The Uniform World Model: A Methodology for Predicting the Health Impacts of Air Pollution

47 p.

Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS

Background: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. Results: To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomatic age (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1(G93A) mice, the most widely used animal model of ALS. We first identified unique hSOD1(G93A) microglia transcriptomic profile that, in addition to more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of the tumour suppressor gene breast cancer susceptibility gene 1 (Brca1). Secondly, comparison with our previous data on hSOD1(G93A) motoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we established that Brca1 protein is specifically expressed in human spinal microglia and is up-regulated in ALS patients. Conclusions: Overall, our data provide new insights into the pathogenic concept of a non-cell-autonomous disease and the involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possible contributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data points toward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases.

Policy entrepreneurship in the development of public sector strategy: the case of London health reform

The development of health policy is recognized as complex; however, there has been little development of the role of agency in this process. Kingdon developed the concept of policy entrepreneur (PE) within his ‘windows’ model. He argued inter-related ‘policy streams' must coincide for important issues to become addressed. The conjoining of these streams may be aided by a policy entrepreneur. We contribute by clarifying the role of the policy entrepreneur and highlighting the translational processes of key actors in creating and aligning policy windows. We analyse the work in London of Professor Sir Ara Darzi as a policy entrepreneur. An important aspect of Darzi's approach was to align a number of important institutional networks to conjoin related problems. Our findings highlight how a policy entrepreneur not only opens policy windows but also yokes together a network to make policy agendas happen. Our contribution reveals the role of clinical leadership in health reform.

Broadening public input into science policy decision making: can the democratic model for science communication influence scientific, innovation and technological trajectories?

This PhD thesis investigates the potential use of science communication models to engage a broader swathe of actors in decision making in relation to scientific and technological innovation in order to address possible democratic deficits in science and technology policy-making. A four-pronged research approach has been employed to examine different representations of the public(s) and different modes of engagement. The first case study investigates whether patient-groups could represent an alternative needs-driven approach to biomedical and health sciences R & D. This is followed by enquiry into the potential for Science Shops to represent a bottom-up approach to promote research and development of local relevance. The barriers and opportunities for the involvement of scientific researchers in science communication are next investigated via a national survey which is comparable to a similar survey conducted in the UK. The final case study investigates to what extent opposition or support regarding nanotechnology (as an emerging technology) is reflected amongst the YouTube user community and the findings are considered in the context of how support or opposition to new or emerging technologies can be addressed using conflict resolution based approaches to manage potential conflict trajectories. The research indicates that the majority of communication exercises of relevance to science policy and planning take the form of a one-way flow of information with little or no facility for public feedback. This thesis proposes that a more bottom-up approach to research and technology would help broaden acceptability and accountability for decisions made relating to new or existing technological trajectories. This approach could be better integrated with and complementary to government, institutional, e.g. university, and research funding agencies activities and help ensure that public needs and issues are better addressed directly by the research community. Such approaches could also facilitate empowerment of societal stakeholders regarding scientific literacy and agenda-setting. One-way information relays could be adapted to facilitate feedback from representative groups e.g. Non-governmental organisations or Civil Society Organisations (such as patient groups) in order to enhance the functioning and socio-economic relevance of knowledge-based societies to the betterment of human livelihoods.

The vertebrate taxonomy ontology: a framework for reasoning across model organism and species phenotypes.

BACKGROUND: A hierarchical taxonomy of organisms is a prerequisite for semantic integration of biodiversity data. Ideally, there would be a single, expansive, authoritative taxonomy that includes extinct and extant taxa, information on synonyms and common names, and monophyletic supraspecific taxa that reflect our current understanding of phylogenetic relationships. DESCRIPTION: As a step towards development of such a resource, and to enable large-scale integration of phenotypic data across vertebrates, we created the Vertebrate Taxonomy Ontology (VTO), a semantically defined taxonomic resource derived from the integration of existing taxonomic compilations, and freely distributed under a Creative Commons Zero (CC0) public domain waiver. The VTO includes both extant and extinct vertebrates and currently contains 106,947 taxonomic terms, 22 taxonomic ranks, 104,736 synonyms, and 162,400 cross-references to other taxonomic resources. Key challenges in constructing the VTO included (1) extracting and merging names, synonyms, and identifiers from heterogeneous sources; (2) structuring hierarchies of terms based on evolutionary relationships and the principle of monophyly; and (3) automating this process as much as possible to accommodate updates in source taxonomies. CONCLUSIONS: The VTO is the primary source of taxonomic information used by the Phenoscape Knowledgebase (http://phenoscape.org/), which integrates genetic and evolutionary phenotype data across both model and non-model vertebrates. The VTO is useful for inferring phenotypic changes on the vertebrate tree of life, which enables queries for candidate genes for various episodes in vertebrate evolution.

A conceptual model and key variables for guiding supportive interventions for family caregivers of people receiving palliative care

According to the World Health Organization, the patient and family should be viewed as the "unit of care" when palliative care is required. Therefore family caregivers should receive optimal supportive care from health professionals. However, the impact of supporting a dying relative is frequently described as having negative physical and psychosocial sequalae. Furthermore, family caregivers consistently report unmet needs and there has been a dearth of rigorous supportive interventions published. In addition, comprehensive conceptual frameworks to navigate the family caregiver experience and guide intervention development are lacking. This article draws on Lazarus and Folkman's seminal work on the transactional stress and coping framework to present a conceptual model specific to family caregivers of patients receiving palliative care. A comprehensive account of key variables to aid understanding of the family caregiver experience and intervention design is provided.

Physical activity and the rejuvenation of Connswater (PARC study): protocol for a natural experiment investigating the impact of urban regeneration on public health

Background: There is a dearth of evidence regarding the impact of urban regeneration projects on public health, particularly the nature and degree to which urban regeneration impacts upon health-related behaviour change. Natural experiment methodology enables comprehensive large-scale evaluations of such interventions. The Connswater Community Greenway in Belfast is a major urban regeneration project involving the development of a 9 km linear park, including the provision of new cycle paths and walkways. In addition to the environmental improvements, this complex intervention involves a number of programmes to promote physical activity in the regenerated area. The project affords a unique opportunity to investigate the public health impact of urban regeneration.

Methods/Design: The evaluation framework was informed by the socio-ecological model and guided by the RE-AIM Framework. Key components include: (1) a quasi-experimental before-and-after survey of the Greenway population (repeated cross-sectional design), in tandem with data from a parallel Northern Ireland-wide survey for comparison; (2) an assessment of changes in the local built environment and of walkability using geographic information systems; (3) semi-structured interviews with a purposive sample of survey respondents, and a range of community stakeholders, before and after the regeneration project; and (4) a cost-effectiveness analysis. The primary outcome is change in proportion of individuals identified as being regularly physically active, according to the current UK recommendations. The RE-AIM Framework will be used to make an overall assessment of the impact of the Greenway on the physical activity behaviour of local residents.

Discussion: The Connswater Community Greenway provides a significant opportunity to achieve long-term, population level behaviour change. We argue that urban regeneration may be conceptualised meaningfully as a complex intervention comprising multiple components with the potential, individually and interactively, to affect the behaviour of a diverse population. The development and implementation of our comprehensive evaluation framework reflects this complexity and illuminates an approach to the empirical, rigorous evaluation of urban regeneration. More specifically, this study will add to the much needed evidence-base about the impact of urban regeneration on public health as well as having important implications for the development of natural experiment methodology.

Assessing parenting capacity in child protection: towards a knowledge-based model

The assessment of parenting capacity continues to engender public concern in cases of suspected harm to children. This paper outlines a model for approaching this task based on the application of three key domains of knowledge in social work relating to facts, theory and practice wisdom. The McMaster Model of Family Assessment is identified out of this process and reworked to give it a sharper focus on parenting roles and responsibilities. Seven formative dimensions of parenting are then elicited and combined with an analytical process of identifying strengths, concerns, prospects for growth and impact on child outcomes. The resulting assessment framework, it is argued, adds rigour to professional judgements about parenting capacity and enhances formulations on risk in child protection.