Evaluation of bias in HIV seroprevalence estimates from national household surveys

Submitted by Gilvan Almeida ([email protected]) on 2016-12-07T12:03:30Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5)Rejected by Éder Freyre ([email protected]), reason: Refazer on 2017-02-14T16:35:23Z (GMT)Submitted by Gilvan Almeida ([email protected]) on 2019-02-06T16:28:18Z No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Regiane Silva ([email protected]) on 2019-08-26T13:12:58Z (GMT) No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-08-26T13:12:58Z (GMT). No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008Fundação Alfredo da Matta. Manaus, AM, Brasil.London School of Hygiene & Tropical Medicine. London, UK.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.World Health Organization. Geneva, Switzerland.OBJECTIVES: To assess the performance, usefulness and cost of a rapid treponemal antibody assay (VisiTect Syphilis) to detect syphilis in high risk populations. METHODS: People who attended STI clinics in Manaus, Brazil, were screened for syphilis using the fluorescent treponemal antibody absorption (FTA-Abs) test and a non-treponemal test (Venereal Diseases Research Laboratory (VDRL)), and for HIV. Finger prick blood samples were tested with VisiTect Syphilis. The rapid test was evaluated against the reference FTA-Abs and for its usefulness in detecting active syphilis (FTA-Abs and VDRL positive). Operational performance was assessed through providers' and patients' interviews. An economic evaluation was conducted from the provider's perspective. RESULTS: 510 patients (60% men) were enrolled, of whom 13 (2.5%) were HIV-1 seropositive. Syphilis prevalence (FTA-Abs) was 18% and active syphilis prevalence was 7.5%. 11% (57/506) of samples were positive by VisiTect. The sensitivity, specificity, positive and negative predictive values of VisiTect Syphilis were 57% (95% CI 45.8 to 66.7), 99% (95% CI 97.0 to 99.6), 91% (95% CI 80.0 to 96.7) and 91% (95% CI 88.0 to 93.5), respectively. VisiTect Syphilis identified 79% (30/38) of active syphilis cases. The cost per case of syphilis was $16.8 for VDRL,$33.2 for low cost and $56.3 for high cost VisiTect Syphilis; the cost per case of active syphilis was$21.3, $57.5 and$97.6, respectively. Patients identified finger prick pain and preference for venous blood collection as minor barriers to test use. CONCLUSION: VisiTect Syphilis had low sensitivity in field use and was less cost effective than conventional VDRL. However, rapid and correct identification of a high proportion of active syphilis cases combined with operational characteristics suggest a role in high risk populations

Sparse classification with MRI based markers for neuromuscular disease categorization

International audienceIn this paper, we present a novel method for disease classification between two patient populations based on features extracted from Magnetic Resonance Imaging (MRI) data. Anatomically meaningful features are extracted from structural data (T1- and T2-weighted MR images) and Diffusion Tensor Imaging (DTI) data, and used to train a new machine learning algorithm, the k-support SVM (ksup-SVM). The k-support regularized SVM has an inherent feature selection property, and thus it eliminates the requirement for a separate feature selection step. Our dataset consists of patients that suffer from facioscapulohumeral muscular dystrophy (FSH) and Myotonic muscular dystrophy type 1 (DM1) and our proposed method achieves a high performance. More specifically, it achieves a mean Area Under the Curve (AUC) of 0.7141 and mean accuracy 77% ± 0.013. Moreover, we provide a sparsity visualization of the features in order to indentify their discriminative value. The results suggest the potential of the combined use of MR markers to diagnose myopathies, and the general utility of the ksup-SVM. Source code is also available at https://gitorious.org/ksup-svm

Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia

Muscle protein degradation is thought to play a major role in muscle atrophy in cancer cachexia. To investigate the importance of the ubiquitin-proteasome pathway, which has been suggested to be the main degradative pathway mediating progressive protein loss in cachexia, the expression of mRNA for proteasome subunits C2 and C5 as well as the ubiquitin-conjugating enzyme, E214k, has been determined in gastrocnemius and pectoral muscles of mice bearing the MAC16 adenocarcinoma, using competitive quantitative reverse transcriptase polymerase chain reaction. Protein levels of proteasome subunits and E214k were determined by immunoblotting, to ensure changes in mRNA were reflected in changes in protein expression. Muscle weights correlated linearly with weight loss during the course of the study. There was a good correlation between expression of C2 and E214k mRNA and protein levels in gastrocnemius muscle with increases of 6–8-fold for C2 and two-fold for E214k between 12 and 20% weight loss, followed by a decrease in expression at weight losses of 25–27%, although loss of muscle protein continued. In contrast, expression of C5 mRNA only increased two-fold and was elevated similarly at all weight losses between 7.5 and 27%. Both proteasome functional activity, and proteasome-specific tyrosine release as a measure of total protein degradation was also maximal at 18–20% weight loss and decreased at higher weight loss. Proteasome expression in pectoral muscle followed a different pattern with increases in C2 and C5 and E214k mRNA only being seen at weight losses above 17%, although muscle loss increased progressively with increasing weight loss. These results suggest that activation of the ubiquitin-proteasome pathway plays a major role in protein loss in gastrocnemius muscle, up to 20% weight loss, but that other factors such as depression in protein synthesis may play a more important role at higher weight loss

Analysis and Prediction of Translation Rate Based on Sequence and Functional Features of the mRNA

Protein concentrations depend not only on the mRNA level, but also on the translation rate and the degradation rate. Prediction of mRNA's translation rate would provide valuable information for in-depth understanding of the translation mechanism and dynamic proteome. In this study, we developed a new computational model to predict the translation rate, featured by (1) integrating various sequence-derived and functional features, (2) applying the maximum relevance & minimum redundancy method and incremental feature selection to select features to optimize the prediction model, and (3) being able to predict the translation rate of RNA into high or low translation rate category. The prediction accuracies under rich and starvation condition were 68.8% and 70.0%, respectively, evaluated by jackknife cross-validation. It was found that the following features were correlated with translation rate: codon usage frequency, some gene ontology enrichment scores, number of RNA binding proteins known to bind its mRNA product, coding sequence length, protein abundance and 5′UTR free energy. These findings might provide useful information for understanding the mechanisms of translation and dynamic proteome. Our translation rate prediction model might become a high throughput tool for annotating the translation rate of mRNAs in large-scale

Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Nutritional supplementation of omega-3 fatty acids has been proposed to modulate the balance of pro- and anti-inflammatory mediators in sepsis. If proved to improve clinical outcomes in critically ill patients with sepsis, this intervention would be easy to implement. However, the cumulative evidence from several randomized clinical trials (RCTs) remains unclear. METHODS: We searched the Cochrane Library, MEDLINE, and EMBASE through December 2016 for RCTs on parenteral or enteral omega-3 supplementation in adult critically ill patients diagnosed with sepsis or septic shock. We analysed the included studies for mortality, intensive care unit (ICU) length of stay, and duration of mechanical ventilation, and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the quality of the evidence for each outcome. RESULTS: A total of 17 RCTs enrolling 1239 patients met our inclusion criteria. Omega-3 supplementation compared to no supplementation or placebo had no significant effect on mortality [relative risk (RR) 0.85; 95% confidence interval (CI) 0.71, 1.03; P = 0.10; I (2) = 0%; moderate quality], but significantly reduced ICU length of stay [mean difference (MD) -3.79 days; 95% CI -5.49, -2.09; P < 0.0001, I (2) = 82%; very low quality] and duration of mechanical ventilation (MD -2.27 days; 95% CI -4.27, -0.27; P = 0.03, I (2) = 60%; very low quality). However, sensitivity analyses challenged the robustness of these results. CONCLUSION: Omega-3 nutritional supplementation may reduce ICU length of stay and duration of mechanical ventilation without significantly affecting mortality, but the very low quality of overall evidence is insufficient to justify the routine use of omega-3 fatty acids in the management of sepsis

Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.published_or_final_versio

DW-MRI as a Biomarker to Compare Therapeutic Outcomes in Radiotherapy Regimens Incorporating Temozolomide or Gemcitabine in Glioblastoma

The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

<p>Abstract</p> <p>Background</p> <p>The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).</p> <p>Methods</p> <p>The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.</p> <p>Results</p> <p>We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, <it>CD9 </it>and <it>CALM2 </it>mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.</p> <p>Conclusion</p> <p>This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.</p