Interdisciplinary approaches to a connected landscape: upland survey in the Northern Ochils

The key to understanding a landscape is through its connections, which tie together people and environment within and beyond that landscape and across many different periods. This is particularly true of the northern face of the Ochil Hills in central Scotland, which is characterised by dense networks of connections between lowlands and uplands, local and regional. To trace those connections we integrate the results of walkover survey, aerial archaeology, excavations, documentary analysis and place name analysis, revealing significant continuities and differences in the networks and relationships that have connected this landscape across time and space. Iron Age hillforts used their prominence and monumentality to guide people along very specific routes across the Ochils. Regular seasonal movements of cattle and herders in the medieval and post-medieval periods were closely related to the agriculture and settlement they encountered on the way: this interaction can be clearly seen in the elaborate intertwining of paths, braided cattle tracks, farmsteads and enclosures, most strikingly in the 18th century. Such intricate connections across the landscape are equally keyed in to the specifics of particular locations and to much broader networks and historical change

Amelogenesis imperfecta

Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations

Mediterranean diet adherence and cognitive function in older, UK adults: The EPIC-Norfolk study

Background In Mediterranean countries, adherence to a traditional Mediterranean dietary pattern (MedDiet) is associated with better cognitive function and reduced dementia risk. It is unclear if similar benefits exist in non-Mediterranean regions. Objective To examine associations between MedDiet adherence and cognitive function in an older, UK population. To investigate whether associations differed between individuals with high versus low cardiovascular disease (CVD) risk. Design We conducted an analysis in 8009 older individuals with dietary data at Health Check 1 (1993-1997) and cognitive function data at Health Check 3 (2006-2011) of the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Associations were explored between MedDiet adherence and global and domain specific cognitive test scores and risk of poor cognitive performance in the entire cohort, and when stratified according to CVD risk status. Results Higher MedDiet adherence defined by the Pyramid MedDiet score was associated with better global cognition (β±SE=-0.012±0.002; P<0.001), verbal episodic memory (β±SE=-0.009±0.002; P<0.001), and simple processing speed (β±SE=-0.002±0.001; P=0.013). Lower risk of poor verbal episodic memory (OR(95%CI)=0.784 (0.641,0.959); P=0.018), complex processing speed (OR(95%CI)=0.739 (0.601,0.907); P=0.004), and prospective memory (OR(95%CI)=0.841 (0.724,0.977); P=0.023) was also observed for the highest versus lowest Pyramid MedDiet tertiles. The effect of a one-point increase in Pyramid score on global cognitive function was equivalent to 1.7 fewer years of cognitive ageing. MedDiet adherence defined by the MEDAS score (mapped using both binary and continuous scoring) showed similar, albeit less consistent, associations. In stratified analyses, associations were evident in individuals at higher CVD risk only (P<0.05). Conclusions Higher adherence to the MedDiet is associated with better cognitive function and lower risk of poor cognition in older, UK adults. This evidence underpins the development of interventions to enhance MedDiet adherence, particularly in individuals at higher CVD risk, aiming to reduce the risk of age-related cognitive decline in non-Mediterranean populations

Ecologies of participation in socio-technical change: The case of energy system transitions

Studies of societal engagement with socio-technical change are undergoing a systemic turn. Rather than simply viewing public engagement in science, policy and behavioural change in terms of discrete cases, key social theories in deliberative democracy, practice theory, socio-technical transitions and co-productionist scholarship in science and technology studies (STS) are moving to consider how diverse forms of participation interrelate in wider systems. In this paper we take stock of these advances to develop a conceptual framework for understanding ecologies of participation in socio-technical and democratic systems, grounded in relational co-productionist theory in STS. The framework is illustrated through empirical analysis of a systematic mapping of participation in UK energy system transitions between 2010 and 2015. This provides the first insights into system-wide patternings, diversities and inequalities of energy participation, the significant types of interrelation between practices of public engagement within wider ecologies of participation, and their mutual construction with political cultures and constitutions. The value and implications of adopting an ecologies of participation approach are considered with respect to the theoretical, empirical and practical challenges of understanding and building more inclusive, responsible and just socio-technical (energy) transitions

Expressive free speech, the state, and the public sphere: A Bakhtinian–Deleuzian analysis of ‘public address’ at Hyde Park

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 Taylor & Francis.In this paper I explore how struggles around free speech between social movements and the state are often underpinned by a deeper struggle around expressive images of what counts as either ‘decent’ or ‘indecent’ discussion. These points are developed by exploring what is arguably the most famous populist place for free speech in Britain, namely Hyde Park. In 1872 the state introduced the Parks Regulation Act in order to regulate, amongst other things, populist uses of free speech at Hyde Park. However, although the 1872 Act designated a site in Hyde Park for public meetings, it did not mention ‘free speech’. Rather, the 1872 Act legally enforced the liberty to make a ‘public address’ and this was implicitly contrasted by the state of an expressive image of ‘indecent’ speakers exercising their ‘right’ of free speech at Hyde Park. Once constructed, the humiliating image of ‘indecent’ free speech could then be used by the state to regulate actual utterances of public speakers at Hyde Park. But the paper shows how in the years immediately following 1872 a battle was fought out in Hyde Park over the expressive image of public address between the state and regulars using Hyde Park as a public sphere to exercise free speech. For its part the state had to engage in meaningful deliberative forms of discussion within its own regulatory framework and with the public sphere at Hyde Park in order to maintain the legal form, content and expression of the 1872 Act. To draw out the implications of these points I employ some of the theoretical ideas of the Bakhtin Circle and Gilles Deleuze. Each set of thinkers in their own way make valuable contributions for understanding the relationship between the state, public sphere and expressive images

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: Protocol for the MedEx-UK randomised controlled trial

Introduction Dementia prevalence continues to increase, and effective interventions are needed to prevent, delay or slow its progression. Higher adherence to the Mediterranean diet (MedDiet) and increased physical activity (PA) have been proposed as strategies to facilitate healthy brain ageing and reduce dementia risk. However, to date, there have been no dementia prevention trials in the UK focussed on combined dietary and PA interventions. This study aims to: (1) assess feasibility and acceptability of a theory-underpinned digital and group-based intervention for dementia risk reduction in an 'at risk' UK cohort; (2) evaluate behaviour change responses to the intervention; and, (3) provide information on cognitive, neurological, vascular and physiological outcomes to inform the design of a follow-on, full-scale efficacy trial. Methods One hundred and eight participants aged 55 to 74 years with a QRISK2 score of ≥10% will be recruited to take part in this 24-week multi-site study. Participants will be randomised into three parallel arms: (1) Control; (2) MedDiet; and, (3) MedDiet+PA. The study will evaluate a personalised website, group session and food delivery intervention to increase MedDiet adherence and PA in older adults at risk of dementia. Diet and PA will be monitored prior to, during and following the intervention. Feasibility, acceptability and hypothesised mediators will be assessed in addition to measures of cognitive function, brain structure/perfusion (MRI), vascular function and metabolic markers (blood, urine and faecal) prior to, and following, the intervention. Discussion This trial will provide insights into the feasibility, acceptability and mechanism of effect of a multi-domain intervention focussed on the MedDiet alone and PA for dementia risk reduction in an 'at risk' UK cohort. Ethics and dissemination The study has received NHS REC and HRA approval (18/NI/0191). Findings will be disseminated via conference presentations, public lectures, and peer-reviewed publications. Trial registration details ClinicalTrials.gov NCT03673722

A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

Determination of Beta-Defensin Genomic Copy Number in Different Populations: A Comparison of Three Methods

There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and β-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with disease. At present, real-time quantitative PCR (QPCR) is the most commonly used method to determine gene copy number, however the Paralogue Ratio Test (PRT) is being used in more and more laboratories.In this study we compare a Pyrosequencing-based Paralogue Ratio Test (PPRT) for determining beta-defensin gene copy number with two currently used methods for gene copy number determination, QPCR and triplex PRT by typing five different cohorts (UK, Danish, Portuguese, Ghanaian and Czech) of DNA from a total of 576 healthy individuals. We found a systematic measurement bias between DNA cohorts revealed by QPCR, but not by the PRT-based methods. Using PRT, copy number ranged from 2 to 9 copies, with a modal copy number of 4 in all populations.QPCR is very sensitive to quality of the template DNA, generating systematic biases that could produce false-positive or negative disease associations. Both triplex PRT and PPRT do not show this systematic bias, and type copy number within the correct range, although triplex PRT appears to be a more precise and accurate method to type beta-defensin copy number

Chronic Allergic Inflammation Causes Vascular Remodeling and Pulmonary Hypertension in Bmpr2 Hypomorph and Wild-Type Mice

Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene have been identified in patients with heritable pulmonary arterial hypertension (PAH); however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT) Balb/c/Byj mice were exposed to house dust mite (HDM) allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP) was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR) to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations