Showing papers by "University of the Witwatersrand published in 2006"

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

HIV decline associated with behavior change in eastern Zimbabwe.

Abstract: Few sub-Saharan African countries have witnessed declines in HIV prevalence, and only Uganda has compelling evidence for a decline founded on sexual behavior change. We report a decline in HIV prevalence in eastern Zimbabwe between 1998 and 2003 associated with sexual behavior change in four distinct socioeconomic strata. HIV prevalence fell most steeply at young ages-by 23 and 49%, respectively, among men aged 17 to 29 years and women aged 15 to 24 years-and in more educated groups. Sexually experienced men and women reported reductions in casual sex of 49 and 22%, respectively, whereas recent cohorts reported delayed sexual debut. Selective AIDS-induced mortality contributed to the decline in HIV prevalence.

Mortality in the catastrophic antiphospholipid syndrome: Causes of death and prognostic factors in a series of 250 patients

Abstract: Objective. To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). Methods. We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. Results. Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. Conclusion. Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.

Automated image processing method for the diagnosis and classification of malaria on thin blood smears

Abstract: Malaria is a serious global health problem, and rapid, accurate diagnosis is required to control the disease An image processing algorithm to automate the diagnosis of malaria on thin blood smears is developed The image classification system is designed to positively identify malaria parasites present in thin blood smears, and differentiate the species of malaria Images are acquired using a charge-coupled device camera connected to a light microscope Morphological and novel threshold selection techniques are used to identify erythrocytes (red blood cells) and possible parasites present on microscopic slides Image features based on colour, texture and the geometry of the cells and parasites are generated, as well as features that make use of a priori knowledge of the classification problem and mimic features used by human technicians A two-stage tree classifier using backpropogation feedforward neural networks distinguishes between true and false positives, and then diagnoses the species (Plasmodium falciparum, P vivax, P ovale or P malariae) of the infection Malaria samples obtained from the Department of Clinical Microbiology and Infectious Diseases at the University of the Witwatersrand Medical School are used for training and testing of the system Infected erythrocytes are positively identified with a sensitivity of 85% and a positive predictive value (PPV) of 81%, which makes the method highly sensitive at diagnosing a complete sample provided many views are analysed Species were correctly determined for 11 out of 15 samples

The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells.

Abstract: To determine mechanistically how siRNAs mediate transcriptional gene silencing (TGS) in human cells, we have measured histone methylation at targeted promoters, the dependency on active transcription, and whether or not both strands of the siRNA are required for siRNA-mediated TGS. We report here that siRNA treatment increases both H3K9 and H3K27 methylation of the targeted EF1A promoter and that this increase is dependent on nuclear specific delivery of the siRNA. We also find that TGS can be directed by the antisense strand alone, and requires active transcription by RNA polymerase II in human cells as evidenced by sensitivity to α-amanatin. The observation of antisense strand-specific siRNA-mediated TGS of EF1A was substantiated by targeting the U3 region of the HIV-1 LTR/promoter. Furthermore, we show that the antisense strand of siRNA EF52 associates with the transiently expressed Flag-tagged DNMT3A, the targeted EF1A promoter, and trimethylated H3K27. The observations reported here implicate a functional link between siRNA-mediated targeting of genomic regions (promoters), RNA Pol II function, histone methylation, and DNMT3A and support a paradigm in which the antisense strands of siRNAs alone can direct sequence-specific transcriptional gene silencing in human cells.

Nutritional rickets around the world: causes and future directions

Abstract: Introduction: Nutritional rickets has been described from at least 59 countries in the last 20 years. Its spectrum of causes differs in different regions of the world. Methods: We conducted a systematic review of articles on nutritional rickets from various geographical regions published in the last 20 years. We extracted information about the prevalence and causes of rickets. Results: Calcium deficiency is the major cause of rickets in Africa and some parts of tropical Asia, but is being recognised increasingly in other parts of the world. A resurgence of vitamin D deficiency has been observed in North America and Europe. Vitamin D-deficiency rickets usually presents in the 1st 18 months of life, whereas calcium deficiency typically presents after weaning and often after the 2nd year. Few studies of rickets in developing countries report values of 25(OH)D to permit distinguishing vitamin D from calcium deficiency. Conclusions: Rickets exists along a spectrum ranging from isolated vitamin D defic...

Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients

Abstract: Aims Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology with a course and outcome that is largely unpredictable. We evaluated the prognostic role of multiple inflammatory markers in the plasma of a large cohort of African patients with PPCM. Methods and results The study of 100 patients with newly diagnosed PPCM was single-centred, prospective, and longitudinal. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. Inflammatory markers were measured at baseline only. Fifteen patients died. Left ventricular ejection fraction (LVEF) improved from 26.2±8.2 to 42.9±13.6% at 6 months ( P 50%) was only observed in 23%. Baseline levels of C-reactive protein correlated positively with baseline LV end-diastolic (rs=0.33, P =0.0026) and end-systolic (rs=0.35, P =0.0012) diameters and inversely with LVEF (rs=−0.27, P =0.015). Patients who died presented with significantly lower mean EF and higher Fas/Apo-1 plasma values ( P <0.05). Fas/Apo-1 and New York Heart Association functional class (NYHA FC) predicted mortality at baseline. Conclusion Plasma markers of inflammation were significantly elevated and correlated with increased LV dimensions and lower LVEF at presentation. Baseline Fas/Apo-1 and higher NYHA FC were the only predictors of mortality. Normalization of LVEF was only observed in 23% of this African cohort.

Aligned single‐wall carbon nanotube polymer composites using an electric field

Abstract: While high shear alignment has been shown to improve the mechanical properties of single-wall carbon nanotube (SWNT)-polymer composites, this method does not allow for control over the electrical and dielectric properties of the composite and of- ten results in degradation of these properties. Here, we report a novel method to actively align SWNTs in a polymer matrix, which permits control over the degree of alignment of the SWNTs without the side effects of shear alignment. In this process, SWNTs were aligned via AC field-induced dipolar interactions among the nanotubes in a liquid matrix followed by immobilization by photopolymerization under continued application of the electric field. Alignment of SWNTs was controlled as a function of magnitude, frequency, and application time of the applied electric field. The degree of SWNT alignment was assessed using optical microscopy and polarized Raman spectroscopy, and the morphol- ogy of the aligned nanocomposites was investigated by high-resolution scanning electron microscopy. The structure of the field induced aligned SWNTs was intrinsically different from that of shear aligned SWNTs. In the present work, SWNTs are not only aligned along the field, but also migrate laterally to form thick, aligned SWNT percolative col- umns between the electrodes. The actively aligned SWNTs amplify the electrical and dielectric properties of the composite. All of these properties of the aligned nanocomposites exhibited anisotropic characteristics, which were controllable by tuning the applied field parameters. V C 2006 Wiley Periodicals, Inc.* J Polym Sci Part B: Polym Phys 44: 1751-1762, 2006

Living and responding to multiple stressors in South Africa—Glimpses from KwaZulu-Natal

Abstract: Rural, resource-poor communities currently face a number of stressors that curtail livelihood options and reduce overall quality of life. Climate stress in southern Africa could potentially further threaten the livelihoods of such communities. Inappropriate response and adaptation options to risks, including climate stress, could further undermine development efforts in the region. The design and effective implementation of strategies to improve coping and adaptation to possible future risks cannot be undertaken without a detailed assessment of current response options to various risks. By using the Sustainable Livelihoods Framework, this pilot study identifies some of the strategies and constraints to secure livelihoods that are currently being used by small-scale farmers in the Muden area of KwaZulu-Natal. The role and perception of climate risks in relation to a variety of other constraints and risks in the area are also examined. Health status, lack of information and ineffective institutional structures and processes are shown to be some of the key factors aggravating current response options and overall development initiatives with potential negative outcomes for future adaptation to periods of possible heightened climate stress.

Noether-Type Symmetries and Conservation Laws Via Partial Lagrangians

Abstract: We show how one can construct conservation laws of Euler-Lagrange-type equations via Noether-type symmetry operators associated with what we term partial Lagrangians. This is even in the case when a system does not directly have a usual Lagrangian, e.g. scalar evolution equations. These Noether-type symmetry operators do not form a Lie algebra in general. We specify the conditions under which they do form an algebra. Furthermore, the conditions under which they are symmetries of the Euler-Lagrange-type equations are derived. Examples are given including those that admit a standard Lagrangian such as the Maxwellian tail equation, and equations that do not such as the heat and nonlinear heat equations. We also obtain new conservation laws from Noether-type symmetry operators for a class of nonlinear heat equations in more than two independent variables.

A lamprey from the Devonian period of South Africa

Abstract: Lampreys and hagfish are the only remaining jawless vertebrates and are commonly used as surrogate ancestors for comparative research on living jawed vertebrates. Until recently little was known of the evolutionary history of lampreys as the only known fossils were enigmatic examples from the Carboniferous period, around 300 million years ago. Then earlier this year Nature published a report of a fine specimen from the Cretaceous of China that looked very close to modern forms. This is now joined by a well preserved fossil from the Devonian of South Africa, which at about 360 million years old is the oldest known lamprey. It looks slightly different from modern lampreys, but is the same in essentials and differs from the various now-extinct armoured fishes with which it shared the Devonian world. Lampreys are the most scientifically accessible of the remaining jawless vertebrates, but their evolutionary history is obscure. In contrast to the rich fossil record of armoured jawless fishes, all of which date from the Devonian period and earlier1,2,3, only two Palaeozoic lampreys have been recorded, both from the Carboniferous period1. In addition to these, the recent report of an exquisitely preserved Lower Cretaceous example4 demonstrates that anatomically modern lampreys were present by the late Mesozoic era. Here we report a marine/estuarine fossil lamprey from the Famennian (Late Devonian) of South Africa5,6, the identity of which is established easily because many of the key specializations of modern forms are already in place. These specializations include the first evidence of a large oral disc, the first direct evidence of circumoral teeth and a well preserved branchial basket. This small agnathan, Priscomyzon riniensis gen. et sp. nov., is not only more conventionally lamprey-like than other Palaeozoic examples7,8, but is also some 35 million years older. This finding is evidence that agnathans close to modern lampreys had evolved before the end of the Devonian period. In this light, lampreys as a whole appear all the more remarkable: ancient specialists that have persisted as such and survived a subsequent 360 million years.

European geography in a global context from the Vendian to the end of the Palaeozoic

Abstract: A succession of palaeogeographical reconstructions is presented, covering half the globe and the time interval from the latest Proterozoic (Vendian) at 550 Ma to the end of the Palaeozoic (latest Permian) at 250 Ma, mostly at 20 or 30 Ma intervals. The various terranes that today constitute Europe are defined and their margins discussed briefly; these are Gondwana, Avalonia, the Rheno-Hercynian Terrane, the Armorican Terrane Assemblage, Perunica, Apulia, Adria, the Hellenic Terrane (including Moesia), Laurentia, and Baltica. As time elapsed, many of these terranes combined to form first Laurussia and subsequently Pangaea. The further terranes of Siberia and Kara adjoined Europe and were relevant to its Palaeozoic development. Brief sections are included on the individual history and geography of the Vendian and the six Palaeozoic systems, with emphasis on their importance in the building of Europe.

Who can eat information? Examining the effectiveness of seasonal climate forecasts and regional climate-risk management strategies

Abstract: Southern Africa is a region facing multiple stressors, including chronic, recurrent food insecurity and persistent threats of famine. Climate information, including seasonal climate forecasts, has been heralded as a promising tool for early-warning systems and agricultural risk management in southern Africa. Nevertheless, there is concern that climate information, for example climate fore- casts, are not realizing their potential value in the region. The present study considers the actual and potential roles played by climate information in reducing food insecurity in southern Africa from 2 perspectives. The first relates to improved understanding of the contextual environment in which end users operate and use information. Users, including farmers, usually operate in an environment of considerable uncertainty, reacting to and coping with multiple stressors whose impacts are not always clear or predictable. The second perspective relates to improving the current design and vari- ety of mechanisms (e.g. climate outlook forums) for the dissemination and uptake of climate informa- tion. The first relates to improved understanding of the contextual environment in which end users operate and use information. Users, including farmers, usually operate in an environment of consid- erable uncertainty, reacting to and coping with multiple stressors whose impacts are not always clear or predictable. The second perspective relates to improving the current design and variety of mech- anisms (e.g. climate outlook forums) for the dissemination and uptake of climate information. Climate information, it is argued, used in isolation (e.g. in 'stand alone' climate outlook forums) and under- taken in a traditional, linear fashion, where information is moved from producer to user, is divorced from the broader, complex social context in which such information is embedded. This current articulation of climate information flow represents an ineffective means of dealing with climate vari- ability and food security. Alternative modes of interaction (e.g. using existing platforms to 'piggy- back' information or seeking appropriate 'boundary organisations') should be found to sustainably manage climate risks in the region.

Feasibility of structural monitoring with vibration powered sensors

Abstract: Wireless sensors and sensor networks are beginning to be used to monitor structures. In general, the longevity, and hence the efficacy, of these sensors are severely limited by their stored power. The ability to convert abundant ambient energy into electric power would eliminate the problem of drained electrical supply, and would allow indefinite monitoring. This paper focuses on vibration in civil engineering structures as a source of ambient energy; the key question is can sufficient energy be produced from vibrations? Earthquake, wind and traffic loads are used as realistic sources of vibration. The theoretical maximum energy levels that can be extracted from these dynamic loads are computed. The same dynamic loads are applied to a piezoelectric generator; the energy is measured experimentally and computed using a mathematical model. The collected energy levels are compared to the energy requirements of various electronic subsystems in a wireless sensor. For a 5 cm3 sensor node (the volume of a typical concrete stone), it is found that only extreme events such as earthquakes can provide sufficient energy to power wireless sensors consisting of modern electronic chips. The results show that the optimal generated electrical power increases approximately linearly with increasing sensor mass. With current technology, it would be possible to self-power a sensor node with a mass between 100 and 1000 g for a bridge under traffic load. Lowering the energy consumption of electronic components is an ongoing research effort. It is likely that, as electronics becomes more efficient in the future, it will be possible to power a wireless sensor node by harvesting vibrations from a volume generator smaller than 5 cm3.

Review of absorption and adsorption in the hydrogen–palladium system

Abstract: The hydrogen–palladium system has been the subject of much study, both experimentally and computationally. In this review article the authors have set out to draw a comparison between the experimentally determined thermodynamic data for this system and the calculated energies, in order to attempt to bridge the gap between computational chemistry and experimental work and so gain insight into the absorption and adsorption of hydrogen on palladium. Rigorous thermodynamic analysis of the data for the absorption of hydrogen into palladium metal shows that although constant volume measurements have been made, the analysis that has been applied in the literature in several instances is valid only for a constant pressure system. Re-analysis of the data has lead to a heat of formation for β-palladium hydride which is not a function of composition and a weak function of temperature. Values for the internal energy of absorption of −36.7, −35.2 and −34.4 kJ/mol of H 2 were obtained at 0 °C and in the temperature ranges from 200 to 313 °C and from 366 to 477 °C, respectively. There is a good agreement between these values and the calculated values. The implicit assumptions that underpin the integrated form of the Clausius–Clapeyron equation are that an isobaric system is being analyzed, and that the enthalpy is not a function of composition or temperature. Since heat of adsorption is known to be a function of surface coverage and is generally measured in a constant volume system, the application of the integrated Clausius–Clapeyron equation to determine the enthalpy of adsorption as a function of surface coverage has been questioned and an alternative thermodynamic analysis has been proposed that enables one to calculate the differential change in internal energy of adsorption with surface coverage. It has been found that the internal energy of adsorption varies with increasing surface coverage in a similar manner to the way in which internal energy varies as two atoms approach each other. It is noted that the variation in internal energy with surface coverage (0.1 θ The computationally determined energies of adsorption do not reflect this trend and appear to under estimate the electrostatic repulsion (or over estimate the attraction) between gas phase molecules and atoms that are already adsorbed on the surface for this system.

Trust in health care: theoretical perspectives and research needs.

Abstract: Purpose – This paper presents some key theoretical issues about trust, and seeks to demonstrate their relevance to understanding of, and research on, health systems. Although drawing particularly on empirical evidence from low‐ and middle‐income countries (LMICs), the paper aims to stimulate thinking across country settings.Design/methodology/approach – Drawing both on conceptual literature and relevant empirical research from LMICs, the paper presents an argument about the role of trust within key health system relationships and identifies future research needs.Findings – Theoretical perspectives on four questions are first discussed: what is trust and can it be constructed? Why does it matter to health systems? On what is it based? What are the dangers of trust? The relevance of these theoretical perspectives is then considered in relation to: understanding the nature of health systems; issues of equity and justice in health care; and policy and managerial priorities. The identified research needs are i...