Evidence and Policy in Aid-Dependent Settings

This chapter examines how the political dynamics of aid relationships can affect the use of evidence within health policymaking. Empirical examples from Cambodia, Ethiopia and Ghana illustrate how relationships between national governments and donor agencies influence the ways in which evidence is generated, selected, or utilised to inform policymaking. We particularly consider how relationships with donors influence the underlying systems and processes of evidence use. We find a number of issues affecting which bodies or forms of evidence are taken to be policy relevant, including: levels of local technical capacity to utilise or synthesise evidence; differing stakeholder framing of issues; and the influence of non-state actors on sector-wide systems of agenda setting. The chapter also reflects on some of the key governance implications of these arrangements in which global actors promote forms of evidence use – often under a banner of technical efficiency – with limited consideration for local representation or accountability

Syphilis epidemiology in Norway, 1992-2008: resurgence among men who have sex with men

<p>Abstract</p> <p>Background</p> <p>In recent years, the number of syphilis cases has stabilised in many countries of Western Europe, however several countries have reported increases among men who have sex with men (MSM). The aim of this article was to describe the epidemiology of early syphilis in Norway in 1992-2008.</p> <p>Methods</p> <p>Cases of early syphilis and congenital syphilis reported to the Norwegian Surveillance System for Communicable Diseases (MSIS) 1992-2008 were described by route of transmission, gender, age, birthplace, stage of disease, HIV co-infection, source partner and place of infection.</p> <p>Results</p> <p>The incidence of reported syphilis ranged from 0.05 (1992) to 1.50 (2002) per 100 000 person-years. Of 562 cases reported to MSIS during the study period, 62% were men infected by another man. The proportion of those, infected homosexually increased from 0 (1992-1994) to 77% (2008). Most of them were Norwegians (83%). The proportion of HIV co-infection among homosexually infected increased over time and reached 39% in 2008. The majority reported being infected by a casual partner (73%) and in the municipality of Oslo (72%). Of 152 heterosexually infected men 64% were Norwegians; 51% were infected by casual contacts and 20% by commercial sex workers; 73% were infected abroad. Among 56 women, 57% were Norwegians, 57% were infected by a steady partner and 40% were infected abroad. Almost half (46%) were diagnosed in the early latent stage. Four cases had congenital syphilis, two of whom were adopted from abroad.</p> <p>Conclusions</p> <p>Syphilis is rare in Norway, but MSM represent almost two thirds of cases. The increase of HIV co-infected cases among MSM may enhance transmission of both infections. We recommend sexually active MSM to be tested for syphilis 2-4 times a year. Due to its variable clinical course, syphilis might be difficult to recognise at an early stage among women in a low-prevalence population. We estimate current practice of prenatal screening in Norway as sufficient.</p

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

Rapid copper acquisition by developing murine mesothelioma: Decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration

Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an antiangiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes

Yeast IME2 Functions Early in Meiosis Upstream of Cell Cycle-Regulated SBF and MBF Targets

BACKGROUND: In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosis-specific protein kinase Ime2, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and facilitate initiation of DNA replication. While Ime2 is required for Sic1 destruction during meiosis, evidence now suggests that Ime2 does not directly catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do during the cell cycle. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Sic1 is eventually degraded in meiotic cells lacking the IME2 gene (ime2Δ), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2Δ cells. Analysis of these expression data has provided evidence that Ime2 is required early in meiosis for normal transcription of many genes that are also periodically expressed during late G1 of the cell cycle. CONCLUSIONS/SIGNIFICANCE: Our results place Ime2 at a position in the early meiotic pathway that lies upstream of the position occupied by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even further upstream in the corresponding meiotic cascade

On some generalizations of the properties of the multidimensional generalized Erdélyi-Kober operators and their applications

In this paper we investigate the composition of a multidimensional generalized Erdélyi-Kober operator with differential operators of high order. In particular, with powers of the differential Bessel operator. Applications of proved properties to solving the Cauchy problem for a multidimensional polycaloric equation with a Bessel operator are show

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

The many meanings of evidence: a comparative analysis of the forms and roles of evidence within three health policy processes in Cambodia

Background Discussions within the health community routinely emphasise the importance of evidence in informing policy formulation and implementation. Much of the support for the evidence-based policy movement draws from concern that policy decisions are often based on inadequate engagement with high-quality evidence. In many such discussions, evidence is treated as differing only in quality, and assumed to improve decisions if it can only be used more. In contrast, political science scholars have described this as an overly simplistic view of the policy-making process, noting that research ‘use’ can mean a variety of things and rely on nuanced aspects of political systems. An approach more in recognition of how policy-making systems operate in practice can be to consider how institutions and ideas influence which pieces of evidence appear to be relevant for, and are used within, different policy processes. Methods Drawing on in-depth interviews undertaken in 2015/16 with key health sector stakeholders in Cambodia, we investigate the evidence perceived to be relevant to policy decisions for three contrasting health policy examples – tobacco control, HIV/AIDS and performance-based salary incentives. These cases allow us to examine the ways that policy relevant evidence may differ given the framing of the issue and the broader institutional context in which evidence is considered. Results The three health issues show few similarities in how pieces of evidence were used in various aspects of policy-making, despite all being discussed within a broad policy environment in which evidence-based policymaking is rhetorically championed. Instead, we find that evidence use can be better understood by mapping how these health policy issues differ in terms of the issue characteristics, and also in terms of the stakeholders structurally established as having dominant influence for each issue. Both of these have important implications for evidence use. Contrasting concerns of key stakeholders meant that evidence related to differing issues could be understood in terms of how it was policy relevant. The stakeholders involved, however, could further be seen to possess differing logics about how to go about achieving their various outcomes – logics that could further help explain the differences seen in evidence utilisation. Conclusion A comparative approach reiterates that evidence is not a uniform concept for which more is obviously better, but rather illustrates how different constructions and pieces of evidence become relevant in relation to the features of specific health policy decisions. An institutional approach that considers the structural position of stakeholders with differing core goals or objectives, as well as their logics related to evidence utilisation, can further help to understand some of the complexities of evidence use in health policymaking

Priorities for synthesis research in ecology and environmental science

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science