hankins Constance Schultsz 《PloS one》2015,10(9)
Background
While the Nigerian government has made progress towards the Millennium Development Goals, further investments are needed to achieve the targets of post-2015 Sustainable Development Goals, including Universal Health Coverage. Economic evaluations of innovative interventions can help inform investment decisions in resource-constrained settings. We aim to assess the cost and cost-effectiveness of maternal care provided within the new Kwara State Health Insurance program (KSHI) in rural Nigeria.Methods and Findings
We used a decision analytic model to simulate a cohort of pregnant women. The primary outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario compared to the current standard of care. Intervention cost from a healthcare provider perspective included service delivery costs and above-service level costs; these were evaluated in a participating hospital and using financial records from the managing organisations, respectively. Standard of care costs from a provider perspective were derived from the literature using an ingredient approach. We generated 95% credibility intervals around the primary outcome through probabilistic sensitivity analysis (PSA) based on a Monte Carlo simulation. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the base case separately through a scenario analysis. Finally, we assessed the sustainability and feasibility of this program’s scale up within the State’s healthcare financing structure through a budget impact analysis. The KSHI scenario results in a health benefit to patients at a higher cost compared to the base case. The mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost-effective compared to a willingness-to-pay threshold of one gross domestic product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval 21.9–152.3), during one-way sensitivity analyses, and when cost, quality, cost and utilization parameters of the base case scenario were changed. The sustainability of this program’s scale up by the State is dependent on further investments in healthcare.Conclusions
This study provides evidence that the investment made by the KSHI program in rural Nigeria is likely to have been cost-effective; however, further healthcare investments are needed for this program to be successfully expanded within Kwara State. Policy makers should consider supporting financial initiatives to reduce maternal mortality tackling both supply and demand issues in the access to care. 相似文献122.
123.
Extraction of extracellular polymeric substances (EPS) from anaerobic granular sludges: comparison of chemical and physical extraction protocols 总被引:9,自引:0,他引:9
Paul D’Abzac François Bordas Eric Van Hullebusch Piet N. L. Lens Gilles Guibaud 《Applied microbiology and biotechnology》2010,85(5):1589-1599
The characteristics of the extracellular polymeric substances (EPS) extracted with nine different extraction protocols from
four different types of anaerobic granular sludge were studied. The efficiency of four physical (sonication, heating, cationic
exchange resin (CER), and CER associated with sonication) and four chemical (ethylenediaminetetraacetic acid, ethanol, formaldehyde
combined with heating, or NaOH) EPS extraction methods was compared to a control extraction protocols (i.e., centrifugation).
The nucleic acid content and the protein/polysaccharide ratio of the EPS extracted show that the extraction does not induce
abnormal cellular lysis. Chemical extraction protocols give the highest EPS extraction yields (calculated by the mass ratio
between sludges and EPS dry weight (DW)). Infrared analyses as well as an extraction yield over 100% or organic carbon content
over 1 g g−1 of DW revealed, nevertheless, a carry-over of the chemical extractants into the EPS extracts. The EPS of the anaerobic granular
sludges investigated are predominantly composed of humic-like substances, proteins, and polysaccharides. The EPS content in
each biochemical compound varies depending on the sludge type and extraction technique used. Some extraction techniques lead
to a slightly preferential extraction of some EPS compounds, e.g., CER gives a higher protein yield. 相似文献
124.
Hugo Alves Ursula Munoz‐Najar Jan De Wit Auke J. S. Renard Jan H. J. Hoeijmakers John M. Sedivy Clemens Van Blitterswijk Jan De Boer 《Journal of cellular and molecular medicine》2010,14(12):2729-2738
Human mesenchymal stromal cells (hMSCs) represent an attractive cell source for clinic applications. Besides being multi‐potent, recent clinical trials suggest that they secrete both trophic and immunomodulatory factors, allowing allogenic MSCs to be used in a wider variety of clinical situations. The yield of prospective isolation is however very low, making expansion a required step toward clinical applications. Unfortunately, this leads to a significant decrease in their stemness. To identify the mechanism behind loss of multi‐potency, hMSCs were expanded until replicative senescence and the concomitant molecular changes were characterized at regular intervals. We observed that, with time of culture, loss of multi‐potency was associated with both the accumulation of DNA damage and the respective activation of the DNA damage response pathway, suggesting a correlation between both phenomena. Indeed, exposing hMSCs to DNA damage agents led to a significant decrease in the differentiation potential. We also showed that hMSCs are susceptible to accumulate DNA damage upon in vitro expansion, and that although hMSCs maintained an effective nucleotide excision repair activity, there was a progressive accumulation of DNA damage. We propose a model in which DNA damage accumulation contributes to the loss of differentiation potential of hMSCs, which might not only compromise their potential for clinical applications but also contribute to the characteristics of tissue ageing. 相似文献
125.
Kommadath A Mulder HA de Wit AA Woelders H Smits MA Beerda B Veerkamp RF Frijters AC Te Pas MF 《Animal : an international journal of animal bioscience》2010,4(8):1297-1307
Intensive selection for high milk yield in dairy cows has raised production levels substantially but at the cost of reduced fertility, which manifests in different ways including reduced expression of oestrous behaviour. The genomic regulation of oestrous behaviour in bovines remains largely unknown. Here, we aimed to identify and study those genes that were associated with oestrous behaviour among genes expressed in the bovine anterior pituitary either at the start of oestrous cycle or at the mid-cycle (around day 12 of cycle), or regardless of the phase of cycle. Oestrous behaviour was recorded in each of 28 primiparous cows from 30 days in milk onwards till the day of their sacrifice (between 77 and 139 days in milk) and quantified as heat scores. An average heat score value was calculated for each cow from heat scores observed during consecutive oestrous cycles excluding the cycle on the day of sacrifice. A microarray experiment was designed to measure gene expression in the anterior pituitary of these cows, 14 of which were sacrificed at the start of oestrous cycle (day 0) and 14 around day 12 of cycle (day 12). Gene expression was modelled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model on data from day 0 cows alone (analysis 1), day 12 cows alone (analysis 2) and the combined data from day 0 and day 12 cows (analysis 3). Genes whose expression patterns showed significant linear or non-linear relationships with average heat scores were identified in all three analyses (177, 142 and 118 genes, respectively). Gene ontology terms enriched among genes identified in analysis 1 revealed processes associated with expression of oestrous behaviour whereas the terms enriched among genes identified in analysis 2 and 3 were general processes which may facilitate proper expression of oestrous behaviour at the subsequent oestrus. Studying these genes will help to improve our understanding of the genomic regulation of oestrous behaviour, ultimately leading to better management strategies and tools to improve or monitor reproductive performance in bovines. 相似文献
126.
Jan Bartacek Isabella Manconi Gerardo Sansone Roberta Murgia Piet N.L. Lens 《Nitric oxide》2010,22(2):101-105
Hydrogen sulfide (H2S) inhibits the last step of the denitrification process, i.e. the reduction of nitrous oxide (N2O) to dinitrogen gas (N2), both in natural environments (marine sediments) and industrial processes (activated sludge, methanogenic sludge, BioDeNOx process). In a previously published study, we showed that the inhibitory effect of sulfide to N2O reduction in mixed microbial communities is reversible and can be counteracted by dosing trace amounts of copper. It remained, however, unclear if this was due to copper sulfide precipitation or a retrofitting of the copper containing N2O-reductase (N2OR). The present study aimed to elucidate the mechanism of the restoration of sulfide-inhibited N2O reducing activity by metal addition to a pure Pseudomonas aeruginosa culture. This was done by using other metals (zinc, cobalt and iron) in comparison with copper. Zinc and cobalt clearly alleviated the sulfide inhibition of N2OR to the same extent as copper and the activity restoration was extremely fast (within 15 min, Fig. 3) for zinc, cobalt and copper. This suggests that the alleviation of the inhibitory effect of sulfide is due to metal sulfide precipitation and thus not exclusively limited to Cu. This work also underlines the importance of metal speciation: supply of iron did not restore the N2OR activity because it was precipitated by the phosphates present in the medium and thus could not precipitate the sulfide. 相似文献
127.
128.
CD4+CD28null T cells in autoimmune disease: pathogenic features and decreased susceptibility to immunoregulation 总被引:1,自引:0,他引:1
Thewissen M Somers V Hellings N Fraussen J Damoiseaux J Stinissen P 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):6514-6523
To determine the role of expanded CD4(+)CD28(null) T cells in multiple sclerosis and rheumatoid arthritis pathology, these cells were phenotypically characterized and their Ag reactivity was studied. FACS analysis confirmed that CD4(+)CD28(null) T cells are terminally differentiated effector memory cells. In addition, they express phenotypic markers that indicate their capacity to infiltrate into tissues and cause tissue damage. Whereas no reactivity to the candidate autoantigens myelin basic protein and collagen type II was observed within the CD4(+)CD28(null) T cell subset, CMV reactivity was prominent in four of four HC, four of four rheumatoid arthritis patients, and three of four multiple sclerosis patients. The level of the CMV-induced proliferative response was found to be related to the clonal diversity of the response. Interestingly, our results illustrate that CD4(+)CD28(null) T cells are not susceptible to the suppressive actions of CD4(+)CD25(+) regulatory T cells. In conclusion, this study provides several indications for a role of CD4(+)CD28(null) T cells in autoimmune pathology. CD4(+)CD28(null) T cells display pathogenic features, fill up immunological space, and are less susceptible to regulatory mechanisms. However, based on their low reactivity to the autoantigens tested in this study, CD4(+)CD28(null) T cells most likely do not play a direct autoaggressive role in autoimmune disease. 相似文献
129.
Dumont D Noben JP Moreels M Vanderlocht J Hellings N Vandenabeele F Lambrichts I Stinissen P Robben J 《Journal of neurochemistry》2007,102(2):562-576
Oligodendrocytes are glial cells responsible for the synthesis and maintenance of myelin in the central nervous system (CNS). Oligodendrocytes are vulnerable to damage occurring in a variety of neurological diseases. Understanding oligodendrocyte biology is crucial for the dissemination of de- and remyelination mechanisms. The goal of the present study is the construction of a protein database of mature rat oligodendrocytes. Post-mitotic oligodendrocytes were isolated from mature Wistar rats and subjected to immunocytochemistry. Proteins were extracted and analyzed by means of two-dimensional gel electrophoresis and two-dimensional liquid chromatography, both coupled to mass spectrometry. The combination of the gel-based and gel-free approach resulted in confident identification of a total of 200 proteins. A minority of proteins were identified in both proteomic strategies. The identified proteins represent a variety of functional groups, including novel oligodendrocyte proteins. The results of this study emphasize the power of the applied proteomic strategy to study known or to reveal new proteins and to investigate their regulation in oligodendrocytes in different disease models. 相似文献
130.
The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase 下载免费PDF全文
Yu Z Genest PA ter Riet B Sweeney K DiPaolo C Kieft R Christodoulou E Perrakis A Simmons JM Hausinger RP van Luenen HG Rigden DJ Sabatini R Borst P 《Nucleic acids research》2007,35(7):2107-2115
Trypanosomatids contain an unusual DNA base J (beta-d-glucosylhydroxymethyluracil), which replaces a fraction of thymine in telomeric and other DNA repeats. To determine the function of base J, we have searched for enzymes that catalyze J biosynthesis. We present evidence that a protein that binds to J in DNA, the J-binding protein 1 (JBP1), may also catalyze the first step in J biosynthesis, the conversion of thymine in DNA into hydroxymethyluracil. We show that JBP1 belongs to the family of Fe(2+) and 2-oxoglutarate-dependent dioxygenases and that replacement of conserved residues putatively involved in Fe(2+) and 2-oxoglutarate-binding inactivates the ability of JBP1 to contribute to J synthesis without affecting its ability to bind to J-DNA. We propose that JBP1 is a thymidine hydroxylase responsible for the local amplification of J inserted by JBP2, another putative thymidine hydroxylase. 相似文献