Vascular calcification and mineral bone disorder in chronic kidney disease

Chronic Kidney Disease (CKD), osteoporosis and mild hyponatremia are all prevalent chronic conditions that may coexist and are often under-recognized. Mineral-Bone Disorder begins early in the natural history of CKD and results in complex abnormalities of bone which ultimately confers a well-established increased risk of fragility fractures in End Stage Kidney Disease. Hyponatremia is a novel, usually renal mediated metabolic perturbation, that most commonly occurs independently of the stage of renal dysfunction but which may also predispose to increased fracture risk. The extent -if any- to which either early stages of renal dysfunction or the presence of hyponatremia contribute to fracture occurrence in the general population, independently of osteoporosis, is unclear. Renal transplantation is the treatment of choice for ESKD and although it restores endogenous renal function it typically fails to normalize either the long term cardiovascular or fracture risk. One potential mechanism contributing to these elevated long-term risks and to diminished Health Related Quality of Life is persistent, post-transplant hyperparathyroidism. In this study we retrospectively examine the association of renal function and serum sodium with Bone Mineral Density and fracture occurrence in a retrospective cohort of 1930 female members of the general population who underwent routine DXA scan. We then prospectively recruited a cohort of 90 renal transplant recipients in order to examine the association of post transplant parathyroid hormone (PTH) level with measures of CKD Mineral Bone Disorder, including, DXA Bone Mineral Density, Vascular Calcification (assessed using both abdominal radiography and CT techniques, as well as indirectly by carotid-femoral Pulse Wave Velocity) and Quality of Life (using the Short Form-12 and a PTH specific symptom score). In the retrospective DXA cohort, moderate CKD (eGFR 30-59ml/min/1.73m2) and hyponatremia (<135mmol/L) were associated with fracture occurrence, independently of BMD, with an adjusted Odds Ratio (95% Confidence Interval), of 1.37 (1.0, 1.89) and 2.25 (1.24, 4.09) respectively. In the renal transplant study, PTH was independently associated with the presence of osteoporosis, adjusted Odds Ratio (95% Confidence Interval), 1.15 (per 10ng/ml increment), (1.04, 1.26). The presence of osteoporosis but not PTH was independently associated with measures of vascular calcification, adjusted ß (95% Confidence Interval), 12.45, (1.16, 23.75). Of the eight quality-of-life domains examined, post-transplant PTH (per 10ng/ml increment), was only significantly and independently associated with reduced Physical Functioning, (95% Confidence Interval), 1.12 (1.01, 1.23). CKD and hyponatremia are both common health problems that may contribute to fracture occurrence in the general population, a major on-going public health concern. PTH and decreased Bone Mineral Density may signal sub-optimal long-term outcomes post renal transplantation, influencing bone and vascular health and to a limited extent long term Health Related Quality of Life

Thomas Wolfe and the genre question: Beyond the "charge of autobiography"

The North Carolinian author Thomas Wolfe (1900‐1938) has long suffered under the “charge of autobiography,” which lingers to this day in critical assessments of his work. Criticism of Wolfe is frequently concerned with questions of generic classification, but since the 1950s, re‐assessments of Wolfe’s work have suggested that Wolfe’s “autobiographical fiction” exhibits a complexity that merits further investigation. Strides in autobiographical and narrative theory have prompted reconsiderations of texts that defy the artificial boundaries of autobiography and fiction. Wolfe has been somewhat neglected in the canon of American fiction of his era, but deserves to be reconsidered in terms of how he engages with the challenges and contradictions of writing about or around the self. This thesis investigates why Wolfe’s work has been the source of considerable critical discomfort and confusion with regard to the relationship between Wolfe’s life and his writing. It explores this issue through an examination of elements of Wolfe’s work that problematise categorisation. Firstly, it investigates the concept of Wolfe as “storyteller.” It explores the motivations and philosophies that underpin Wolfe’s work and his concept of himself as a teller of tales, and examines aspects of Wolfe’s writing process that have their roots in medieval traditions of the memorisation and recitation of tales. The thesis then conducts a detailed examination of how Wolfe describes the process of transforming his memory into narrative through writing. The latter half of the thesis examines narrative techniques used by Wolfe, firstly analysing his extensive use of the iterative and pseudo‐iterative modes, and then his unusual deployment of narrators and focalization. This project sheds light on elements of Wolfe’s approach to writing and narrative strategies that he employs that have previously been overlooked, and that have created considerable critical confusion with regard to the supposedly “autobiographical” genesis of his work.