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This article offers a close reading of Zoë Wicomb’s novel Playing in the Light (2006), arguing that the novel’s representation of racial passing, linguistic performance, and value present a radical departure from standard accounts of racial passing. In Wicomb’s novel, individual advancement and social mobility are central aspirations both to the “play-whites” in the novel as well as to the postapartheid author-figure. In this way Wicomb’s novel highlights not only the economic underpinnings of racial identity, but the continuation of racial exclusion in postapartheid South Africa. The novel provides an especially perceptive representation of racial capitalism in which the linguistic dominance of English, the development of neoliberalism, and continued hyper-exploitation produce a context in which social mobility is still dependent on passing.

Racialised inequality has existed in South Africa since the arrival of the first settlers, so that the shadow of illegitimacy has fallen upon successive governments and ruling classes. Along with changing political and material contexts, claims to legitimacy have been altered and reformulated. This thesis argues that these discourses have been instrumental to the development of the novel in South Africa, and that representations of totality and history have necessarily sought to support, critique or reformulate these discourses. Two decades after apartheid, South Africa remains a profoundly unequal society. Therefore the scope of this thesis spans the years from the 1940s to the 2000s, using historical-contextual and close reading to determine how specific novels have registered and responded to drives to counter, justify or legitimate the power of a small ruling class. Discourses of legitimacy have travelled under various guises - from sexuality and white supremacy, to paternalist hierarchies, internecine cultural rivalries, claims of popular consent, pragmatism and depoliticisation and the collapse of class into racial difference. By focusing on these I attempt to historicise formal questions about the South African novel, like the prominence of didacticism and difficulties of representing spontaneity. I argue that an individualized and identity-based moralism about racism has been shaped by class interests - and that this has led to an equivalent blindness to the historically specific character of race and racism in South African prose narrative. In this vein, each chapter offers a close reading which challenges orthodox readings by highlighting the salience of class and legitimacy. Readings are offered of the work of Sarah Gertrude Millin, in terms of cultural rivalries between English-speakers and Afrikaners at the dawn of apartheid; of Nadine Gordimer's Late Bourgeois World, in terms of 1960s' repression and dissent; and of John Miles's Kroniek uit die doofpot, in terms of late apartheid's purportedly \"non-ideological\" emphasis on pragmatism and technocracy. The thesis also departs from the ruling party's discourse to consider the way in which legitimacy was constructed by antiapartheid Nationalist movements. Thus, novelistic depictions of the 1976 Soweto Uprising by Miriam Tlali, Mbulelo Mzamane, Sipho Sepamla and Mongane Serote, prefigure the class divisions and tensions in contemporary South Africa. It concludes with a consideration of Achmat Dangor's Bitter Fruit and Zoë Wicomb's Playing in the Light, fictions in which postapartheid discourses and the construction of a heroic nationalist narrative are read against continuing inequality, class immobility and the troubled legitimacy of the national elite.

Background The CapaCiTY programme includes three, multi-centre, randomised controlled trials aiming to develop an evidence based adult chronic constipation treatment pathway. The trials were conducted in the United Kingdom, National Health Service, aiming to recruit 808 participants from 26 March 2015 to 31 January 2019. Sites were selected based on their responses to site feasibility questionnaires (2014–2015), a common tool employed by sponsors to assess a site’s recruitment potential and ability to undertake the trial protocol. Failure to recruit the planned sample jeopardises reliability of results and wastes significant time and resources. The purpose of this study was to investigate barriers to recruitment in 2017. Methods We conducted site feasibility assessments with thirty-nine sites prior to trial commencement. Twenty-seven were selected to participate in the CapaCiTY programme, twelve were deemed unsuitable. We compared site contracted recruitment rates with actual recruitment rates and conducted a telephone survey and analysis from 5 July to 7 December 2017 ( n  = 24) to understand barriers to recruitment. Three sites declined to participate in the survey. Results At the time of survey, 15% of sites in the CapaCiTY programme were meeting recruitment targets, 85% were recruiting half or less of their target. Of these, 28% recruited no participants. The main barriers to recruitment were lack of resources, high workloads, lack of suitable participants and study design not being compatible with routine care. Despite multiple strategies employed to overcome these barriers, the trials were eventually stopped due to futility, recruiting only 34% of the programme sample size. Conclusions Improving the reliability of site feasibility assessments could potentially save a substantial amount in failed research investments and speed up the time to delivery of new treatments. We recommend 1) investment in training researchers in conducting and completing site feasibility; 2) funders to require pilot and feasibility data in grant applications, with an emphasis on patient and public involvement in trial design; 3) conducting site feasibility assessment at the pre-award stage; 4) development of a national database of sites’ previous trial recruitment performance; 5) data-driven site level assessment of recruitment potential. Trial registration ISRCTN11791740; 16/07/2015, ISRCTN11093872; 11/11/2015, ISRCTN11747152; 30/09/2015.

The nuclear receptor Rev-erbα, a powerful repressor of transcription, is shown to link circadian and thermogenic networks by regulating the function of brown adipose tissue. Body temperature control in changing conditions In addition to daily circadian oscillation of body temperature, mammals are able to protect their core body temperature from the cold. This study identifies the nuclear receptor Rev-erb , a repressor of transcription, as a link between circadian and thermogenic networks and body temperature rhythmicity through the regulation of brown adipose tissue function. Mice exposed to cold fare dramatically better in the morning when Rev-erbα is barely expressed than at five in the afternoon when Rev-erbα is abundant, and deletion of the Rev-erbα gene improves cold tolerance. Rev-erbα is shown to function as a physiological repressor of uncoupling protein 1 (Ucp1) in brown adipose tissue, thereby acting to maintain body temperature rhythm in an environmentally responsive manner. Circadian oscillation of body temperature is a basic, evolutionarily conserved feature of mammalian biology 1 . In addition, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure 2 . However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Here we show that the nuclear receptor Rev-erbα (also known as Nr1d1), a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown adipose tissue (BAT) function. Mice exposed to cold fare considerably better at 05:00 (Zeitgeber time 22) when Rev-erbα is barely expressed than at 17:00 (Zeitgeber time 10) when Rev-erbα is abundant. Deletion of Rev-erbα markedly improves cold tolerance at 17:00, indicating that overcoming Rev-erbα-dependent repression is a fundamental feature of the thermogenic response to cold. Physiological induction of uncoupling protein 1 (Ucp1) by cold temperatures is preceded by rapid downregulation of Rev-erbα in BAT. Rev-erbα represses Ucp1 in a brown-adipose-cell-autonomous manner and BAT Ucp1 levels are high in Rev-erbα -null mice, even at thermoneutrality. Genetic loss of Rev-erbα also abolishes normal rhythms of body temperature and BAT activity. Thus, Rev-erbα acts as a thermogenic focal point required for establishing and maintaining body temperature rhythm in a manner that is adaptable to environmental demands.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Human activity in the last century has led to a significant increase in nitrogen (N) emissions and atmospheric deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the deposition of pollution that would be harmful to ecosystems is the determination of critical loads. A critical load is defined as the input of a pollutant below which no detrimental ecological effects occur over the long-term according to present knowledge. The objectives of this project were to synthesize current research relating atmospheric N deposition to effects on terrestrial and freshwater ecosystems in the United States, and to estimate associated empirical N critical loads. The receptors considered included freshwater diatoms, mycorrhizal fungi, lichens, bryophytes, herbaceous plants, shrubs, and trees. Ecosystem impacts included: (1) biogeochemical responses and (2) individual species, population, and community responses. Biogeochemical responses included increased N mineralization and nitrification (and N availability for plant and microbial uptake), increased gaseous N losses (ammonia volatilization, nitric and nitrous oxide from nitrification and denitrification), and increased N leaching. Individual species, population, and community responses included increased tissue N, physiological and nutrient imbalances, increased growth, altered root  :  shoot ratios, increased susceptibility to secondary stresses, altered fire regime, shifts in competitive interactions and community composition, changes in species richness and other measures of biodiversity, and increases in invasive species. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1-39 kg N·ha −1 ·yr −1 , spanning the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, and trees. The critical load approach is an ecosystem assessment tool with great potential to simplify complex scientific information and communicate effectively with the policy community and the public. This synthesis represents the first comprehensive assessment of empirical critical loads of N for major ecoregions across the United States.

Misfolding of normal prion protein (PrP C ) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes. Cognition and mood are linked to the neurophysiology of the limbic system. Little is known about how the disease affects the synaptic activity in brain parts associated with this system. We hypothesize that the dysfunction of synaptic transmission in the limbic regions correlates with the onset of reduced cognition and behavioral deficits. Here, we studied how prion infection in mice disrupts the synaptic function in three limbic regions, the hippocampus, hypothalamus, and amygdala, at a pre-clinical stage (mid-incubation period) and early clinical onset. PrD caused calcium flux dysregulation associated with lesser spontaneous synchronous neuronal firing and slowing neural oscillation at the pre-clinical stage in the hippocampal CA1, ventral medial hypothalamus, and basolateral amygdala (BLA). At clinical onset, synaptic transmission and synaptic plasticity became significantly disrupted. This correlated with a substantial depletion of the soluble prion protein, loss of total synapses, abnormal neurotransmitter levels and synaptic release, decline in synaptic vesicle recycling, and cytoskeletal damage. Further, the amygdala exhibited distinct disease-related changes in synaptic morphology and physiology compared with the other regions, but generally to a lesser degree, demonstrating how different rates of damage in the limbic system influence the evolution of clinical disease. Overall, PrD causes synaptic damage in three essential limbic regions starting at a preclinical stage and resulting in synaptic plasticity dysfunction correlated with early disease signs. Therapeutic drugs that alleviate these early neuronal dysfunctions may significantly delay clinical onset.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at −40 °C prior to distribution and the participants are instructed to store the samples frozen at −20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC–MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.