School of Anatomical Sciences (Journal Articles)

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A biostatistical support system in health sciences is this sustainable in a resourcerestricted environment
Libhaber, Elena ; Chirwa, Tobias ; Kramer, Beverley
Background: Training in biostatistics is important for strengthening capacity in health research. This is particularly true for Africa, where research output in the health sciences has been low. Training initiatives for the continent are therefore essential. The aim of the present study was to analyse the quality and financial sustainability of the expanded biostatistical support system at a South African health sciences institution between 2013 and 2017. Methods: A cross-sectional investigation of the initiatives created between the years 2013 and 2017 in the University of the Witwatersrand, Faculty of Health Sciences Research Office was undertaken. An assessment of the one-on-one consultations carried out by postgraduate students and staff, financial costs of the support system and the number of postgraduate student graduations were analysed. Results: The number of statistical consultations increased over the period examined. The consultations were highly recommended by the postgraduate students and staff (consulters). A clear rise in the number of Masters and PhD student graduates and an increase in research units were observed from 2013 to 2017, although these cannot be solely associated with the biostatistical support system. The finances for maintaining the support system are cost effective as the number of graduates increases. The total cost to the Research Office is US$ 225 per graduate per annum. Conclusions: The expansion of the biostatistical support system has indirectly contributed to an increased number of graduates and research publication units in the institution. While the current finances support the system, any increases in enrolments or growth in diversification of biostatistical requirements may place a strain on the financial sustainability. This service is of value to developed and developing countries.
Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation
(MDPI, 2021-04-16) Xulu, Kutlwano R.; Augustine, Tanya N.
Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.
Aqueous extract of moringa (Moringa oleifera) leaf (AEMOL) on the growth, sensory and histology parameters of broiler chickens
(ALÖKI Kft, 2020-07) Mbajiorgu, Ejikeme F.; Alabi, O. J.; Ng’Ambi, J. W.
A completely randomized design experiment was used to determine the effects of aqueous extract of Moringa oleifera leaf (AEMOL) on growth, sensory and histology parameters of broiler chickens. Treatment 1 served as the control (antibiotics), Treatment two was given ordinary water (AEMOL0). Treatments 3, 4, 5 and 6 contained 30, 60, 90 and 120 ml of AEMOL per litre of water per day, respectively. Data obtained were analyzed using one-way analysis of variance and mean separation was done using Duncan’s test for multiple comparisons. Results showed that the extract influenced (P < 0.05) the feed intake and water intake at the broiler starter phase WHILE birds on the control diet had higher values. Finisher phase results showed that final weight, weight gain, feed intake, FCR and water intake were influenced (P < 0.05) by the extract with birds treated with 60 ml/l of AEMOL doing better for most parameters except the FCR. All the digestibility and sensory parameters measured were also influenced (P < 0.05) by the extract. However, histological parameters measured were not affected (P > 0.05) by the extract. It could be concluded that the extract inclusion levels up to 90 ml/l can be used to replace antibiotic growth promoter without compromising the advantages of antibiotic growth promoter.
Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data
(BMC, 2018-01) Ceballos, Francisco C.; Hazelhurst, Scott; Ramsay, Michèle
Background: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis. Results: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations. Conclusions: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies
Development of the Wits Face Database: an African database of high-resolution facial photographs and multimodal closedcircuit television (CCTV) recordings [version 1; peer review: 2 approved]
(2021) Bacci, Nicholas; Davimes, Joshua; Steyn, Maryna; Briers, Nanette
Forensic facial comparison is a commonly used, yet under-evaluated method employed in medicolegal contexts across the world. Testing the accuracy and reliability of facial comparisons requires large scale controlled and matching facial image databases. Databases that contain images of individuals on closed-circuit television (CCTV), with matching formal and informal photographs are needed for this type of research. Although many databases are available, the majority if not all are developed in order to improve facial recognition and face detection algorithms through machine learning, with very limited if any measure of standardisation. This paper aims to review the available databases and describe the development of a high resolution, standardised facial photograph and CCTV recording database of male Africans. The database is composed of a total of 6220 standardised and uncontrolled suboptimal facial photographs of 622 matching individuals in five different views, as well as corresponding CCTV footage of 334 individuals recorded under different realistic conditions. A detailed description of the composition and acquisition process of the database as well as its subdivisions and possible uses are provided. The challenges and limitations of developing this database are also highlighted, particularly with regard to obtaining CCTV video recordings and ethics for a database of faces. The application process to access the database is also briefly described.
Forensic facial comparison: current status, limitations, and future directions.
(MDPI, 2021-12-03) Bacci, Nicholas; Davimes, Joshua G.; Steyn, Maryna; Briers, Nanette
Global escalation of crime has necessitated the use of digital imagery to aid the identification of perpetrators. Forensic facial comparison (FFC) is increasingly employed, often relying on poorquality images. In the absence of standardized criteria, especially in terms of video recordings, verification of the methodology is needed. This paper addresses aspects of FFC, discussing relevant terminology, investigating the validity and reliability of the FISWG morphological feature list using a new South African database, and advising on standards for CCTV equipment. Suboptimal conditions, including poor resolution, unfavorable angle of incidence, color, and lighting, affected the accuracy of FFC. Morphological analysis of photographs, standard CCTV, and eye-level CCTV showed improved performance in a strict iteration analysis, but not when using analogue CCTV images. Therefore, both strict and lenient iterations should be conducted, but FFC must be abandoned when a strict iteration performs worse than a lenient one. This threshold ought to be applied to the specific CCTV equipment to determine its utility. Chance-corrected accuracy was the most representative measure of accuracy, as opposed to the commonly used hit rate. While the use of automated systems is increasing, trained human observer-based morphological analysis, using the FISWG feature list and an Analysis, Comparison, Evaluation, and Verification (ACE-V) approach, should be the primary method of facial comparison.
Harnessing Thor’s Hammer: Experimentally induced lightning trauma to human bone by high impulse current.
(Elsevier B.V., 2021) Bacci, Nicholas; Audustine, Tanya N.; Hunt, Hugh G. P.; Nixon, Ken J.; Hoffman, Jakobus; Bam, Lunga; de Beer, Frikkie; Randolph-Quinney, Patrick
Lightning fatality identification relies primarily on soft tissue traumatic pattern recognition, prohibiting cause of death identification in cases of full skeletonisation. This study explores the effects of high impulse currents on human bone, simulating lightning-level intensities and characterising electrically induced micro-trauma through conventional thin-section histology and micro-focus X-ray computed tomography (μXCT). An experimental system for high impulse current application was applied to bone extracted from donated cadaveric lower limbs (n = 22). μXCT was undertaken prior to and after current application. Histological sections were subsequently undertaken. μXCT poorly resolved micro-trauma compared to conventional histology which allowed for identification and classification of lightning-specific patterns of micro-trauma. Statistical analyses demonstrated correlation between current intensity, extent and damage typology suggesting a multifaceted mechanism of trauma propagation - a combination of electrically, thermally and pressure induced alterations. This study gives an overview of high impulse current trauma to human bone, providing expanded definitions of associated micro-trauma.
Supporting early career anatomists: An international challenge
Hartmann, Carol; du Toit, F.; Hutchinson, E.; Pather, N.; Kramer, Beverley
Introduction: The formative years in academia are difficult for early career academics as they transition into their new roles in teaching and research. Ubiquitous changes in health sciences education have compounded this transition for early career anatomists (ECA), who must balance curriculum transformations, research imperatives and administrative responsibilities as they navigate their transition. Support for ECAs is thus important in order to provide a strong pipeline of anatomists for the future of the discipline and its foundational role in the health sciences. Thus, this study investigated the needs of international ECAs with respect to teaching, research and career/professional development in the anatomical sciences. Method: The authors distributed an online survey in 2018 to ECAs of member associations of the International Federation of Association of Anatomists (IFAA). The survey contained both closed and open-ended response questions. Data gathered included ECAs level of academic appointment, training for teaching and nature of support that ECAs may find valuable for their development as anatomists. Frequencies and 95% confidence intervals were calculated and answers to open-response questions were analysed qualitatively. Results: Over 590 respondents from across the globe answered the survey. Requests for training in the clinical relevance and application of anatomical sub-disciplines were frequent. Importantly, support to establish collaborations, mentorship relationships and professional networks were repeatedly requested. Conclusion: In this first ever international survey of ECAs, the needs expressed by respondents indicate the importance of academic and professional development support at both local and global levels. Partnerships between the IFAA, institutions, anatomical and educational associations should create training and mentoring opportunities to smooth the transition into academia for these young academics, which would ensure the future of the discipline and its role in the health sciences.
Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub‑phenotype ex vivo
(Nature, 2020-11-06) Pather, Kyrtania; Augustine, T. N.
Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour subphenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifentherapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.
The diagenetic alterations of historic skeletons from the Crown Mines Cemetery, South Africa
(2023) Lander, Stacey L.; Brits, Desiré ; Hosie, Margot
Human skeletons associated with early gold mining in Johannesburg, South Africa are investigated. An unmarked cemetery was buried beneath a mine dump which resulted in macroscopically stained and poorly preserved bones. Histological assessments were conducted to understand the postmortem treatment of the remains, determine the extent of bone degradation, and understand how this environment affected the bone’s microstructure. Various diagenetic alterations and the general histological index were assessed using normal and polarized light microscopy of thin anterior midshaft femur sections (n = 50). Degradation was identified in the periosteal and endosteal regions, while the intra-cortical region remained well-preserved. Bacterial bioerosion, microcracks, infiltrations, inclusions, and staining were found throughout the sample. Numerous non-Wedl micro-foci of destruction were observed, filled with exogenous material. The degradation suggested that the remains were buried in neutral soil that was subsequently covered by acidic mine dumps which resulted in a corrosive environment. Although the skeletons were poorly preserved, their histological integrity was more promising, especially the intra-cortical area. This is important for future investigations of archaeological bone, as this area can lead to more accurate descriptions of skeletal assemblages. Targeted sampling of this region could produce promising estimates of age, descriptions of pathology, and biomolecular results, which require further study.
The dynamics of pathology dataset creation using urine cytology as an example
McAlpine, Ewen; Michelow, Pamela; Celik, Turgay
Introduction: Dataset creation is one of the first tasks required for training AI algorithms but is underestimated in pathology. High-quality data are essential for training algorithms and data should be labelled accurately and include sufficient morphological diversity. The dynamics and challenges of labelling a urine cytology dataset using The Paris System (TPS) criteria are presented. Methods: 2,454 images were labelled by pathologist consensus via video conferencing over a 14-day period. During the labelling sessions, the dynamics of the labelling process were recorded. Quality assurance images were randomly selected from images labelled in previous sessions within this study and randomly distributed throughout new labelling sessions. To assess the effect of time on the labelling process, the labelled set of images was split into 2 groups according to the median relative label time and the time taken to label images and intersession agreement were assessed. Results: Labelling sessions ranged from 24 m 11 s to 41 m 06 s in length, with a median of 33 m 47 s. The majority of the 2,454 images were labelled as benign urothelial cells, with atypical and malignant urothelial cells more sparsely represented. The time taken to label individual images ranged from 1 s to 42 s with a median of 2.9 s. Labelling times differed significantly among categories, with the median label time for the atypical urothelial category being 7.2 s, followed by the malignant urothelial category at 3.8 s and the benign urothelial category at 2.9 s. The overall intersession agreement for quality assurance images was substantial. The level of agreement differed among classes of urothelial cells - benign and malignant urothelial cell classes showed almost perfect agreement and the atypical urothelial cell class showed moderate agreement. Image labelling times seemed to speed up, and there was no evidence of worsening of intersession agreement with session time. Discussion/conclusion: Important aspects of pathology dataset creation are presented, illustrating the significant resources required for labelling a large dataset. We present evidence that the time taken to categorise urine cytology images varies by diagnosis/class. The known challenges relating to the reproducibility of the AUC (atypical) category in TPS when compared to the NHGUC (benign) or HGUC (malignant) categories is also confirmed.