Two Cheers For Diversity: An Experimental Study Of Micro-level Heterogeneity In Problemistic Search

In this paper, we argue for an expanded view of problemistic search. Recent behavioral theory research suggests that individual search preferences influence problemistic search. We draw on this to challenge the view of problemistic search as a centrally directed organizational process that proceeds sequentially from local to distant search. We argue that search activities in organizations are heterogeneous – some individuals will first engage in local search while others may move directly to distant search. We propose that problemistic search at the macroorganizational level is therefore the result of a mix of local and distant search activities at the micro-level that shifts towards distant search in response to negative performance evaluation. We test this idea in a laboratory experiment using a repetitive task and performance feedback

Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle

Background BCG is the most widely used vaccine of all time and remains the only licensed vaccine for use against tuberculosis in humans. BCG also protects other species such as cattle against tuberculosis, but due to its incompatibility with current tuberculin testing regimens remains unlicensed. BCG’s efficacy relates to its ability to persist in the host for weeks, months or even years after vaccination. It is unclear to what degree this ability to resist the host’s immune system is maintained by a dynamic interaction between the vaccine strain and its host as is the case for pathogenic mycobacteria. Results To investigate this question, we constructed transposon mutant libraries in both BCG Pasteur and BCG Danish strains and inoculated them into bovine lymph nodes. Cattle are well suited to such an assay, as they are naturally susceptible to tuberculosis and are one of the few animal species for which a BCG vaccination program has been proposed. After three weeks, the BCG were recovered and the input and output libraries compared to identify mutants with in vivo fitness defects. Less than 10% of the mutated genes were identified as affecting in vivo fitness, they included genes encoding known mycobacterial virulence functions such as mycobactin synthesis, sugar transport, reductive sulphate assimilation, PDIM synthesis and cholesterol metabolism. Many other attenuating genes had not previously been recognised as having a virulence phenotype. To test these genes, we generated and characterised three knockout mutants that were predicted by transposon mutagenesis to be attenuating in vivo: pyruvate carboxylase, a hypothetical protein (BCG_1063), and a putative cyclopropane-fatty-acyl-phospholipid synthase. The knockout strains survived as well as wild type during in vitro culture and in bovine macrophages, yet demonstrated marked attenuation during passage in bovine lymph nodes confirming that they were indeed involved in persistence of BCG in the host. Conclusion These data show that BCG is far from passive during its interaction with the host, rather it continues to employ its remaining virulence factors, to interact with the host’s innate immune system to allow it to persist, a property that is important for its protective efficacy.</p

How do supply- and demand-side interventions influence equity in healthcare utilisation? Evidence from maternal healthcare in Senegal

The launch of the Millennium Development Goals in 2000, followed by the Sustainable Development Goals in 2015, and the increasing focus on achieving universal health coverage has led to numerous interventions on both supply- and demand-sides of health systems in low- and middle-income countries. While tremendous progress has been achieved, inequities in access to healthcare persist, leading to calls for a closer examination of the equity implications of these interventions. This paper examines the equity implications of two such interventions in the context of maternal healthcare in Senegal. The first intervention on the supply-side focuses on improving the availability of maternal health services while the second intervention, on the demand-side, abolished user fees for facility deliveries. Using three rounds of Demographic Health Surveys covering the period 1992 to 2010 and employing three measures of socioeconomic status (SES) based on household wealth, mothers' education and rural/urban residence – we find that although both interventions increase utilisation of maternal health services, the rich benefit more from the supply-side intervention, thereby increasing inequity, while the poor benefit more from the demand-side intervention i.e. reducing inequity. Both interventions positively influence facility deliveries in rural areas although the increase in facility deliveries after the demand-side intervention is more than the increase after the supply-side intervention. There is no significant difference in utilisation based on mothers’ education. Since people from different SES categories are likely to respond differently to interventions on the supply- and demand-side of the health system, policymakers involved in the design of health programmes should pay closer attention to concerns of inequity and elite capture that may unintentionally result from these interventions

Secreted Osteopontin Is Highly Polymerized in Human Airways and Fragmented in Asthmatic Airway Secretions

BACKGROUND: Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma. METHODOLOGY: To determine whether secreted OPN (sOPN) is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL) fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects). All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation. PRINCIPAL FINDINGS: We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects. CONCLUSIONS: These results suggest that sOPN in human airways (1) undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2) is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3) may contribute to recruitment or survival of alveolar macrophages