Development of an improved internal dose assessment methodology for plutonium

Plutonium is carcinogenic when it is taken into the body because it is an alpha particle emitter. There is limited direct epidemiological evidence of the scale of specific risks from plutonium intake. Assessing doses arising from plutonium exposure is an onerous task. Doses have to be assessed from urine samples and mathematical models which describe the passage of plutonium through the body. Information on plutonium absorption, distribution, metabolism and excretion is very limited. Models of plutonium transport within the body continue to evolve. Different assessment methodologies have been employed to assess plutonium doses for worker cohorts. A review of existing methodologies for producing plutonium doses has been conducted. A strategy for setting research priorities based on their potential impact on estimates of risk is discussed. Ways of improving plutonium dose reconstruction, including the production of reliability/uncertainty estimates are investigated. Efforts to harmonize approaches to the production of doses for the major plutonium worker cohorts are discussed. Recommendations are made for methodological approaches to plutonium dosimetry to meet current epidemiological research needs. The way in which the recommended methodological approach has been implemented for one major plutonium worker cohort is described. Some potential future research priorities are suggested

Disability, skills and employment: a review of recent statistics and literature on policy and initiatives (Research report 59)

"The Centre for Research in Education, Inclusion and Diversity at the University of Edinburgh was... commissioned to review the current literature, statistics and debates, in order to inform the Commission’s work aimed at narrowing the employment and skills gap between disabled and non-disabled people." - Page 1

Characterisation of the hydrological processes and responses to rehabilitation of a headwater wetland of the Sand River, South Africa.

Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.The erosion of headwater wetlands in the Sand River catchment, in the lowveld of north-eastern South Africa has led to a focus on their rehabilitation, both for livelihood security for those that use them for subsistence agriculture, as well as for provision of streamflow regulation services for the Sand River itself. One such wetland, the Craigieburn-Manalana itself undergoing severe erosion was subject to technical rehabilitation using concrete weirs and gabion dams to stabilize the erosion gullies during 2007. Through a series of papers the research discussed in this thesis examined the response of the wetland?s hydrodynamics to the implementation of these measures. Through the installation of a network of hydrometric apparatus the research has shown that the wetlands hydrology is largely controlled by the presence of both horizontal and vertical clay aquicludes within a hydraulically conductive sandy matrix. The sequence of these aquicludes had allowed for artesian phreatic surface phenomena identified in a relatively hydrologically intact region of the wetland. The gully erosion had initiated hydraulic drawdown of the wetland?s water table leading to the desiccation of the system. The construction of a buttress weir within the erosion gully had restored the wetlands hydrodynamics to that typical of conditions upstream of a clay-plug. The research also explored the role that clay plays in terms of controlling the wetland?s hydro-geomorphic setting through geophysical analysis. A conceptual model was then derived that states that these wetlands are held in place by clay-plugs that form through clay illuviation from the hillslopes at regions of valley confinement. This has important implications for the connectivity of wetland process domains. The research also determined the inputs of surface and subsurface flows to the wetland and it was found through detailed examination of soil moisture responses and variably saturated soil physics modelling using the HYDRUS model, that the wetland is hydrologically connected to its contributing hillslope by threshold induced preferential flow pathways, via macropores, that only respond after specific antecedent soil moisture conditions are met. In addition, the thesis describes novel approaches to use information provided by soil scientists for the development of catchment hydrological models. It was shown that the use of this hydropedology information improved the low flow response function of the catchment model, ACRU. This development has important implications for up-scaling of catchment process domains, or hydrological response units by being able to generalize on hillslope hydrological responses based on configuration of their soil type elements. The research also undertook to examine the role that the wetlands play in catchment processes. It was found through water budgeting, supported by hydrological time-series, stable isotope analysis and the quantification of vegetation water use within the wetland and contributing catchment, that these wetlands do not augment baseflows during the dry season. Furthermore, it is only early on during the wet season that these systems may attenuate peak flows, thereafter they act as conduits for high storm flows. Similarities emanated from this research with previous hydrological studies of headwater wetland systems in southern Africa and these are discussed

Kruger National Park research supersites: Establishing long-term research sites for cross-disciplinary, multiscaled learning

Researchers interested in studying the effects of fire or herbivory in the Kruger National Park (KNP) often focus their research activities on the experimental burn plots or herbivore exclosure camps, respectively. These are manipulated sites that apply treatments, for example annual fires or total exclusion of fire and herbivores. However, many projects aim to study or monitor patterns and processes emerging under non-manipulated conditions, typically at sites with contrasting geologies and rainfall. Yet, these sites are usually selected in a haphazard and uncoordinated manner for different projects and, as a consequence, it is often not possible to integrate datasets and knowledge. An alternative to the ever-increasing number of unrelated sites scattered across the park are the ‘KNP research supersites’ which have been earmarked to geographically focus future research effort, acting as data-rich, long-term sites for monitoring and research. In this paper, we introduced the four recently established KNP research supersites, which cover the rainfall gradient and geological contrast of the KNP, presenting their rationale, selection criteria and location, along with existing datasets that describe their herbaceous biomass, woody cover, phenology, fire history, levels of herbivory. Additional site-specific datasets, which are already available, or which are in preparation, were outlined together with details for assessing these open-source datasets online. Conservation implications: The KNP research supersites will become increasingly used for research, monitoring and remote-sensing calibration and ground-truthing purposes. Scientists are encouraged to gain from, and contribute towards, these sites, which will facilitate long-term data collection, data-sharing and co-learning and, ultimately, lead to a more integrated, multiscaled and multitemporal understanding of savannahs

Toward adaptive water governance: the role of systemic feedbacks for learning and adaptation in the eastern transboundary rivers of South Africa

This paper contributes to scholarship on adaptive water governance (AWG), following policy reforms in South Africa, through a focus on systemic feedbacks for learning and adaptation as critical aspects of AWG. We draw insights from three innovative and evolving water governance experiments. In 1998 South Africa adopted integrated water resources management (IWRM) as a transformative approach for achieving an equitable, sustainable, and decentralized stakeholder-centered water resources governance: all hallmarks of an enabling environment for a two-decade history of AWG, although not named as such. Progress in AWG is explored by using a longitudinal, evaluative exploration of three cases in two transboundary basins in South Africa, with a focus on the unfolding enabling environment for achieving sustainability and equity. Building on previous work, we present and discuss a range of enablers that are shown to function systemically to support feedbacks and build adaptive capacity and resilience in complex and uncertain river systems. In the Crocodile Basin, meta-governance arrangements that created an enabling space for collaborative experimentation and learning proved critical as feedbacks were progressively strengthened and embedded through evolving social and institutional arrangements. The enabling environment also supported a networked, blended system of stakeholder- and state-led platforms that have co-evolved through experimentation and learning. Despite progress, long-term persistence of action-learning feedbacks appears less certain in the Olifants Basin cases. We suggest that enabling meta-governance arrangements that offer an institutional home within which to embed learning is critical. The need to explore alternative networked governance arrangements and to explicitly manage for feedbacks that enhance learning at multiple scales is emphasized. We conclude with recommendations for future work on AWG, including reconciling differences between AWG and IWRM that originally framed South African reforms

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. Design: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation