Wayfaring: place and painting in the tropical far north

Walking and painting are investigated in this research to establish a connection with the previously unfamiliar environment of tropical Far North Queensland. This practice-led research project reveals how walking mindfully in nature, and embodied bodily knowledge, can inform works of art. The research is influenced by anthropologist Tim Ingold's (2011) notion that life is a process of wayfaring where we experience the world in terms of movement along a meshwork of trails. Ingold's writing instigated a fundamental shift in my understanding of place. At the beginning of the project I imagined place as a contained or fixed location, however I came to understand place as a sensuous internal/external experience developed over time and along continuous pathways. As a result of engaging with the phenomenology of walking in the natural tropical terrain, I developed a methodology of wayfaring-painting. This new mode of imaginative wayfaring onto the canvas became both a specific mode of creative practice and a means for expressing a wayfaring philosophy in material form on individual canvases and in also the composition and arrangement of the final Wayfaring exhibition. This approach to place-making offers a vision of the tropical landscape that emphasises the significance of the lived experience of contemporary life in the Far North. A central question guides this practice-led research project: How can a body of contemporary visual art evoke the experience of wayfaring in the tropical Far North? Progressive findings are shown in staging exhibitions, culminating in Wayfaring, in which the works of art evoke my phenomenological experience of walking on forest paths and stretches of beach in the Far North. These are the places I've come to know as 'home'. Viewers are invited to take their own wandering journey through the abstracted painted landscapes, which aim to evoke new understandings of the tropical environment and, perhaps, illuminate their own experiences of wayfaring in the world. Wayfaring-painting involves manifesting this sensuous contact in painting. This combination led to new imaginative terrains, revealing deeper understandings of place, self and belonging

Pulfrich's phenomenon in unilateral cataract

AIMS—To determine whether unilateral cataract causes a pathological Pulfrich's phenomenon.
METHODS—29 subjects with unilateral cataract and contralateral pseudophakia were assessed on their ability to perceive the Pulfrich phenomenon. Using a computer generated pendulum image, and graded neutral density filters, a series of forced choice trials were performed in which the subject was required to describe the direction of any apparent pendulum rotation. A pathological Pulfrich effect was said to occur when apparent rotation was perceived in the presence of a zero strength neutral density filter. The size of any pathological Pulfrich effect which was present was quantified by neutralising the perceived pendulum rotation with neutral density filters of varying strength placed before the better seeing eye.
RESULTS—20 out of 29 subjects were able to perceive apparent pendulum rotation when uniocular filtering was performed. In the group (n=12) which was tested both before and after cataract extraction with intraocular lens implantation, a statistically significant pathological Pulfrich effect was demonstrated preoperatively, compared with a group of normal control subjects. This effect was abolished after cataract extraction (p=0.009). The median size of the effect was equivalent to a 0.25 log unit neutral density filter over the non-cataractous eye. The subjects who were unable to perceive the Pulfrich phenomenon at all had a significantly greater difference in the visual acuity of each eye (p=0.045) and significantly worse stereoacuity than those who were able to perceive the effect (p=0.002).
CONCLUSIONS—Unilateral cataract can cause a pathological Pulfrich phenomenon. This finding may explain why some patients with unilateral cataract complain of visual symptoms that are not easily accounted for in terms of visual acuity, contrast sensitivity, or stereoacuity.


Does the Pharmaceutical Sector Have a Coresponsibility for the Human Right to Health?

The highest attainable standard of health is a fundamental human right, which has been part of international law since 1948. States and their institutions are the primary duty bearers responsible for ensuring that human rights are respected, protected, and fulfilled. However, more recently it has been argued that pharmaceutical companies have a coresponsibility to fulfill the human right to health. Most prominently, this coresponsibility has been expressed in the United Nations (UN) Millennium Goal 8 Target 4. “In cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing countries.

Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations

Development of sub-models of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, the advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology (Rowland Yeo et al., 2011; Sayama et al., 2014). In the current study a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment (moderate to severe) on renal drug disposition. Initial PBPK simulations based on changes in glomerular filtration rate (GFR) underestimated the observed reduction in digoxin renal excretion clearance (CLR) in subjects with moderately impaired renal function relative to healthy. Reduction in either proximal tubule cell number or the OATP4C1 abundance in the mechanistic kidney model successfully predicted 59% decrease in digoxin CLR, in particular when these changes were proportional to reduction in GFR. In contrast, predicted proximal tubule concentration of digoxin was only sensitive to changes in the transporter expression/ million proximal tubule cells. Based on the mechanistic modelling, reduced proximal tubule cellularity and OATP4C1 abundance, and inhibition of OATP4C1-mediated transport, are proposed as possible causes of reduced digoxin renal secretion in renally impaired patients

A step too far for teachers?

The recent Green Paper Transforming Children and Young People’s Mental Health Provision contains much that should be lauded. The proposals include designating leads for mental health in schools, integrating mental health and wellbeing into the curriculum, and mental health awareness training for staff. Embedding psychological services in schools could potentially provide a destigmatised, de-medicalised way of supporting children’s mental health needs as they emerge. However, it is essential that the teachers at the forefront of these changes are not forgotten

Knowledge, Attitudes and Perceptions Towards HIV Testing Among IsiXhosa-Speaking Men in The Zithulele Catchment Area of The Rural Eastern Cape Province, South Africa

BACKGROUND South Africa carries the largest burden of Human Immunodeficiency Virus (HIV) in the world, with over 7.9 million people infected and over 70 000 HIV-related deaths in 2019. Men are 25% more likely to die from Acquired Immune Deficiency Syndrome (AIDS) compared to women, even though women are more likely to be infected. Despite these numbers, only 24.1% of HIV-positive men compared to 64.8% of HIV-positive women were aware of their status. Statistics indicate that men in South Africa are not testing for HIV until it is too late. In order to focus efforts on the prevention of HIV transmission, there is a need to understand why men are not accessing HIV testing and treatment services earlier. This study aims to explore the knowledge, attitudes, and perceptions towards HIV testing of isiXhosa-speaking men in the Zithulele catchment area of the rural Eastern Cape. METHODS This was a qualitative study using the phenomenological approach. It was conducted among a purposive sample of isiXhosa-speaking men from the Zithulele catchment area, in the OR Tambo district of the Eastern Cape Province. Ten semi-structured interviews and one focus group were conducted in isiXhosa. Interviews were audiorecorded, transcribed, and translated into English. The interviews were thematically analysed using an inductive approach. RESULTS Participants from the study had a good understanding of HIV and HIV transmission. They perceived HIV infection as a death sentence, a consequence of immoral behaviour and an indication of failure as man. Reluctance to test for HIV was due to the perception that testing hastens the onset of symptoms and death, whereas disclosure of an HIV-positive status was described as difficult due to the fear of stigmatization. Some of the barriers to accessing HIV testing services included masculine norms, the belief that sickness is equated with weakness, a perceived lack of confidentiality at health facilities and how female-dominated clinics were not male-friendly spaces. Suggestions to improve HIV testing among men included improving targeted education, home-based testing services and utilizing traditional meetings to address men. CONCLUSION The findings of this study may suggest that healthy men in the Zithulele catchment area of the rural Eastern Cape are not accessing HIV testing and treatment services. The reasons behind this reluctance include false beliefs around HIV and testing, the fear of discrimination, disruption of masculine norms and reluctance to access care at female-dominated health facilities. Further research is needed to explore ways to reach, educate and encourage men to test earlier for HIV.Thesis (Masters) -- Faculty of Health Sciences, 202

Detection of Botulinum Neurotoxin Serotype B at Sub Mouse LD50 Levels by a Sandwich Immunoassay and Its Application to Toxin Detection in Milk

Botulinum neurotoxin (BoNT), the causative agent of botulism, a serious neuroparylatic disease, is produced by the anaerobic bacterium Clostridium botulinum and consists of a family of seven serotypes (A-H). We previously reported production of high-affinity monoclonal antibodies to BoNT serotype A.Recombinant peptide fragments of the light chain, the transmembrane and receptor-binding domains of the heavy chain of botulinum neurotoxin type B (BoNT/B) were expressed in Escherichia coli as GST-fusion proteins and purified. These proteins were used to immunize BALB/cJ mice for the generation of monoclonal antibodies (mAbs). Antibody-producing hybridomas were detected using either a direct binding ELISA binding to plate-immobilized BoNT/B, or with a capture-capture ELISA whereby the capacity of the antibody to capture BoNT/B from solution was tested. A total of five mAbs were selected, two of which bound the toxin light chain and three bound the receptor-binding domain of BoNT/B heavy chain. MAb MCS6-27 was identified via capture-capture ELISA and was the only mAb able to bind BoNT/B in solution under physiological conditions. MAbs F24-1, F26-16, F27-33 and F29-40 were identified via direct binding ELISA, and were able to capture BoNT/B in solution only in the presence of 0.5-0.9 mM sodium dodecyl sulphate (SDS). MAb MCS6-27 and an anti-BoNT/B polyclonal antibody were incorporated into a sandwich ELISA that did not require SDS.We report here the generation of monoclonal antibodies to serotype B and the subsequent development of a sensitive sandwich immunoassay. This immunoassay has a detection limit of 100 fg BoNT/B, fifty times more sensitive than the mouse bioassay detection limit of 5 pg BoNT/B. Additionally, this assay detected as little as 39 pg/mL of toxin in skim, 2% and whole milk

Toward systems-informed models for biologics disposition: covariates of the abundance of the neonatal Fc Receptor (FcRn) in human tissues and implications for pharmacokinetic modelling

Biologics are a fast-growing therapeutic class, with intertwined pharmacokinetics and pharmacodynamics, affected by the abundance and function of the FcRn receptor. While many investigators assume adequacy of classical models, such as allometry, for pharmacokinetic characterization of biologics, advocates of physiologically-based pharmacokinetics (PBPK) propose consideration of known systems parameters that affect the fate of biologics to enable a priori predictions, which go beyond allometry. The aim of this study was to deploy a systems-informed modelling approach to predict the disposition of Fc-containing biologics. We used global proteomics to quantify the FcRn receptor [p51 and β2-microglobulin (B2M) subunits] in 167 samples of human tissue (liver, intestine, kidney and skin) and assessed covariates of its expression. FcRn p51 subunit was highest in liver relative to other tissues, and B2M was 1–2 orders of magnitude more abundant than FcRn p51 across all sets. There were no sex-related differences, while higher expression was confirmed in neonate liver compared with adult liver. Trends of expression in liver and kidney indicated a moderate effect of body mass index, which should be confirmed in a larger sample size. Expression of FcRn p51 subunit was approximately 2-fold lower in histologically normal liver tissue adjacent to cancer compared with healthy liver. FcRn mRNA in plasma-derived exosomes correlated moderately with protein abundance in matching liver tissue, opening the possibility of use as a potential clinical tool. Predicted effects of trends in FcRn abundance in healthy and disease (cancer and psoriasis) populations using trastuzumab and efalizumab PBPK models were in line with clinical observations, and global sensitivity analysis revealed endogenous IgG plasma concentration and tissue FcRn abundance as key systems parameters influencing exposure to Fc-conjugated biologics