Individual and Contextual Factors Associated with Low Childhood Immunisation Coverage in Sub-Saharan Africa: A Multilevel Analysis

Background: In 2010, more than six million children in sub-Saharan Africa did not receive the full series of three doses of the diphtheria-tetanus-pertussis vaccine by one year of age. An evidence-based approach to addressing this burden of un-immunised children requires accurate knowledge of the underlying factors. We therefore developed and tested a model of childhood immunisation that includes individual, community and country-level characteristics. Method and Findings: We conducted multilevel logistic regression analysis of Demographic and Health Survey data for 27,094 children aged 12–23 months, nested within 8,546 communities from 24 countries in sub-Saharan Africa. According to the intra-country and intra-community correlation coefficient implied by the estimated intercept component variance, 21% and 32% of the variance in unimmunised children were attributable to country- and community-level factors respectively. Children born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to 1.40) with no formal education were more likely to be unimmunised than those born to parents with secondary or higher education. Children from the poorest households were 36% more likely to be unimmunised than counterparts from the richest households. Maternal access to media significantly reduced the odds of children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI 0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23), communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more likely to be unimmunised. Conclusion: We found that individual and contextual factors were associated with childhood immunisation, suggesting that public health programmes designed to improve coverage of childhood immunisation should address people, and the communities and societies in which they live

Informatics Technology Mimics Ecology: Dense, Mutualistic Collaboration Networks Are Associated with Higher Publication Rates

Information technology (IT) adoption enables biomedical research. Publications are an accepted measure of research output, and network models can describe the collaborative nature of publication. In particular, ecological networks can serve as analogies for publication and technology adoption. We constructed network models of adoption of bioinformatics programming languages and health IT (HIT) from the literature

Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants

The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9 in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12 months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5, and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that also uniquely induced cord blood IFNγ production. For most agonists, TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of age. TLR8 agonists also induced the greatest production of the Th1-polarizing cytokines TNFα and IFNγ throughout the first year of life, although the relative responses to the single TLR8 agonist and the combined TLR7/8 agonist changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most agonists were robust at birth and remained stable through 12 months of age. These observations provide fresh insights into the ontogeny of innate immunity in African children, and may inform development of age-specific adjuvanted vaccine formulations important for global health

Knowledge translation research in population health: establishing a collaborative research agenda

<p>Abstract</p> <p>Background</p> <p>Despite the increasing mobilization of researchers and funding organizations around knowledge translation (KT) in Canada and elsewhere, many questions have been only partially answered, particularly in the field of population health. This article presents the results of a systematic process to draw out possible avenues of collaboration for researchers, practitioners and decision-makers who work in the area of KT. The main objective was to establish a research agenda on knowledge translation in population health.</p> <p>Methods</p> <p>Using the Concept Mapping approach, the research team wanted to identify priority themes for the development of research on KT in population health. Mapping is based on multivariate statistical analyses (multidimensional scaling and hierarchical cluster analysis) in which statements produced during a brainstorming session are grouped in weighted clusters. The final maps are a visual representation of the priority themes of research on KT. Especially designed for facilitating consensus in the understanding and organization of various concepts, the Concept Mapping method proved suitable for achieving this objective.</p> <p>Results</p> <p>The maps were produced by 19 participants from university settings, and from institutions within the health and social services network. Three main perspectives emerge from this operation: (1) The evaluation of the effectiveness of KT efforts is one of the main research priorities; (2) The importance of taking into consideration user contexts in any KT effort; (3) The challenges related to sharing power for decision-making and action-taking among various stakeholder groups. These perspectives open up avenues of collaboration for stakeholders who are involved in research on KT. Besides these three main perspectives, the concept maps reveal three other trends which should be emphasized.</p> <p>Conclusion</p> <p>The Concept Mapping process reported in this article aimed to provoke collective reflection on the research questions that should be studied, in order to foster coherence in research activities in the field of population health. Based on this, it is appropriate to continue to support the development of research projects in KT and the formation of research teams in this field. Research on KT must lead to concrete outcomes within communities that are interested in the question.</p

Probing the Flexibility of Large Conformational Changes in Protein Structures through Local Perturbations

Protein conformational changes and dynamic behavior are fundamental for such processes as catalysis, regulation, and substrate recognition. Although protein dynamics have been successfully explored in computer simulation, there is an intermediate-scale of motions that has proven difficult to simulate—the motion of individual segments or domains that move independently of the body the protein. Here, we introduce a molecular-dynamics perturbation method, the Rotamerically Induced Perturbation (RIP), which can generate large, coherent motions of structural elements in picoseconds by applying large torsional perturbations to individual sidechains. Despite the large-scale motions, secondary structure elements remain intact without the need for applying backbone positional restraints. Owing to its computational efficiency, RIP can be applied to every residue in a protein, producing a global map of deformability. This map is remarkably sparse, with the dominant sites of deformation generally found on the protein surface. The global map can be used to identify loops and helices that are less tightly bound to the protein and thus are likely sites of dynamic modulation that may have important functional consequences. Additionally, they identify individual residues that have the potential to drive large-scale coherent conformational change. Applying RIP to two well-studied proteins, Dihdydrofolate Reductase and Triosephosphate Isomerase, which possess functionally-relevant mobile loops that fluctuate on the microsecond/millisecond timescale, the RIP deformation map identifies and recapitulates the flexibility of these elements. In contrast, the RIP deformation map of α-lytic protease, a kinetically stable protein, results in a map with no significant deformations. In the N-terminal domain of HSP90, the RIP deformation map clearly identifies the ligand-binding lid as a highly flexible region capable of large conformational changes. In the Estrogen Receptor ligand-binding domain, the RIP deformation map is quite sparse except for one large conformational change involving Helix-12, which is the structural element that allosterically links ligand binding to receptor activation. RIP analysis has the potential to discover sites of functional conformational changes and the linchpin residues critical in determining these conformational states

CMV Infection Attenuates the Disease Course in a Murine Model of Multiple Sclerosis

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies

Modelling innovative interventions for optimising healthy lifestyle promotion in primary health care: "Prescribe Vida Saludable" phase I research protocol

<p>Abstract</p> <p>Background</p> <p>The adoption of a healthy lifestyle, including physical activity, a balanced diet, a moderate alcohol consumption and abstinence from smoking, are associated with large decreases in the incidence and mortality rates for the most common chronic diseases. That is why primary health care (PHC) services are trying, so far with less success than desirable, to promote healthy lifestyles among patients. The objective of this study is to design and model, under a participative collaboration framework between clinicians and researchers, interventions that are feasible and sustainable for the promotion of healthy lifestyles in PHC.</p> <p>Methods and design</p> <p>Phase I formative research and a quasi-experimental evaluation of the modelling and planning process will be undertaken in eight primary care centres (PCCs) of the Basque Health Service – OSAKIDETZA, of which four centres will be assigned for convenience to the Intervention Group (the others being Controls). Twelve structured study, discussion and consensus sessions supported by reviews of the literature and relevant documents, will be undertaken throughout 12 months. The first four sessions, including a descriptive strategic needs assessment, will lead to the prioritisation of a health promotion aim in each centre. In the remaining eight sessions, collaborative design of intervention strategies, on the basis of a planning process and pilot trials, will be carried out. The impact of the formative process on the practice of healthy lifestyle promotion, attitude towards health promotion and other factors associated with the optimisation of preventive clinical practice will be assessed, through pre- and post-programme evaluations and comparisons of the indicators measured in professionals from the centres assigned to the Intervention or Control Groups.</p> <p>Discussion</p> <p>There are four necessary factors for the outcome to be successful and result in important changes: (1) the commitment of professional and community partners who are involved; (2) their competence for change; (3) the active cooperation and participation of the interdisciplinary partners involved throughout the process of change; and (4) the availability of resources necessary to facilitate the change.</p

Phenotypic Characterization of a Genetically Diverse Panel of Mice for Behavioral Despair and Anxiety

Animal models of human behavioral endophenotypes, such as the Tail Suspension Test (TST) and the Open Field assay (OF), have proven to be essential tools in revealing the genetics and mechanisms of psychiatric diseases. As in the human disorders they model, the measurements generated in these behavioral assays are significantly impacted by the genetic background of the animals tested. In order to better understand the strain-dependent phenotypic variability endemic to this type of work, and better inform future studies that rely on the data generated by these models, we phenotyped 33 inbred mouse strains for immobility in the TST, a mouse model of behavioral despair, and for activity in the OF, a model of general anxiety and locomotor activity.We identified significant strain-dependent differences in TST immobility, and in thigmotaxis and distance traveled in the OF. These results were replicable over multiple testing sessions and exhibited high heritability. We exploited the heritability of these behavioral traits by using in silico haplotype-based association mapping to identify candidate genes for regulating TST behavior. Two significant loci (-logp >7.0, gFWER adjusted p value <0.05) of approximately 300 kb each on MMU9 and MMU10 were identified. The MMU10 locus is syntenic to a major human depressive disorder QTL on human chromosome 12 and contains several genes that are expressed in brain regions associated with behavioral despair.We report the results of phenotyping a large panel of inbred mouse strains for depression and anxiety-associated behaviors. These results show significant, heritable strain-specific differences in behavior, and should prove to be a valuable resource for the behavioral and genetics communities. Additionally, we used haplotype mapping to identify several loci that may contain genes that regulate behavioral despair