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Genetics of suicidality: Genomics as a means of understanding the overlap between suicidal behaviour and schizophrenia
(2026) Mshunqwane, Pheziwe; Ramesar, Rajkumar; Dalvie Shareefa
Introduction: Suicidal behaviour (SB), encompassing attempted suicide and completed suicide,and other related phenotypes, is one of the leading causes of death and disease burden worldwide. Studies have shown that suicide attempt is a major predictor of completed suicide. Moreover, psychiatric disorders such as schizophrenia (SCZ) have been identified as a major risk factor for SB. Both suicide attempt and SCZ have a strong genetic component, with heritability estimates of 17-55% and 41-87%, respectively. Previous studies have demonstrated that while these two phenotypes are genetically distinct, they also show a significant genetic overlap. However, most previous research has been conducted predominantly in individuals of European (EUR) ancestry, with limited data available in the African (AFR) context. The AFR genome has the highest genetic diversity, offering great potential for uncovering novel genetic variants. Therefore, the aim of this study was to investigate the distinct and overlapping genetic architecture of suicide attempt and SCZ in South African cohorts. This was done by: (1) selecting 20 genetic variants previously associated with SB and evaluating their association with suicide attempt in a local cohort; (2) identifying genetic variants associated with SCZ in an indigenous (local) cohort for which whole exome sequencing data was generated; (3) examining the extent of genetic correlation between suicide attempt and SCZ; and (4) assessing whether polygenic risk score (PRS) for suicide attempt can predict SCZ . Methods: A candidate gene-based case-control association study (133 cases and 103 controls) was conducted in a local suicide-attempt cohort. A sequence-based genome-wide association study (seqGWAS) (with whole-exome sequencing data from the Schizophrenia in African Xhosa (SAX) study, (n= 749 cases and 788 controls) was then performed using PLINK. Thereafter, the genetic correlation between suicide attempt and SCZ was assessed using LD Score (LDSC) regression utilizing the latest GWAS summary statistics from the Psychiatric Genetics Consortium (PGC) for both suicide attempt (Ncases= 43,871, Ncontrols= 915,024) and SCZ (Ncases= 76,755, Ncontrols= 243,649). Lastly, polygenic risk scoring was performed using PRS-CSx which allows for trans-ancestry analysis. Association testing was performed in the statistical environment, R. Results: None of the 18 genotyped variants were associated with suicide attempt in the test cohort. The variant rs75837205(p-value = 9.92×-09), located in an intergenic region on chromosome 9, showed genome-wide significance (p-value < 5×10-8). A positive genetic correlation (rg = 0.52, pvalue = 0.0001) between suicide attempt and SCZ was observed, but no association between suicide attempt-PRS and SCZ was detected after correcting for multiple testing. Discussion: The findings reported here reveal novel insights into the genetic architecture of suicide attempt and SCZ in the South African context. Results from this study confirm the genetic overlap between these two traits. This study may offer greater insight into the underlying biological mechanisms involved in suicide attempt and SCZ in the local AFR population. However, further studies with larger sample sizes, and appropriate measurements in populations of AFR ancestry are needed to validate these findings.
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Open Access
Low Rectovaginal and anovaginal fistula repair using a gracilis muscle flap at Groote Schuur Hospital
(2026) Motlaleselelo, Pako; Nel, Daniel
Introduction RVF is a severely debilitating condition with a significant impact on the patient's physical, social, and psychological well-being yet treatment is challenging fraught with high recurrence rates and absence of standardized treatment algorithms. Surgery remains the cornerstone of management despite the absence of a single surgical treatment considered to treat all RVF adequately. Gracilis flap has been used as an attractive option with high success and low complication rates. The body of literature regarding the application of the gracilis flap for addressing rectovaginal fistulas consists of fewer than 40 minor retrospective case series. Furthermore, there is a lack of local data assessing the effectiveness and usefulness of gracilis flaps for addressing RVF in patients from South Africa. Methods In this study, we are aiming to describe our experience in terms of safety and efficacy. After obtaining human research ethics committee approval, a retrospective review of all patients who underwent repair of rectovaginal or anovaginal fistula using gracilis muscle flap between January 2016 and December 2022 was undertaken. Data on patients' demographics, clinical presentation, fistula characteristics, and operative and surgical outcomes were obtained. Clinic follow-up notes were used to look at three months of recurrence after the gracilis flap repair and also three months after stoma closure. Results Over a period of 7 years from 2016 to 2022, six patients underwent retrograde gracilis muscle transposition flap. Patients' age ranged from 19 to 64 years. The main presenting symptoms were passing stool per-vagina. The underlying etiology was an obstetric injury in three patients (50%), foreign body in one patient, post-surgery for rectocele repair in one patient, and the last one of unknown etiology in HIV patient (Table 1). Three patients were found to have RVF with sphincter injury; one was repaired before she was referred to the pelvic floor clinic (patient 4) and the other two referred with concomitant sphincter injury with and without incontinence in patients 5 and 6 respectively. Patient 5 had simultaneous RVF gracilis flap and sphincter injury repair. Patient 6 had a staged procedure, where sphincter repair followed by sacral nerve stimulator was performed before the RVF gracilis 4 flap repair. All patients had previous repair once or twice with either simple repair or advancement flap repair (Table 2). All patients had a covering sigmoid loop colostomy either before or in the same setting with the RVF repair. In this series, the three months success rate was 100%, but both short- and long-term complications were reported in three patients, 50%. The short-term complications were SSI and gracilis flap incomplete necrosis that required debridement under general anaesthesia. Also, two patients developed a parastomal hernia. The mean time from RVF repair to loop colostomy closure was (12.1 months) ranged from 4 to 20 months. Two of the three patients who had stoma closure within one year, had an early closure because they developed a symptomatic parastomal hernia. There were no RVF recurrences reported up to three months after stoma closure (Table 3). Conclusion We concluded that the use of Gracilis flap resulted in very low rates of recurrences but stoma closure rates of 50% at one year thus proving a safe and effective treatment option in patients with complicated rectovaginal fistulas, in addition gracilis flap is an ideal option in patients who have had previous failed attempts at repair.
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Open Access
Being a self of one's own in the social world: developing a Hegelian account of the marginalised self
(2026) Mogomotsi, Olerato Kau; Hull, George
This dissertation provides a novel Hegelian account of what it is to be a marginalized individual in the social world. Here, I defend a metaphysical conception of marginality as being a form of what I term unjust provisionality. To be a marginalized self will be explicated as being unjustly damned to provisionality—where one is marginalized through being precluded from having aspects of one's particular individuality attain actuality in the prevailing social order. Beyond the philosophical treatments of marginality as an ethical issue (of being treated unjustly), I see Hegel as providing us the opportunity to consider the metaphysical aspects of being marginalized—where the social reality of a self and the possibilities of being oneself in the social world are implicated. I develop my account through an extensive exegesis of the Phenomenology of Spirit and the Philosophy of Right. Through this exegesis, I focus on Hegel's articulation of the attainment of Individualität (mired in the context of the dynamic between Sittlichkeit and the Idea) to outline what Hegel takes to be the conditions for the possibility of having a concrete identity in the social world. I end by an extensive defence of the unjust provisionality thesis, by demonstrating why it should be preferred from a conception of marginality inferred from Honneth's critical theory. Finally, I demonstrate that my Hegelian account of marginality has significant advantages over a Butlerian-Foucauldian subjectivation approach to conceptualizing marginality—in that it can account for how power as dominance/subordination produces individuals differentially in relation to power as experiencers of distinct forms of unjust provisionality
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Open Access
Bank provision procyclicality under an expected credit loss model: discretionary behaviour and corporate governance implications
(2026) Mooneeapen, Oren; de Jager, Phillip
Economic cycles, when amplified by their interaction with the banking sector, can transform prosperity into crisis if this interaction is misunderstood and left unchecked. Notably, accounting policy choices can influence this amplification by fuelling excessive credit growth during booms and hindering banks from facilitating recovery in downturns, creating a vicious cycle of instability. In this context, the thesis examines the impact of the IFRS 9 expected credit loss model on the cyclicality of bank loan loss provisions (LLPs), the influence of discretionary behaviours on this cyclicality, and the role of corporate governance in mitigating these influences. It aims to address conflicting findings in the literature by conducting a global study that controls for common factors, providing a consistent analysis and identifying variations by economic classification and region. Fixed-effects panel regression is employed to test the hypotheses of the thesis. Data is sourced from World Bank Open Data and Refinitiv Eikon for the period from 1998 to 2022, with a preference for an extended timeframe, subject to data availability, to capture the fluctuation of LLPs over the business cycle. Analysis beyond traditional frequentist statistical significance testing is done through a more Bayesian approach to inference. The global perspective and more Bayesian approach demonstrate that the extent of LLP procyclicality without IFRS 9 determines the impact of IFRS 9 on LLP procyclicality. IFRS 9 mitigates LLP procyclicality for banks in advanced economies and Europe, while worsening it for banks in emerging and developing economies and Asia. While discretionary behaviours in LLP estimation under IFRS 9 can reduce LLP procyclicality in some contexts, they generally carry the risk of misuse for objectives unrelated to credit risk and worsen LLP procyclicality. There is no robust evidence that current corporate governance mechanisms can mitigate this misuse. This thesis argues that a one-size-fits-all approach through LLPs to reduce the amplification of the boom-and-bust cycles described by the financial instability hypothesis may be ineffective, as the impact of IFRS 9 varies by economic classification, region, and level of procyclicality without IFRS 9. A replicable, transparent, and defendable mechanism is needed to adjust LLPs based on changes in the credit environment and limit potential misuse of discretion. Corporate governance mechanisms have not adequately evolved to address the complexities of discretionary behaviours and associated agency problems under IFRS 9, underscoring the need for their review and update.
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Open Access
Trade liberalisation and wage inequality within the regions of South Africa
(2026) Molokoane, Tshepo Norman; Mateane, Lebogang
This study examines the relationship between trade liberalisation and wage inequality in South Africa's manufacturing sector over the period 1998-2017, using the Stolper-Samuelson theorem as a framework. In this study, we use the autoregressive distributed lag (ARDL) bounds testing technique to estimate the long-run relationship between relative prices, trade openness, labour productivity, human capital, regions, and skill premium. Our main findings show that trade liberalisation has contributed to an increase in wage inequality, predominantly through relative prices, in both the short and long run. We also find that trade openness explains the modest decline in wage inequality, particularly within the coastal region. Additionally, we observe a negative relationship between labour productivity and skill premium across both time frames. The results further reveal that human capital negatively impacts the skill premium but is statistically insignificant in the inland and inland core regions. Regional wage disparities significantly and positively influence the skill premium in the coastal region in the long run, and in the inland region in both the short and long run.