1-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA).

PURPOSE: To develop a safe and noninvasive in vivo assay of hepatic propionate oxidative capacity. METHODS: A modified 1-13C-propionate breath test was administered to 57 methylmalonic acidemia (MMA) subjects, including 19 transplant recipients, and 16 healthy volunteers. Isotopomer enrichment (13CO2/12CO2) was measured in exhaled breath after an enteral bolus of sodium-1-13C-propionate, and normalized for CO2 production. 1-13C-propionate oxidation was then correlated with clinical, laboratory, and imaging parameters collected via a dedicated natural history protocol. RESULTS: Lower propionate oxidation was observed in patients with the severe mut0 and cblB subtypes of MMA, but was near normal in those with the cblA and mut- forms of the disorder. Liver transplant recipients demonstrated complete restoration of 1-13C-propionate oxidation to control levels. 1-13C-propionate oxidation correlated with cognitive test result, growth indices, bone mineral density, renal function, and serum biomarkers. Test repeatability was robust in controls and in MMA subjects (mean coefficient of variation 6.9% and 12.8%, respectively), despite widely variable serum methylmalonic acid concentrations in the patients. CONCLUSION: Propionate oxidative capacity, as measured with 1-13C-propionate breath testing, predicts disease severity and clinical outcomes, and could be used to assess the therapeutic effects of liver-targeted genomic therapies for MMA and related disorders of propionate metabolism. TRIAL REGISTRATION: This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078.

A day in the life of a Ménière's patient: understanding the lived experiences and mental health impacts of Ménière's disease.

Concepts of social practice are increasingly being used to understand experiences of everyday life, particularly in relation to consumption and healthy lifestyles. This article builds on this in the context of lives disrupted and reshaped by chronic illness. It uses social practice theory to examine the lived experiences of individuals with Ménière's disease; a long-term progressive vestibular disorder, defined by episodes of severe and debilitating vertigo, aural fullness, tinnitus and sensorineural hearing loss. Drawing on the findings of 20 in-depth narrative interviews with Ménière's patients, and eight spousal/partner interviews, we explore the impacts of the condition on sensory, temporal, spatial and social dimensions of the body. In doing so, we highlight the intensely embodied sensory and emotional work required to maintain connections between the 'competences', 'materials' and 'meanings' that constitute and sustain the performance of both mundane and meaningful social practices over time. As connections between these elements of social practice are disrupted during more active phases of the condition, affected individuals may be defected from old practices and recruited to new ones, often requiring both time and social support to find meaning or pleasure in these alternative ways of being in the world.

Lessons from a peer-led obesity prevention programme in English schools.

Obesity in young people is a major public health concern. Energy balance, the interrelationship between diet and physical activity, is known to be a key determinant. Evidence supports the development of school-based approaches to obesity prevention. ASSIST (A Stop Smoking in Schools Trial) is an effective school-based, peer-led smoking prevention programme for 12-13-year-old students, based on diffusion of innovations theory. The AHEAD (Activity and Healthy Eating in ADolescence) study tested the feasibility of adapting ASSIST to an obesity prevention intervention. The AHEAD intervention was tested and refined during a pilot study in one school, followed by an exploratory trial in six schools. Quantitative (self-report behavioural questionnaires and evaluation forms) and qualitative (structured observations, focus groups and interviews) research methods were used to examine the implementation and acceptability of the intervention. The potential effectiveness of the intervention in increasing healthy eating was measured using self-report behavioural questionnaires. Activity monitors (accelerometers) were used to measure physical activity. Results show it was feasible to implement the AHEAD intervention, which was well received. However, implementation was resource and labour intensive and relatively expensive. Furthermore, there was no evidence of promise that the intervention would increase physical activity or healthy eating in adolescents. Although diet and physical activity are both relevant for obesity prevention, the focus on two behaviours appeared too complex for informal diffusion through peer networks. This identifies a tension, particularly for adolescent peer-led health promotion, between the desire not to isolate or oversimplify health behaviours and the need to present clear, succinct health promotion messages.

What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.

BACKGROUND: There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits. METHODS: An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed. DISCUSSION: The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.

A(nother) time for nature? Situating non-human nature experiences within the emotional transitions of sight loss.

Sight impairment is experienced by approximately 253 million people worldwide, including people of all generations, at all life course stages. Caught between past and present embodiments of the world, people often express feelings of loss with the onset of sight impairment. This paper examines the role of nonhuman nature encounters as a contingent resource amongst individuals navigating these emotional transitions. It responds to recent calls to attend to the life course in both critical disability studies and the growing body of work linking nonhuman nature relations to human wellbeing. The paper draws on findings from a qualitative study that combined in-depth narrative interviews with in situ go-along interviews to explore how 31 people with sight impairment in England describe and experience a sense of wellbeing (or otherwise) with nature across their everyday lives and life trajectories. The data were analysed using inductive narrative thematic analysis. While nonhuman nature encounters were valued by many participants in promoting a sense of freedom, relatedness, pleasurable sensory immersion, opportunities for exploration and 'skilling up', this paper cautions against generalised or overly Romantic tropes of what nonhuman nature can 'do' through key sight loss junctures, and for whom. It highlights the value of providing timely and sensitive social scaffolding and nurturing creativity to open up meaningful opportunities to engage with nonhuman nature and to counter feelings of loss exacerbated by identity-limiting life course narratives and disability stereotypes. Informed by the stories shared by participants to chart and situate their experiences of sight loss, we call for a new identity politics within and beyond the growing movement to 'connect' people to nonhuman nature for wellbeing; a politics that affirms diverse forms of more-than-human embodiment, recognising how and why such relations may weave into - and indeed out of - people's varied, interdependent life course trajectories.

Beyond "Move More": Feeling the Rhythms of physical activity in mid and later-life.

The last two decades have seen growing unease regarding the negative health consequences of increasing levels of physical inactivity, both in the UK and further afield. Public health initiatives and interventions aimed at increasing levels of physical activity have, therefore, become somewhat commonplace. Within the current context of demographic change, with growing numbers of older adults and evidence that inactivity increases with age, these initiatives hold particular relevance to mid and later-life adults. Yet despite their prevalence, the policy gains from such promotional efforts have typically been modest at best, demonstrating the limits to decontextualized health messages that encourage people to 'sit less', 'move more' or 'move faster'. In this paper, we draw on the concept of rhythm, to provide an original contribution in response to recent calls to rethink existing approaches to physical activity in mid-life and beyond. We draw from three qualitative data sets from separate studies exploring health, wellbeing and ageing (two in the context of chronic health conditions and sensory impairments). Inspired by facet methodology, we advance knowledge by providing 'flashes of insight' into the subtle patterns and tempos that frame physical activity in mid and later life. In doing so, we offer alternative insight into how people avail themselves to, and experience motion and stillness during these life stages. That alternative, as we also note, has an important role to play in the development of appropriate, relatable health messages regarding movement that recognises 'expertise by experience'.

'Hopeful adaptation' in health geographies: Seeking health and wellbeing in times of adversity.

Living with adversity can create wide-ranging challenges for people's health and wellbeing. This adversity may arise through personal embodied difference (e.g. acquiring a brain injury or losing mobility in older age) as well as wider structural relations that shape a person's capacity to adapt. A number of dichotomies have dominated our understanding of how people engage with health and wellbeing practices in their lives, from classifying behaviours as harmful/health-enabling, to understanding the self as being defined before/after illness. This paper critically interrogates a number of these dichotomies and proposes the concept of 'hopeful adaptation' to understand the myriad, often non-linear ways that people seek and find health and wellbeing in spite of adversity. We highlight the transformative potential in these adaptive practices, rather than solely focusing on how people persist and absorb adversity. The paper outlines an agenda for a health geography of hopeful adaptation, introducing a collection of papers that examine varied forms of adaptation in people's everyday struggles to find health and wellbeing whilst living with and challenging adversity.

Quantification of the Capacity for Cold-Induced Thermogenesis in Young Men With and Without Obesity.

OBJECTIVE: Cold exposure increases energy expenditure (EE) and could have a role in combating obesity. To understand this potential, we determined the capacity for cold-induced thermogenesis (CIT), the EE increase above the basal metabolic rate at the individualized coldest tolerable temperature before overt shivering. DESIGN: During a 13-day inpatient protocol, we quantitated the EE of 12 lean men and 9 men with obesity at various randomly ordered ambient temperatures in a room calorimeter. Subjects underwent brown fat imaging after exposure to their coldest tolerable temperature. RESULTS: CIT capacity was 300 ± 218 kcal/d (mean ± SD) or 17 ± 11% in lean men and 125 ± 146 kcal/d or 6 ± 7% in men with obesity (P = 0.01). The temperature below which EE increased, lower critical temperature (Tlc), was warmer in lean men than men with obesity (22.9 ± 1.2 vs 21.1 ± 1.7°C, P = 0.03), but both had similar skin temperature (Tskin) changes and coldest tolerable temperatures. Whereas lean subjects had higher brown fat activity, skeletal muscle activity increased synchronously with CIT beginning at the Tlc in both groups, indicating that muscle is recruited for CIT in parallel with brown fat, not sequentially after nonshivering thermogenesis is maximal. CONCLUSIONS: Despite greater insulation from fat, men with obesity had a narrower range of tolerable cool temperatures available for increasing EE and less capacity for CIT than lean men, likely as a result of greater basal heat production and similar perception to Tskin cooling. Further study of the reduced CIT capacity in men with obesity may inform treatment opportunities for obesity.

From therapeutic landscapes to healthy spaces, places and practices: A scoping review.

The term 'therapeutic landscapes' was first coined by health geographer, Wilbert Gesler, in 1992 to explore why certain environments seem to contribute to a healing sense of place. Since then, the concept and its applications have evolved and expanded as researchers have examined the dynamic material, affective and socio-cultural roots and routes to experiences of health and wellbeing in specific places. Drawing on a scoping review of studies of these wider therapeutic landscapes published between 2007 and 2016, this paper explores how, where, and to what benefit the 'therapeutic landscapes' concept has been applied to date, and how such applications have contributed to its critical evolution as a relevant and useful concept in health geography. Building on themes included in two earlier (1999, 2007) edited volumes on Therapeutic Landscapes, we summarise the key themes identified in the review, broadly in keeping with the core material, social, spiritual and symbolic dimensions of the concept initially posited by Gesler. Through this process, we identify strengths and limitations of the concept and its applications, as well as knowledge gaps and promising future directions for work in this field, reflecting critically on its value within health geography and its potential contribution to wider interdisciplinary discussions and debates around 'healthy' spaces, places, and related practices.

Ménière's disease and biographical disruption: Where family transitions collide.

People's lived experiences of chronic illness have garnered increasing research interest over the last 30-40 years, with studies recognising the disruptive influence of illness onset and progression, both to people's everyday lives and to their biographical selves. We extend this body of work, drawing on the experiences of people living with Ménière's disease; a long-term progressive vestibular disorder characterised by unpredictable episodes of debilitating vertigo, tinnitus and permanent sensorineural hearing loss. In response to calls for more critical examination of the wider biographical contexts in which chronic illnesses are encountered, we draw on 28 in-depth narrative interviews with Ménière's patients and their family members to discuss how personal chronic illness experiences may be closely entwined with, and deeply shaped by, the life transitions (illness-related and otherwise) of 'linked others'. Interviews were conducted in south west England from January to June 2015. Focusing on intersecting transitions of parenthood, caregiving and retirement, we explore how and why familial relationships can both facilitate and hinder adaptation to a lifetime of chronically disrupted normalities, contributing to fluctuating experiences of 'cherished time', 'anomalous time' and 'turbulent time'. In so doing, we suggest that the onset and progression of chronic illness could usefully be re-conceptualised as one of many 'biographical oscillations' encountered during the life course that serve to re-route us between continually shifting life trajectories. In recognising life's dynamism and challenging the identity-limiting and self-damaging nature of entrenched cultural life course constructions, we suggest value in recognising alternative ways of 'living well' when negotiating the wide-ranging biographical maps that life can follow.

Seeking everyday wellbeing: The coast as a therapeutic landscape.

Recent research suggests coastal environments may promote human health and wellbeing. This article explores the diverse coastal experiences sought out by residents of two towns in south west England to promote and preserve their personal wellbeing in the context of their everyday lives. It draws on the findings of an in-depth interpretive study conducted from May to November 2013 that examined the relative contribution of varied green and blue space experiences to individual wellbeing through the life course. Personalised activity maps produced using accelerometer and Global Positioning System (GPS) data were used to guide in-depth geo-narrative interviews with a purposive sample of 33 participants. This was combined with a subset of nine case study go-along interviews in places deemed therapeutic by the participants themselves, offering deeper insight into the lived experiences and relationships playing out within such places. Situated in a novel adaptation of the therapeutic landscapes framework, this article explores how symbolic, achievement-oriented, immersive and social experiences contributed to participants' sense of wellbeing in their local coastal areas. Participants expressed particularly strong and often enduring connections to the local coastline, with different coastal stretches perceived to cater for varied therapeutic needs and interests, at multiple scales and intensities. The findings suggest the need for greater acknowledgement of people's emotional, deeply embodied and often shared connections to the coast within coastal management policy and practice, both nationally and internationally. Importantly, such efforts should recognise the fluid, dynamic nature of this land-sea boundary, and the valued therapeutic experiences linked to this fluidity.

Green space, health and wellbeing: making space for individual agency.

This essay examines the assumptions of green space use underpinning much existing green space and health research. It considers opportunities to move the field forward through exploring two often overlooked aspects of individual agency: the influence of shifting life circumstances on personal wellbeing priorities and place practices, and the role of personal orientations to nature in shaping how green space wellbeing opportunities are perceived and experienced. It suggests such efforts could provide more nuanced insights into the complex, personal factors that define and drive individual choices regarding the use of green spaces for wellbeing over time, thereby strengthening our understanding of the salutogenic potential (and limits) of green spaces.