Bio-artificial liver support system : an evaluation of models used in demonstrating or improving metabolic and clinical efficacy

Acute liver failure (ALF) is a rare but devastating clinical syndrome with multiple causes and a variable course. The mortality rate is high. Orthotopic liver transplantation is the only therapy of proven survival benefit but the limited supply of donor organs, the rapidity of progression and the variable course of ALF limit its use. A need therefore exists for a method to ‘bridge’ patients, that is, provide temporary support, to either the spontaneous regeneration of the innate liver or transplantation. One possibility includes bio-artificial liver support systems (BALSS). This technology is composed of an extracorporeal circulation system incorporating a bioreactor that contains parenchymal liver cells (hepatocytes) to perform the detoxifying, transforming and synthetic properties of a liver. However, the development of a BALSS holds particular challenges. Despite approximately four decades of research, bio-artificial liver (BAL) technology globally remains in a pre-commercial stage. The University of Pretoria (UP) and the Council for Scientific and Industrial Research (CSIR) have developed a BALSS with novel characteristics. These include a computationally optimized radial-flow primary porcine hepatocyte bioreactor perfused with blood plasma, and a perfluorocarbon oxygen carrier which replaces hemoglobin. There are also novel design properties in the circulation system itself. Demonstrating the metabolic and clinical efficacy of a BAL device requires implementing, in vitro (cell biology), in vivo (animal) and mathematical modeling studies. These studies are a formal necessity but are inherently ‘models’ of the in vivo human clinical circumstance. That is, they are limited by their experimentally controlled configuration/s. In investigating these, this thesis firstly provides a foundation by reviewing the clinical and biological context of ALF and BAL technology, then presents and evaluates particular studies/models that have been implemented over several years in the course of the UP-CSIR BAL project. For each section, thoughts and recommendations regarding future work that will facilitate the development of BAL technology are discussed in detail. The thesis is concluded with an evaluation of success and the consensus-agreed requirement of continued research and innovation in the field.Thesis (PhD)--University of Pretoria, 2010.Chemical Engineeringunrestricte

Data-driven Determination of Disease Markers’ Threshold Values in Rot-affected Wine Grapes

Grapevine bunch rot is detrimental to grape and wine quality. Traditionally, detecting and quantifyingthe severity of rot infection is executed visually. This study aimed at defining local, area-specific thresholdvalues of rot-associated disease markers. This is a first step towards making informed decisions aboutthe quality of grapes delivered at winery intake. Viticulturists visually assessed on-vine rot infection innine white wine grape cultivars. Results showed that severity ratings were consistent between assessors.Chemical analyses of the grape must from these assessed samples were done. Multiple factor analysis (MFA)showed that rot severity was positively correlated with glycerol, alcohol, gluconic acid and acetic acidconcentrations. As severity increased, gluconic acid, glycerol, alcohol, Brix, acetic acid and total titratableacidity (TA) concentrations also increased. Following the probability chosen for sensitivity and specificity,grape rot indicators’ threshold values in white grape must are as follow: Alcohol ≥ 0.10 %v/v; acetic acid≥ 0.17 g/L; glycerol ≥ 0.79 g/L; gluconic acid ≥ 0.99 g/L; TA ≥ 8.86 g/L. Statistical determined thresholdvalues differentiating between rot-affected and healthy grape must, would eliminate the subjectivity andbias associated with visual assessments

A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART.

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4.3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals

Age-related reproductive variation in a wild marine mammal population

Life history theory predicts a change in reproduction success with age as energy resources are limited and must be allocated effectively to maximise reproduction and survival. In this study we use three reproductive performance measures; maternal expenditure, offspring weaning mass and first year survival to investigate the role maternal age plays in successful reproduction. Long-term uninterrupted life history data available for Marion Island’s southern elephant seals and mass change estimates from photogrammetry data allow for assessment of age related reproduction performance and trade-offs. Known-aged adult females were photographed for photogrammetric mass estimation (n=29) and their pups weighed at weaning during the 2009 breeding season. Maternal age and proportional mass loss positively influenced pup weaning mass. In turn first year pup return rates (as a proxy for survival) were assessed through the intensive mark-recapture program. Pup survival increased with female age and weaning mass. Pups of young females aged 3 to 6 years have a lower 1st year survival probability compared to pups of older and larger females.http://link.springer.com/journal/300hb201

Observed full blood count and lymphocyte subset values in a cohort of clinically healthy South African children from a semi-informal settlement in Cape Town

Background. The paediatric full blood count and lymphocyte subset reference intervals used by the National Health Laboratory Service (NHLS), South Africa (SA), are taken from two international reference interval publications. Differences in reference intervals suggest that international data sets may not be appropriate for use in SA.Objective. To study immunohaematological values of a group of clinically healthy children from an informal settlement in Cape Town, SA, to assess whether international paediatric reference intervals used by the NHLS are appropriate. Methods. A cross-sectional study of 207 female and 174 male HIV-uninfected children living in an informal settlement in Cape Town was performed. Full blood counts, automated differential counts and lymphocyte subset analysis were done using internationally accepted technologies. Data were categorised by age and reference intervals compiled using medians and 95% confidence intervals (CIs). Gender comparisons were calculated by non-parametric tests. Results. Although median and 95% CI values differed slightly, physiological trends for red cell, platelet, white blood cell differential and lymphocyte subsets were similar to international reference intervals currently in use at the NHLS. Benign ethnic neutropenia was not a significant finding, and gender-specific intervals were not necessary until 12 years of age. Lower overall median values for haemoglobin and haematocrit, and higher median values for mean cell volume and red cell distribution width, were noted. Assessment of haemoglobin, red cell distribution width and calculated Mentzer ratios suggested underlying iron deficiency in 14.2% of participants. Conclusion. Paediatric immunohaematological reference intervals observed in this study are similar to, and support continued use of, international paediatric reference intervals. Underlying iron and related nutritional deficiencies may be contributing to lower haemoglobin levels noted in local children. A larger nationwide study, including all ethnic groups, is recommended.

Spatial variation in female southern elephant seal mass change assessed by an accurate non-invasive photogrammetry method

Physically weighing large marine mammals sequentially over time has presented researchers with a logistical challenge and has severely limited sample sizes. Using a well-established photogrammetry method we developed a simple mathematical method to calculate accurate mass measurements at specific stages in the life cycle of a top marine predator. Female southern elephant seals (n523) at Marion Island were sampled sequentially using photogrammetry and three-dimensional models (based on each photogrammetry project) were built for estimation of body mass. Simple equations were applied to obtain mass at critical instances in their life cycle. Marion Island elephant seal mass data was compared to data obtained from physically weighed elephant seals from King George, South Georgia and Macquarie islands. Females from Marion Island are smaller, but their percentage lactation mass loss is similar to females from these other populations. The similarity of percentage mass loss during lactation between different female populations illustrates the accuracy and practicality of the photogrammetric method over a temporal scale. Photogrammetric mass estimation can be used alongside datasets of physically weighed animals and can greatly benefit ecology and life history studies.http://journals.cambridge.orgam201

Computer simulation and physical phantom models for estimating the dielectric properties of rhinoceros tissue

In vivo and ex vivo sensors have the potential to aid tracking and anti-poaching endeavours and provide new insights into rhinoceros physiology and environment. However, the propagation of electromagnetic signals in rhinoceros tissue is currently not known. We present simulation and agar models of the rhinoceros that allow the investigation of electromagnetic propagation by in vivo and ex vivo devices without the need for surgery. Since the dielectric properties of rhinoceros tissue have not been documented, the conductivity and permittivity of the skin, fat, muscle, blood and other organs are first approximated by means of a meta-analysis that includes animals with similar physical properties. Subsequently, we develop anatomical models that include dermal layers, internal organs and a skeleton. We also develop a flank model that serves as an approximation of the anatomical model in certain situations. These models are used to determine the viability of communication between an in vivo device and an ex vivo device attached to the hind leg of the animal. Two types of antenna (microstrip-fed planar elliptical monopole antenna and printed inverted-F antenna) and three feasible implant locations (back, neck and chest) are considered. In addition to the computer models, phantom recipes using salt, sugar and agar are developed to match the dielectric properties of each tissue type at the industrial, scientific and medical (ISM) frequencies of 403MHz, 910MHz and 2.4GHz. The average error between the measured and theoretically predicted dielectric values was 6.22% over all recipes and 4.49% for the 2.4 GHz recipe specifically. When considering the predicted efficiency of the transmitting and receiving antennas, an agreement of 67.38% was demonstrated between the computer simulations and laboratory measurements using the agar rhinoceros flank models. Computer simulations using the anatomical model of the rhinoceros indicate that the chest is the optimal implant location and that best signal propagation is achieved using the planar inverted-F antenna (PIFA). Using this configuration, the simulations indicate that communication between the implant and an ex vivo device attached to the hind leg is challenging but possible. Furthermore, we find that the inclusion of factors such as the density and temperature of the phantom materials were found to be critical to the achievement of good agreement between practice and simulation.S1 Table. Physical attributes used to determine the degree of similarity between the rhinoceros and various animals.The South African National Research Foundation (NRF) and the South African Centre for Epidemiological Modelling and Analysis (SACEMA).http://www.plosone.orghj2020Paraclinical Science

Longitudinal radiographic study of cranial bone growth in young cheetah

Focal palatitis (also known as focal palatine erosion) is thought to be a developmental disease, specifically of cheetah in captivity raised on a commercial diet. The lack of chewing is thought to cause the mandibular molar to change angulation, contacting the palate and causing the lesions. We followed the development of five captive cheetah cubs, born within 2 weeks of each other, at the same facility. This longitudinal study followed the cubs cephalometrically from 7-months-old to 25-months-old. Of each cub wemade a lateral and dorsoventral radiograph at 7, 13, 20, and 25-months-old. For each radiograph at each age, a predefined series of measurements were made including the angle of the molar. The latter was measured as the angle of the bisecting line running through the apex of the caudal molar root intersecting with a line drawn at the ventral margin of the mandible. The results confirmed that the cheetah skull and neurocranium follows the same neural growth pattern as has been described for other mammalians. Similarly the maxillofacial component follows the same somatic growth as seen in all mammalians excluding humans and non-human primates, where a pubertal growth spurt is present. Finally the angle of the mandibular molar at 7 months differed significantly from the angle at the other ages, however there were no statistical difference in the angulation of the molar after eruption (13 months and older ages). In these five cheetah the lack of chewing (as seen in captivity with a commercial or meat only based diet) did not alter the angulation of the mandibular molar, nor did the mandibular molars super erupt in these patients at 25-months-of-age.https://www.frontiersin.org/journals/veterinary-science#am2020Companion Animal Clinical StudiesMammal Research InstituteStatisticsZoology and Entomolog

Oedipus complex in an Antarctic fur seal pup?

We present the first evidence of a possible case of the Oedipus complex in a nonprimate. An Antarctic fur seal pup, Arctocephalus gazella, unsuccessfully directed what appeared to be copulatory behaviour towards its own mother on several occasions. A herding sub-adult bull chased the pup from the female, which strengthens our suggestion that it was copulatory behaviour we witnessed. This seemed to constitute innocent sexual play with elements of the Oedipus complex rather than coercion because the female was not stressed nor did the pup possess the physical strength to coerce the female.The Department of Science and Technology, through the National Research Foundation (South Africa), provided financial support.http://www.springer.com/life+sci/zoology/journal/1016