The utilisation of health research in policy-making: Concepts, examples, and methods of assessment

Chapter 1: Introduction and Background • The importance of utilising health research in policy-making, and therefore the need to understand the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. • For at least twenty years there has been recognition of the multiple meanings or models of research utilisation in policy-making. It has similarly been long recognised that a range of factors is involved in the interactions between health research and policy-makers. • The emerging focus on Health Research Systems (HRS) has identified additional mechanisms through which greater utilisation of research could be achieved. Assessment of the role of health research in policy-making is best undertaken as part of a wider study that also includes the utilisation of health research by industry, medical practitioners, and the public. Chapter 2: The Nature of Policy-Making, Types of Research and Utilisation Models • Policy-making broadly interpreted includes national health policies made by government ministers and officials, policies made by local health service managers, and clinical guidelines from professional bodies. In this report, however, the main focus is on public policy-making rather than that conducted by professional bodies. The utilisation of health research in policy-making should eventually lead to desired outcomes, including health gains. Research can make a contribution in at least three phases of the policy-making process: agenda setting; policy formulation; and implementation. Descriptions of these processes, however, can over-estimate the degree of rationality in policy-making. Therefore, the analysis is informed by a review of the full range of policy-making models. These include rational and incrementalist models. • Various categories of research are likely to be used differently in health policy-making. Applied research might be more readily useable by a policy system than basic research, but health policy-makers tend to relate more willingly to natural sciences than social sciences. When research is based on the priorities of potential users, and/or is research of proven quality, this increases the possibility that it will be translated into policies. There also appears to be a greater chance of research being used in clinical policies about delivering care to patients, than in national policies on the structures of the health service. • Models of research utilisation in policy-making start with a link to rational or instrumental views of policy-making, and include descriptions of how commissioned research can help to find solutions to problems. Other models relate to an incrementalist view in which policy-making involves a series of small steps over a long period; research findings might gradually cause a shift in perceptions about an issue in a process of ‘enlightenment’. Interactive models of research utilisation stress the way in which policy-makers and researchers might develop links over a long period. Research can also be used symbolically to support decisions already taken. Chapter 3: Examples from Previous Studies • A study of health policy-making in two southern African countries illustrates how policy-making processes can be analysed. It addresses agenda setting, policy formulation and implementation. The methods used included documentary analysis and key informant interviews. • Many previous studies of research utilisation can provide lessons for future assessments. Two broad approaches can be identified. Some studies start with pieces, or programmes, of research and examine their impact. Others consider policy on a particular topic and assess the role of research in the policy-making. There are advantages and drawbacks in each approach, and overlaps between them. • To facilitate comparison, studies of research utilisation are best organised around a conceptual framework. Despite that, the influence of contextual factors in different settings makes it difficult to generalise. • The two methods used most frequently, and usually together, come from the qualitative tradition: documentary analysis and in-depth interviews. Questionnaires, bibliometric analysis, insider knowledge and historical approaches have all been applied. A few recent studies have attempted to score or scale the level of utilisation. • The examples suggest there is a greater level of utilisation and final outcomes in terms of health, health equity, and social and economic gain than is often assumed, whilst still showing much underutilisation. There is considerable variation in the degree of utilisation, both within and between studies. Chapter 4: Key Issues in the Analysis of Research Utilisation in Policy-Making • Increasing attention is focusing on the concept of interfaces between researchers and the users of research. This incorporates the idea that there are likely to be different values and interests between the two communities. • In relation to utilisation, the prioritisation debate revolves around two key aspects: whether priorities are being set that will produce research that policy-makers and others will want to use, and whether priorities are being set that will engage the interests and commitment of the research community. • Interactions across the interface between policy-makers and researchers are important in transferring research to policy-makers. This fits especially well with the interactive model of utilisation. Actions by individual researchers can be useful in generating interaction, but it is desirable to consider the role of the HRS in encouraging or facilitating interactions, networks and mechanisms at a system-wide level. The HRS could provide funding and organisational support for various items including: long-term research centres; research brokerage/translator mechanisms; the creation of official committees of policy-makers and researchers; and mechanisms for review and synthesis of research findings. • There is increased recognition of the significance of policy-makers in their role as the receptors of research. In relation to the perspective of policy-makers there is a spectrum of key questions. These range from whether relevant research is available and effectively being brought to their attention, to whether they are able to absorb it and willing to use it. The HRS has a responsibility, especially in the early parts of the spectrum, but the wider health system also has a responsibility to create appropriate institutional mechanisms and ensure there are staff willing and able to incorporate relevant research. • More attention should be given to the role of incentives, both for researchers to produce utilisable research, and for policy-makers, at the system or individual level, to use it. The assessment of utilisation becomes a key issue if rewards are to focus on relevance as well as research excellence. • An appropriate model for assessing research utilisation in policy-making combines analysis of two issues: the role of receptors and the importance of actions at the interfaces. An emphasis on the role of the receptor is necessary because ultimately it is up to the policy-maker to make the decisions. Any assessment of the success of the HRS in relation to utilisation must accept that the wider political context is beyond the control of the HRS, but consider the activities of the HRS, within its given context, to enhance the utilisation of research by increasing the permeability of the interfaces. Chapter 5: Assessment of Research Utilisation in Health Policy-Making • The reasons for assessing the utilisation of research in policy-making include: advocacy, accountability, and increased understanding. For the World Health Organization there could be a role in conducting such assessments with the aim of providing evidence of the effective use of research resources. This could support advocacy for greater resources to be made available for health research. It is important that the purposes of any assessment are taken into account in planning the methods to be used. • Previous studies demonstrated the difficulties of making generalisations about specific factors associated with high levels of utilisation. To address this in any cross-national WHO initiative involving a series of studies in a range of countries, it would be desirable to structure all the studies around a conceptual framework (such as the interfaces and receptor framework considered here) and base the studies in each country on common themes. These could include policies for the adoption of multi-drug therapy for treating leprosy, and for the equitable access to health services. • Analysis of documents and semi-structured interviews would be appropriate methods in each study assessing the role of research in policy-making on a specific policy theme. Questionnaires could also have a role. These approaches would provide triangulation of methods and data-sources and should also provide material to help identify the relative importance, in relation to the level of utilisation recorded, of the HRS mechanisms described in the previous analysis. The types and sources of research used, and reasons for their use, should also be recorded and attempts made to correlate them with the previous priority setting approaches. It is expected that each study will produce its own narrative or story of what caused utilisation in the particular context, but the data gathered could also be applied to descriptive scales of the level research utilisation. The four scales could cover the consistency of policy with research findings, and the degree of influence of research on agenda setting, policy formulation, and implementation. • The findings from the assessments in each participating country should be collated. For each policy theme or topic the analysis would compare two sets of data: the scales for level of research utilisation in each country, and the contextualised lists of the HRS activities and other mechanisms and networks thought to be important. Although the account here has focused on research impact on policy-making, the evaluations would be stronger as part of a wider analysis covering research utilisation and interactions with practitioners, industry and the public. • Given appropriate and targeted topic and country selection, this approach is likely to meet the purpose of using structured methods to provide examples of effective research utilisation. The approach should contribute towards enhanced understanding of the issues and could provide the basis of an assessment tool which, if used widely in countries, could lead to greater utilisation of health research.Research Policy and Co-operation (RPC) Department of the World Health Organization, Geneva; UK Department of Health’s Policy Research Programme; Alliance for Health Policy and Systems Research from the governments of Norway and Sweden; World Bank and International Development Research Council of Canad

Chemotaxis When Bacteria Remember: Drift versus Diffusion

{\sl Escherichia coli} ({\sl E. coli}) bacteria govern their trajectories by switching between running and tumbling modes as a function of the nutrient concentration they experienced in the past. At short time one observes a drift of the bacterial population, while at long time one observes accumulation in high-nutrient regions. Recent work has viewed chemotaxis as a compromise between drift toward favorable regions and accumulation in favorable regions. A number of earlier studies assume that a bacterium resets its memory at tumbles -- a fact not borne out by experiment -- and make use of approximate coarse-grained descriptions. Here, we revisit the problem of chemotaxis without resorting to any memory resets. We find that when bacteria respond to the environment in a non-adaptive manner, chemotaxis is generally dominated by diffusion, whereas when bacteria respond in an adaptive manner, chemotaxis is dominated by a bias in the motion. In the adaptive case, favorable drift occurs together with favorable accumulation. We derive our results from detailed simulations and a variety of analytical arguments. In particular, we introduce a new coarse-grained description of chemotaxis as biased diffusion, and we discuss the way it departs from older coarse-grained descriptions.Comment: Revised version, journal reference adde

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Biocatalytic Synthesis of Polymers of Precisely Defined Structures

The fabrication of functional nanoscale devices requires the construction of complex architectures at length scales characteristic of atoms and molecules. Currently microlithography and micro-machining of macroscopic objects are the preferred methods for construction of small devices, but these methods are limited to the micron scale. An intriguing approach to nanoscale fabrication involves the association of individual molecular components into the desired architectures by supramolecular assembly. This process requires the precise specification of intermolecular interactions, which in turn requires precise control of molecular structure

Color comparisons and interpersonal variation

An important challenge to color objectivists, who hold that statements concerning color are made true or false by objective (non-subject-involving) facts, is the argument from interpersonal variation in where normal observers locate the unique hues. Recently, an attractive objectivist response to the argument has been proposed that draws on the semantics of gradable adjectives and which does not require defending the idea that there is a single correct location for each of the unique hues (Gómez-Torrente, 2016). In Hansen (2015), I argued that the recent objectivist response doesn’t apply to comparative occurrences of color adjectives, so a revised, comparative, version of the argument from interpersonal variation remains a powerful objection to certain types of objectivism. In this paper, I address several unsatisfactory objectivist replies to the comparative version of the argument from interpersonal variation, and offer what I think is a more plausible objectivist reply to the comparative argument from interpersonal variation

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Optical Trapping with High Forces Reveals Unexpected Behaviors of Prion Fibrils

Amyloid fibrils are important in diverse cellular functions, feature in many human diseases and have potential applications in nanotechnology. Here we describe methods that combine optical trapping and fluorescent imaging to characterize the forces that govern the integrity of amyloid fibrils formed by a yeast prion protein. A crucial advance was to use the self-templating properties of amyloidogenic proteins to tether prion fibrils, enabling their manipulation in the optical trap. At normal pulling forces the fibrils were impervious to disruption. At much higher forces (up to 250 pN), discontinuities occurred in force-extension traces before fibril rupture. Experiments with selective amyloid-disrupting agents and mutations demonstrated that such discontinuities were caused by the unfolding of individual subdomains. Thus, our results reveal unusually strong noncovalent intermolecular contacts that maintain fibril integrity even when individual monomers partially unfold and extend fibril length.National Institutes of Health (U.S.) (Grant GM025874)National Science Foundation (U.S.). CAREER (Award 0643745

The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors

Adaptation of molecular structure to the ligand chemistry and interaction with the cytoskeletal filament are key to understanding the mechanochemistry of molecular motors. Despite the striking structural similarity with kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs). Here, by employing a structure-based model of protein folding, we show that a simple repositioning of the neck-helix makes the dynamics of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our computational model shows that Ncd in solution can have both symmetric and asymmetric conformations with disparate ADP binding affinity, also revealing that there is a strong correlation between distortion of motor head and decrease in ADP binding affinity in the asymmetric state. The nucleotide (NT) free-ADP (?-ADP) state bound to MTs favors the symmetric conformation whose coiled-coil stalk points to the plus-end. Upon ATP binding, an enhanced flexibility near the head-neck junction region, which we have identified as the important structural element for directional motility, leads to reorienting the coiled-coil stalk towards the minus-end by stabilizing the asymmetric conformation. The minus-end directionality of the Ncd motor is a remarkable example that demonstrates how motor proteins in the kinesin superfamily diversify their functions by simply rearranging the structural elements peripheral to the catalytic motor head domain