IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154-CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice.

In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells. IL-2-mediated Treg expansion in combination with short-term CD154-CD40 co-stimulation blockade, but not CTLA-4 Ig or rapamycin, led to tolerance to MHC-mismatched skin grafts in non-lymphopenic mice, mainly by hindering alloreactive CD8(+) effector T cells and the production of alloantibodies. Importantly, this treatment also allowed prolonged survival of allografts in the presence of either donor-specific or cross-reactive memory cells. However, late rejection occurred in sensitized hosts, partly mediated by activated B cells. Overall, these data illustrate the potential but also some important limitations of Treg-based therapy in clinical SOT as well as the importance of concomitant immunomodulatory strategies in particular in sensitized hosts

Mainstreaming Underutilized Indigenous and Traditional Crops into Food Systems: A South African Perspective

Business as usual or transformative change? While the global agro-industrial food system is credited with increasing food production, availability and accessibility, it is also credited with giving birth to ‘new’ challenges such as malnutrition, biodiversity loss, and environmental degradation. We reviewed the potential of underutilized indigenous and traditional crops to bring about a transformative change to South Africa’s food system. South Africa has a dichotomous food system, characterized by a distinct, dominant agro-industrial, and, alternative, informal food system. This dichotomous food system has inadvertently undermined the development of smallholder producers. While the dominant agro-industrial food system has led to improvements in food supply, it has also resulted in significant trade-offs with agro-biodiversity, dietary diversity, environmental sustainability, and socio-economic stability, especially amongst the rural poor. This challenges South Africa’s ability to deliver on sustainable and healthy food systems under environmental change. The review proposes a transdisciplinary approach to mainstreaming underutilized indigenous and traditional crops into the food system, which offers real opportunities for developing a sustainable and healthy food system, while, at the same time, achieving societal goals such as employment creation, wellbeing, and environmental sustainability. This process can be initiated by researchers translating existing evidence for informing policy-makers. Similarly, policy-makers need to acknowledge the divergence in the existing policies, and bring about policy convergence in pursuit of a food system which includes smallholder famers, and where underutilized indigenous and traditional crops are mainstreamed into the South African food system

Suspicious Minds: Apportioning and Avoiding Blame for Distrustful Relationships and Deferring Medical Treatment in South Africa

This paper examines elements of mistrust, blame and suspicion among patients and providers in the South African health system which affect practice and policy development. Using stories told by patients and providers in Cape Town, Johannesburg and Bushbuckridge, it examines how suspicion is constructed and how others are blamed for adverse outcomes. This paper sets a conceptual framework which examines the attribution of blame in contemporary social and political life, the narratives of 45 patients receiving HIV/AIDS, TB or maternal delivery services and those of 63 providers dealing with similar treatments and arranged across a series of facilities, clinics, hospitals and mobile vans were constructed and shared with participants. These narratives form the basis of the results sections which examines suspicions among both providers and patients with the former seeing the latter as having no respect and regard and providing poor care and access to grants. Providers saw themselves as highly stressed but diligent with service challenges being blamed on patient ignorance, unreasonable demands and failure to follow medical advice. The paper ends with a discussion on how to limit mistrust and reduce suspicion through more co-operative provider-patient relations and what this kind of evidence means for decisionmaker

Renormalization Group Approach to Causal Viscous Cosmological Models

The renormalization group method is applied to the study of homogeneous and flat Friedmann-Robertson-Walker type Universes, filled with a causal bulk viscous cosmological fluid. The starting point of the study is the consideration of the scaling properties of the gravitational field equations, of the causal evolution equation of the bulk viscous pressure and of the equations of state. The requirement of scale invariance imposes strong constraints on the temporal evolution of the bulk viscosity coefficient, temperature and relaxation time, thus leading to the possibility of obtaining the bulk viscosity coefficient-energy density dependence. For a cosmological model with bulk viscosity coefficient proportional to the Hubble parameter, we perform the analysis of the renormalization group flow around the scale invariant fixed point, therefore obtaining the long time behavior of the scale factor.Comment: 19 pages. RevTeX4. Revised version. Accepted in Classical and Quantum Gravit

Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂) levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways

Spherically symmetric dissipative anisotropic fluids: A general study

The full set of equations governing the evolution of self--gravitating spherically symmetric dissipative fluids with anisotropic stresses is deployed and used to carry out a general study on the behaviour of such systems, in the context of general relativity. Emphasis is given to the link between the Weyl tensor, the shear tensor, the anisotropy of the pressure and the density inhomogeneity. In particular we provide the general, necessary and sufficient, condition for the vanishing of the spatial gradients of energy density, which in turn suggests a possible definition of a gravitational arrow of time. Some solutions are also exhibited to illustrate the discussion.Comment: 28 pages Latex. To appear in Phys.Rev.

A causal model of radiating stellar collapse

We find a simple exact model of radiating stellar collapse, with a shear-free and non-accelerating interior matched to a Vaidya exterior. The heat flux is subject to causal thermodynamics, leading to self-consistent determination of the temperature $T$. We solve for $T$ exactly when the mean collision time $\tau_{c}$ is constant, and perturbatively in a more realistic case of variable $\tau_{c}$. Causal thermodynamics predicts temperature behaviour that can differ significantly from the predictions of non-causal theory. In particular, the causal theory gives a higher central temperature and greater temperature gradient.Comment: Latex [ioplppt style] 9 pages; to appear Class. Quantum Gra

Acceptable care? Illness constructions, healthworlds, and accessible chronic treatment in South Africa

Achieving equitable access to health care is an important policy goal, with access influenced by affordability, availability, and acceptability of specific services. We explore patient narratives from a 5-year program of research on health care access to examine relationships between social constructions of illness and the acceptability of health services in the context of tuberculosis treatment and antiretroviral therapy in South Africa. Acceptability of services seems particularly important to the meanings patients attach to illness and care, whereas—conversely—these constructions appear to influence what constitutes acceptability and hence affect access to care. We highlight the underestimated role of individually, socially, and politically constructed healthworlds; traditional and biomedical beliefs; and social support networks. Suggested policy implications for improving acceptability and hence overall health care access include abandoning patronizing approaches to care and refocusing from treating “disease” to responding to “illness” by acknowledging and incorporating patients’ healthworlds in patient–provider interactions

Stellar models with Schwarzschild and non-Schwarzschild vacuum exteriors

A striking characteristic of non-Schwarzschild vacuum exteriors is that they contain not only the total gravitational mass of the source, but also an {\it arbitrary} constant. In this work, we show that the constants appearing in the "temporal Schwarzschild", "spatial Schwarzschild" and "Reissner-Nordstr{\"o}m-like" exteriors are not arbitrary but are completely determined by star's parameters, like the equation of state and the gravitational potential. Consequently, in the braneworld scenario the gravitational field outside of a star is no longer determined by the total mass alone, but also depends on the details of the internal structure of the source. We show that the general relativistic upper bound on the gravitational potential $M/R < 4/9$, for perfect fluid stars, is significantly increased in these exteriors. Namely, $M/R < 1/2$, $M/R < 2/3$ and $M/R < 1$ for the temporal Schwarzschild, spatial Schwarzschild and Reissner-Nordstr{\"o}m-like exteriors, respectively. Regarding the surface gravitational redshift, we find that the general relativistic Schwarzschild exterior as well as the braneworld spatial Schwarzschild exterior lead to the same upper bound, viz., $Z < 2$. However, when the external spacetime is the temporal Schwarzschild metric or the Reissner-Nordstr{\"o}m-like exterior there is no such constraint: $Z < \infty$. This infinite difference in the limiting value of $Z$ is because for these exteriors the effective pressure at the surface is negative. The results of our work are potentially observable and can be used to test the theory.Comment: 19 pages, 3 figures and caption

Factors influencing the selection of a university among first-year students – A case of a university of technology in South Africa

The social and political history of South Africa yielded massive transformation in the higher education landscape, including access to education and the merger of universities. Despite the many successes of transformation, it brought with it challenges such as increasing participation, student retention, throughput, and graduation rates; changes in government funding models; declining student subsidies and providing quality education with limited resources. The South African higher education sector is multi-faceted, and students have a wide range of higher education options. This study explored factors influencing decision-making of first-year students when selecting a university. Data was collected from first-year students and employees at a University of Technology. Through in-depth interviews and focus group discussions, the researchers analysed the complex factors that guide students’ decision-making when selecting a university. The findings revealed that factors significantly influencing decision-making on university selection are, the reputation and quality of university programmes offered, response time and support provided by staff; location; and infrastructure and facilities. This research is significant in that it will assist higher education institutions, particularly marketing and communications departments to be more responsive to students’ needs by shifting toward active engagement in its marketing and recruitment approaches to attract, retain, and satisfy students