888 resultados para Ethnographic and Theological Analysis
Resumo:
Topic: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME).
Clinical Relevance: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been reported as a risk factor for its development. A systematic review with a meta-analysis was undertaken to examine the evidence of an association between dyslipidemia and DME.
Methods: We defined eligibility criteria as randomized controlled trials (RCTs) and cohort, case-control, and cross-sectional studies reporting on the relationship between blood lipid levels and DME. We performed a literature search in MEDLINE, PubMed, and Embase from inception to September 2014. We used the NewcastleeOttawa scale to assess the quality of case-control, cross-sectional, and cohort studies, and the Cochrane risk of bias tool for RCTs.
Results: The search strategy identified 4959 publications. After screening, we selected 21 articles for review (5 cross-sectional, 5 cohort, 7 case-control, and 4 RCTs). Meta-analysis of case-control studies revealed that mean levels of total serum cholesterol (TC), low-density lipoproteins (LDLs), and serum triglycerides (TGs) were significantly higher in patients with DME compared with those without DME (TC: 30.08; 95% confidence interval [CI], 21.14e39.02; P < 0.001; LDL: 18.62; 95% CI, 5.80e31.43; P < 0.05; TG: 24.82; 95% CI, 9.21e40.42; P < 0.05). Meta-analysis of RCTs did not show significant risk in worsening of hard exudates and severity of DME in the lipid-lowering group compared with placebo (hard exudates: relative risk, 1.00; 95% CI, 0.47e2.11; P ¼ 1.00; DME: relative risk, 1.18; 95% CI, 0.75e1.86; P ¼ 0.48).
Conclusions: Despite evidence from the cohort studies and meta-analysis of the case-control studies suggesting a strong relationship between lipid levels and DME, this was not confirmed by the meta-analysis that included only prospective RCTs. Therefore, given the significant public health relevance of the topic, the relationship between lipid levels and DME deserves further investigation.
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OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.
METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.
RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.
CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.
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Vitamin D has been associated with reduced risk of many cancers, but evidence for oesophageal cancer is mixed. To clarify the role of Vitamin D, we performed a systematic review and meta-analysis to evaluate the association of Vitamin D exposures and oesophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's oesophagus and squamous dysplasia. Ovid MEDLINE, EMBASE and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D (n=3), Vitamin D intake (n=4), UVB exposure (n=1), and genetic factors (n=7) were retrieved. Higher 25-OHD was associated with increased risk of cancer (adenocarcinoma or SCC, OR=1.39;95%CI:1.04-1.74), with the majority of participants coming from China. No association was observed between Vitamin D intake and risk of cancer overall (OR=1.03;0.65-1.42); however, a non-significantly increased risk for adenocarcinoma (OR=1.45;0.65-2.24) and non-significantly decreased risk for SCC (OR=0.80;0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers, OR=0.45;0.00-0.91, and a suggestive association was observed for rs2107301. No consistent associations were observed between Vitamin D exposures and occurrence of oesophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made.
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Background
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.
Methods
We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate.
Discussion
While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials.
Systematic review registration
PROSPERO CRD42013005608. (http://www.crd.york.ac.uk/PROSPERO/)
Resumo:
Purpose: We conducted a systematic review and meta-analysis of observational studies to evaluate the effect of oral statins on intraocular pressure (IOP) and the incidence and progression of glaucoma. Methods: This was a systematic review of the literature and meta-analysis. Searches of PubMed/Medline and Embase were conducted to include all types of studies. Gray literature abstracts were also considered for inclusion. Last search date was February 2016. Risk of bias was assessed using the Newcastle-Ottawa scale independently by two reviewers. Odds ratios (OR) or hazard ratios (HR) and 95% confidence intervals (CI) were extracted from each study. Pooled ORs for incidence of glaucoma were calculated using a random-effects model. Results: We identified seven cohort studies, three case–control studies, and one cross-sectional study with a total number of 583,615 participants. No randomized controlled trials were retrieved. Pooled ORs demonstrated a statistically significant association between short-term statin use (≤2 years) and reduced incidence of glaucoma (OR 0.96, 95%CI 0.94, 0.99). Pooled ORs of long-term statin use (>2 years) did not demonstrate statistically significant reduction in incidence of glaucoma (OR 0.70, 95%CI 0.46, 1.06). There was inconsistent evidence for the protective effect of statins against the progression of glaucoma, although there was no standard definition for progression across studies. There was no significant difference in IOP associated with statin use. Conclusions: Short-term statin use is associated with a reduced incidence of glaucoma. The effect of statins on glaucoma progression and IOP is uncertain.
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BACKGROUND: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT). METHODS: Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference. RESULTS: Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40 years, pooled HR 0.30 (95% CI 0.11-0.82). CONCLUSIONS: Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients.
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Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.
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Tese de dout., Filosofia, Department of Management Science, University of Strathclyde, 2004
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Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor β (TGFβ) superfamily with a central role in bone formation and mineralization. BMP2, a founding member of this family, has demonstrated remarkable osteogenic properties and is clinically used to promote bone repair and fracture healing. Lack of basic data on factors regulating BMP2 expression and activity have hampered a better understanding of its role in bone formation and bone-related diseases. The objective of this work was to collect new functional data and determine spatiotemporal expression patterns in a fish system aiming towards a better understanding of BMP2 function and regulation. Transcriptional and post-transcriptional regulation of gilthead seabream BMP2 gene was inferred from luciferase reporter systems. Several bone- and cartilage-related transcription factors (e.g. RUNX3, MEF2c, SOX9 and ETS1) were found to regulate BMP2 transcription, while microRNA 20a was shown to affect stability of the BMP2 transcript and thus the mineralogenic capacity of fish bone-derived host cells. The regulation of BMP2 activity through an interaction with the matrix Gla protein (MGP) was investigated in vitro using BMP responsive elements (BRE) coupled to luciferase reporter gene. Although we demonstrated the functionality of the experimental system in a fish cell line and the activation of BMP signaling pathway by seabream BMP2, no conclusive evidence could be collected on a possible interaction beween MGP and BMP2. The evolutionary relationship among the members of BMP2/4/16 subfamily was inferred from taxonomic and phylogenetic analyses. BMP16 diverged prior to BMP2 and BMP4 and should be the result of an ancient genome duplication that occurred early in vertebrate evolution. Structural and functional data suggested that all three proteins are effectors of the BMP signaling pathway, but expression data revealed different spatiotemporal patterns in teleost fish suggesting distinct mechanisms of regulation. In this work, through the collection of novel data, we provide additional insight into the regulation, the structure and the phylogenetic relationship of BMP2 and its closely related family members.
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Tese de doutoramento, Ciências Biomédicas, Universidade do Algarve, Departamento de Ciências Biomédicas e Medicina, 2014
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La réponse mécanique d’une cellule à une force externe permet d’inférer sa structure et fonction. Les pinces optiques s’avèrent une approche particulièrement attrayante pour la manipulation et caractérisation biophysique sophistiquée des cellules de façon non invasive. Cette thèse explore l’utilisation de trois types de pinces optiques couramment utilisées : 1) statiques (static), 2) à exposition partagée (time-sharing) et 3) oscillantes (oscillating). L’utilisation d’un code basé sur la méthode des éléments finis en trois dimensions (3DFEM) nous permet de modéliser ces trois types de piégeage optique afin d’extraire les propriétés mécaniques cellulaires à partir des expériences. La combinaison des pinces optiques avec la mécanique des cellules requiert des compétences interdisciplinaires. Une revue des approches expérimentales sur le piégeage optique et les tests unicellulaires est présentée. Les bases théoriques liant l’interaction entre la force radiative optique et la réponse mécanique de la cellule aussi. Pour la première fois, une simulation adaptée (3DFEM) incluant la diffusion lumineuse et la distribution du stress radiatif permet de prédire la déformation d’une cellule biconcave –analogue aux globules rouges—dans un piège statique double (static dual-trap). À l’équilibre, on observe que la déformation finale est donnée par l’espacement entre les deux faisceaux lasers: la cellule peut être étirée ou même comprimée. L’exposition partagée (time-sharing) est la technique qui permet de maintenir plusieurs sites de piégeage simultanément à partir du même faisceau laser. Notre analyse quantitative montre que, même oscillantes, la force optique et la déformation sont omniprésentes dans la cellule : la déformation viscoélastique et la dissipation de l’énergie sont analysées. Une autre cellule-type, la tige cubique, est étudiée : cela nous permet d’élucider de nouvelles propriétés sur la symétrie de la réponse mécanique. Enfin, l’analyse de la déformation résolue en temps dans un piége statique ou à exposition partagée montre que la déformation dépend simultanément de la viscoélasticité, la force externe et sa forme tridimensionnelle. La technique à force oscillante (oscillating tweezers) montre toutefois un décalage temporel, entre la force et la déformation, indépendant de la forme 3D; cette approche donnerait directement accès au tenseur viscoélastique complexe de la cellule.
Resumo:
Master Thesis in Mechanical Engineering field of Maintenance and Production
