Lost in Translation: Piloting a Novel Framework to Assess the Challenges in Translating Scientific Uncertainty From Empirical Findings to WHO Policy Statements.

BACKGROUND:Calls for evidence-informed public health policy, with implicit promises of greater program effectiveness, have intensified recently. The methods to produce such policies are not self-evident, requiring a conciliation of values and norms between policy-makers and evidence producers. In particular, the translation of uncertainty from empirical research findings, particularly issues of statistical variability and generalizability, is a persistent challenge because of the incremental nature of research and the iterative cycle of advancing knowledge and implementation. This paper aims to assess how the concept of uncertainty is considered and acknowledged in World Health Organization (WHO) policy recommendations and guidelines. METHODS:We selected four WHO policy statements published between 2008-2013 regarding maternal and child nutrient supplementation, infant feeding, heat action plans, and malaria control to represent topics with a spectrum of available evidence bases. Each of these four statements was analyzed using a novel framework to assess the treatment of statistical variability and generalizability. RESULTS:WHO currently provides substantial guidance on addressing statistical variability through GRADE (Grading of Recommendations Assessment, Development, and Evaluation) ratings for precision and consistency in their guideline documents. Accordingly, our analysis showed that policy-informing questions were addressed by systematic reviews and representations of statistical variability (eg, with numeric confidence intervals). In contrast, the presentation of contextual or "background" evidence regarding etiology or disease burden showed little consideration for this variability. Moreover, generalizability or "indirectness" was uniformly neglected, with little explicit consideration of study settings or subgroups. CONCLUSION:In this paper, we found that non-uniform treatment of statistical variability and generalizability factors that may contribute to uncertainty regarding recommendations were neglected, including the state of evidence informing background questions (prevalence, mechanisms, or burden or distributions of health problems) and little assessment of generalizability, alternate interventions, and additional outcomes not captured by systematic review. These other factors often form a basis for providing policy recommendations, particularly in the absence of a strong evidence base for intervention effects. Consequently, they should also be subject to stringent and systematic evaluation criteria. We suggest that more effort is needed to systematically acknowledge (1) when evidence is missing, conflicting, or equivocal, (2) what normative considerations were also employed, and (3) how additional evidence may be accrued

Managerial Valuation of Applicant Credentials and Personal Traits in Hiring Decisions

We study how managers value applicant credentials and personal traits in hiring decisions. Using the ordered probit model, we confirm previous results – managers rank applicant traits higher than credentials. However, we also uncover patterns not previously observed – managerial valuations of some of these characteristics are dependent on managers' perception of the overall state of the economy, on firm and immediate workplace characteristics, and on managers' personal characteristics. Manager valuations of credentials vary with a large number of factors; this is not so for applicant personal traits. This is not surprising as most managers view the five traits considered "as extremely important."personality, credentials, hiring practices, ordered probit

High-resolution 3D mapping of rhizosphere glycan patterning using molecular probes in a transparent soil system

Rhizospheres are microecological zones at the interface of roots and soils. Interactions between bacteria and roots are critical for maintaining plant and soil health but are difficult to study because of constraints inherent in working with underground systems. We have developed an in-situ rhizosphere imaging system based on transparent soils and molecular probes that can be imaged using confocal microscopy. We observed spatial patterning of polysaccharides along roots and on cells deposited into the rhizosphere and also co-localised fluorescently tagged soil bacteria. These studies provide insight into the complex glycan landscape of rhizospheres and suggest a means by which root / rhizobacteria interactions can be non-disruptively studied

Isolation and characterization of the full-length cDNA encoding a member of a novel cytochrome p450 family (CYP320A1) from the tropical freshwater snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni

Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins

Lost in Translation: Piloting a Novel Framework to Assess the Challenges in Translating Scientific Uncertainty From Empirical Findings to WHO Policy Statements

Background: Calls for evidence-informed public health policy, with implicit promises of greater program effectiveness, have intensified recently. The methods to produce such policies are not self-evident, requiring a conciliation of values and norms between policy-makers and evidence producers. In particular, the translation of uncertainty from empirical research findings, particularly issues of statistical variability and generalizability, is a persistent challenge because of the incremental nature of research and the iterative cycle of advancing knowledge and implementation. This paper aims to assess how the concept of uncertainty is considered and acknowledged in World Health Organization (WHO) policy recommendations and guidelines. Methods: We selected four WHO policy statements published between 2008-2013 regarding maternal and child nutrient supplementation, infant feeding, heat action plans, and malaria control to represent topics with a spectrum of available evidence bases. Each of these four statements was analyzed using a novel framework to assess the treatment of statistical variability and generalizability. Results: WHO currently provides substantial guidance on addressing statistical variability through GRADE (Grading of Recommendations Assessment, Development, and Evaluation) ratings for precision and consistency in their guideline documents. Accordingly, our analysis showed that policy-informing questions were addressed by systematic reviews and representations of statistical variability (eg, with numeric confidence intervals). In contrast, the presentation of contextual or “background” evidence regarding etiology or disease burden showed little consideration for this variability. Moreover, generalizability or “indirectness” was uniformly neglected, with little explicit consideration of study settings or subgroups. Conclusion: In this paper, we found that non-uniform treatment of statistical variability and generalizability factors that may contribute to uncertainty regarding recommendations were neglected, including the state of evidence informing background questions (prevalence, mechanisms, or burden or distributions of health problems) and little assessment of generalizability, alternate interventions, and additional outcomes not captured by systematic review. These other factors often form a basis for providing policy recommendations, particularly in the absence of a strong evidence base for intervention effects. Consequently, they should also be subject to stringent and systematic evaluation criteria. We suggest that more effort is needed to systematically acknowledge (1) when evidence is missing, conflicting, or equivocal, (2) what normative considerations were also employed, and (3) how additional evidence may be accrued

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma.

We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis

Mobile Authentication Assurance Statement (MAAS) Draft Specification

Authentication assurance is a statement of the level of protection that the authenticator enforces to assure that a user retains control of the credentials used in authentication. Protected secret credentials enable user authentication at high levels of assurance. This specification describes the format of a message for mobile assurance along with a healthcare provider use case, involving the user’s acquisition and operation of an app on a smartphone that uses the statement in an authentication protocol

Stakeholder narratives on trypanosomiasis, their effect on policy and the scope for One Health

Background This paper explores the framings of trypanosomiasis, a widespread and potentially fatal zoonotic disease transmitted by tsetse flies (Glossina species) affecting both humans and livestock. This is a country case study focusing on the political economy of knowledge in Zambia. It is a pertinent time to examine this issue as human population growth and other factors have led to migration into tsetse-inhabited areas with little historical influence from livestock. Disease transmission in new human-wildlife interfaces such as these is a greater risk, and opinions on the best way to manage this are deeply divided. Methods A qualitative case study method was used to examine the narratives on trypanosomiasis in the Zambian policy context through a series of key informant interviews. Interviewees included key actors from international organisations, research organisations and local activists from a variety of perspectives acknowledging the need to explore the relationships between the human, animal and environmental sectors. Principal Findings Diverse framings are held by key actors looking from, variously, the perspectives of wildlife and environmental protection, agricultural development, poverty alleviation, and veterinary and public health. From these viewpoints, four narratives about trypanosomiasis policy were identified, focused around four different beliefs: that trypanosomiasis is protecting the environment, is causing poverty, is not a major problem, and finally, that it is a Zambian rather than international issue to contend with. Within these narratives there are also conflicting views on the best control methods to use and different reasoning behind the pathways of response. These are based on apparently incompatible priorities of people, land, animals, the economy and the environment. The extent to which a One Health approach has been embraced and the potential usefulness of this as a way of reconciling the aims of these framings and narratives is considered throughout the paper. Conclusions/Significance While there has historically been a lack of One Health working in this context, the complex, interacting factors that impact the disease show the need for cross-sector, interdisciplinary decision making to stop rival narratives leading to competing actions. Additional recommendations include implementing: surveillance to assess under-reporting of disease and consequential under-estimation of disease risk; evidence-based decision making; increased and structurally managed funding across countries; and focus on interactions between disease drivers, disease incidence at the community level, and poverty and equity impacts