Choosing the right databases and search techniques

This is the author accepted manuscript. The final version is available from Facet Publishing via the DOI in this recordIn this chapter we will explore how to choose resources and techniques to provide the best returns. Systematic searching is most often associated with systematic reviews in health care. However, systematic searching is also a key element of scoping reviews, systematic maps and realist reviews and the issues we describe here will certainly be useful when undertaking literature searching in any subject field including health, education and environment. By the end you will have confidence in how to plan for your search, how to select the best sources to search, and the best way to utilize those resources to maximize returns without increasing time pressures or workload. [...

Cost-effectiveness considerations in finding appropriate chemotherapy treatments for bacterial diseases in developing countries: The case of tuberculosis.

Infectious bacterial diseases in developing countries represent a major health threat. Living conditions and environment decrease health status such that those in developing countries are left vulnerable to many diseases that are seldom seen in industrialised countries. Many treatments for these diseases have proven very effective, making infectious bacterial disease one of the best targets for high yield, low cost health interventions. Antibiotics remain the primary approach in treating infectious bacterial disease, yet mismanagement in their use has led to unnecessary resistance making many major diseases difficult to treat. Additionally, poor antibiotic choices for treating diseases have further contributed to unnecessary resistance. The appropriate choice for treating diseases is not always made and many diseases continue to be treated with inappropriate drugs or combinations of drugs. Many treatments are chosen on the basis of their easy availability or their small cost, when in fact other treatments could be obtained that have a more substantial impact on decreasing the incidence of a given disease. This is especially true in the treatment of tuberculosis. Tuberculosis, once thought to have been almost eradicated, has been revived by the growth of HTV. TB still claims a substantial proportion of human lives and will be responsible for 30 million deaths in this decade alone. Of particular relevance is the rising incidence of drug resistant cases of TB, which is primarily due to inappropriate antibiotic use. Although some past research has acknowledged the influence of resistance on the cost of TB treatment in developing countries, few studies have thoroughly analysed this relationship. This thesis presents a comprehensive study of the impact of drug resistance on the cost of TB treatment within the context of a cost-effectiveness analysis comparing short-course chemotherapy and the standard drug regimen in Ethiopia. In addition, the impact of HIV on TB treatment is analysed together with other factors, such as case holding, in order to assess their respective influence on the cost of treatment. Criteria for better management of tuberculosis control efforts in order to eradicate this disease and control resistance are subsequently explored. Finally, a discussion of the broader applicability of the conclusions of these studies to many developing countries is presented

The reaction mechanism of metallo-beta-lactamases is tuned by the conformation of an active site mobile loop

Carbapenems are "last resort" β-lactam antibiotics used to treat serious and life-threatening health care-associated infections caused by multidrug-resistant Gram-negative bacteria. Unfortunately, the worldwide spread of genes coding for carbapenemases among these bacteria is threatening these life-saving drugs. Metallo-β-lactamases (MβLs) are the largest family of carbapenemases. These are Zn(II)-dependent hydrolases that are active against almost all β-lactam antibiotics. Their catalytic mechanism and the features driving substrate specificity have been matter of intense debate. The active sites of MβLs are flanked by two loops, one of which, loop L3, was shown to adopt different conformations upon substrate or inhibitor binding, and thus are expected to play a role in substrate recognition. However, the sequence heterogeneity observed in this loop in different MβLs has limited the generalizations about its role. Here, we report the engineering of different loops within the scaffold of the clinically relevant carbapenemase NDM-1. We found that the loop sequence dictates its conformation in the unbound form of the enzyme, eliciting different degrees of active-site exposure. However, these structural changes have a minor impact on the substrate profile. Instead, we report that the loop conformation determines the protonation rate of key reaction intermediates accumulated during the hydrolysis of different β-lactams in all MβLs. This study demonstrates the existence of a direct link between the conformation of this loop and the mechanistic features of the enzyme, bringing to light an unexplored function of active-site loops on MβLs.Fil: Palacios, Antonela Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mojica, María F.. Case Western Reserve University; Estados UnidosFil: Giannini, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Taracila, Magdalena A.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Bethel, Christopher R.. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Alzari, Pedro M.. Institut Pasteur de Paris; FranciaFil: Otero, Lisandro Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

The Chernobyl Tissue Bank - A Repository for Biomaterial and Data Used in Integrative and Systems Biology Modeling the Human Response to Radiation

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era

Deploying Web-based Visual Exploration Tools on the Grid

We discuss a web-based portal for the exploration, encapsulation, and dissemination of visualization results over the Grid. This portal integrates three components: an interface client for structured visualization exploration, a visualization web application to manage the generation and capture of the visualization results, and a centralized portal application server to access and manage grid resources. Our approach uses standard web technologies to make the system accessible with minimal user setup. We demonstrate the usefulness of the developed system using an example for Adaptive Mesh Refinement (AMR) data visualization