711 research outputs found

    Parental Acceptance of HPV Vaccine in Peru: A Decision Framework

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    En: Plos ONE, Vol. 7, No. 10, e48017. doi:10.1371/journal.pone.0048017Objective and Method: Cervical cancer is the third most common cancer affecting women worldwide and it is an important cause of death, especially in developing countries. Cervical cancer is caused by human papillomavirus (HPV) and can be prevented by HPV vaccine. The challenge is to expand vaccine availability to countries where it is most needed. In 2008 Peru’s Ministry of Health implemented a demonstration project involving 5th grade girls in primary schools in the Piura region. We designed and conducted a qualitative study of the decision-making process among parents of girls, and developed a conceptual model describing the process of HPV vaccine acceptance. Results: We found a nonlinear HPV decision-making process that evolved over time. Initially, the vaccine’s newness, the requirement of written consent, and provision of information were important. If information was sufficient and provided by credible sources, many parents accepted the vaccine. Later, after obtaining additional information from teachers, health personnel, and other trusted sources, more parents accepted vaccination. An understanding of the issues surrounding the vaccine developed, parents overcome fears and rumors, and engaged in family negotiations–including hearing the girl’s voice in the decision-making process. The concept of prevention (cancer as danger, future health, and trust in vaccines) combined with pragmatic factors (no cost, available at school) and the credibility of the offer (information in the media, recommendation of respected authority figure) were central to motivations that led parents to decide to vaccinate their daughters. A lack of confidence in the health system was the primary inhibitor of vaccine acceptance. Conclusions: Health personnel and teachers are credible sources of information and can provide important support to HPV vaccination campaigns

    A hazardous substance exposure prevention rating method for intervention needs assessment and effectiveness evaluation: the Small Business Exposure Index

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    Aims This paper describes the refinement and adaptation to small business of a previously developed method for systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing worksites, and evaluating intervention effectiveness. Methods We developed a checklist containing six unique sets of yes/no variables organized in a 2 × 3 matrix of exposure potential versus exposure protection at three levels corresponding to a simplified hierarchy of controls: materials, processes, and human interface. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate an exposure prevention \u27Small Business Exposure Index\u27 (SBEI) Summary score for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist administered by an industrial hygienist during walk-through inspection (N = 149 manufacturing processes/areas in 25 small to medium-sized manufacturing worksites). One area or process per manufacturing department was assessed and rated. A second hygienist independently assessed 36 areas to evaluate inter-rater reliability. Results The SBEI Summary scores indicated that exposures were well controlled in the majority of areas assessed (58% with rating of 1 or 2 on a 6-point scale), that there was some room for improvement in roughly one-third of areas (31% of areas rated 3 or 4), and that roughly 10% of the areas assessed were urgently in need of intervention (rated as 5 or 6). Inter-rater reliability of EP ratings was good to excellent (e.g., for SBEI Summary scores, weighted kappa = 0.73, 95% CI 0.52–0.93). Conclusion The SBEI exposure prevention rating method is suitable for use in small/medium enterprises, has good discriminatory power and reliability, offers an inexpensive method for intervention needs assessment and effectiveness evaluation, and complements quantitative exposure assessment with an upstream prevention focus

    A Gravitational Redshift Determination of the Mean Mass of White Dwarfs. DA Stars

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    We measure apparent velocities (v_app) of the Halpha and Hbeta Balmer line cores for 449 non-binary thin disk normal DA white dwarfs (WDs) using optical spectra taken for the ESO SN Ia Progenitor surveY (SPY; Napiwotzki et al. 2001). Assuming these WDs are nearby and co-moving, we correct our velocities to the Local Standard of Rest so that the remaining stellar motions are random. By averaging over the sample, we are left with the mean gravitational redshift, : we find = = 32.57 +/- 1.17 km/s. Using the mass-radius relation from evolutionary models, this translates to a mean mass of 0.647 +0.013 -0.014 Msun. We interpret this as the mean mass for all DAs. Our results are in agreement with previous gravitational redshift studies but are significantly higher than all previous spectroscopic determinations except the recent findings of Tremblay & Bergeron (2009). Since the gravitational redshift method is independent of surface gravity from atmosphere models, we investigate the mean mass of DAs with spectroscopic Teff both above and below 12000 K; fits to line profiles give a rapid increase in the mean mass with decreasing Teff. Our results are consistent with no significant change in mean mass: ^hot = 0.640 +/- 0.014 Msun and ^cool = 0.686 +0.035 -0.039 Msun.Comment: Accepted for publication in ApJ, 14 pages, 12 figure

    Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

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    Aims/hypothesis The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. Materials and methods NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. Results Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. Conclusions/interpreation The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity

    Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

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    BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for \u3e4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured

    Computational Biology in Costa Rica: The Role of a Small Country in the Global Context of Bioinformatics

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    Introduction: The successful development of high throughput methods for DNA sequencing, transcriptomics, proteomics, and other –omics, has contributed to the emergence of novel possibilities for the examination of complex biological systems through computational analysis. These fields have witnessed unprecedented advances in high income countries. Nevertheless, the role of other nations needs to be examined in order to delineate their contribution within the global context of bioinformatics. Previous articles have focused on the expansion of Computational Biology in Brazil and Mexico [1],[2], two of the largest Latin American countries, and which have shown political commitment to foster their scientific development. Costa Rica is a small Central American country with a population of 4 million, with its territory 164 and 38 times smaller than Brazil and Mexico, respectively. Thus, it is interesting to visualize the possibilities and challenges of this low-income country in the context of the global bioinformatics endeavor.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

    Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

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    Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context
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