Ahead of the Curve

The Robert Bosch Academy in cooperation with the German Commission for UNESCO invited thinkers, activists and representatives of key civil society organisations from around the globe to come together for a workshop in Berlin to explore the 2005 UNESCO Convention on the Protection and Promotion of the Diversity of Cultural Expressions and its relevance for our contemporary world

The relevance of church discipline

In 2004 the General Synod of the Dutch Reformed Church gave an order that an investigation should be done regarding the implementing of church discipline (repeated in 2007 and 2011). There is a need for re-evaluating church discipline and developing a new understanding thereof. This article argues that church discipline is necessary, if the church is serious about protecting the holiness of God and the church. Church discipline should thus be understood, not as punishment, but as brothers and sisters helping each other lovingly to obey God’s orders and to maintain and protect the holiness of God and of His church.http://ojs.reformedjournals.co.za/index.php/stjam2017Dogmatics and Christian Ethic

Facing the stranger in the mirror: Staged complicities in recent South African performances

The staging of complicity has developed into one of the most prevalent trends in recent South Africa theatre. The audience may become aware of their own complicity in injustice, or complicity may feature as a subject to be explored in the play. I will argue that one can identify three broadly defined performance modalities which shape current engagements with complicity. These modalities are identified by the adjectives, 'thick' (as in densely layered, complex, deep), 'reflective' (as in reflecting upon as well as revealing), and 'hard' (in the sense of direct, uncompromising, difficult to penetrate). Rather than signifying distinct categories, these terms are attributed to a cluster of performance dynamics.DHE

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures

Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in South African schoolchildren: Multicentre double-blind randomised placebo-controlled trial (ViDiKids)

Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n=450) nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 vs. placebo for 3 years in HIV- uninfected Cape Town schoolchildren aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH), alkaline phosphatase, C-terminal telopeptide and procollagen type 1 N propeptide. Incidence of fractures was a secondary outcome of the main trial (n=1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (s.d. 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs. placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI - 30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomised to vitamin D vs. placebo (7/755 vs. 10/758 attending at least one follow- up; adjusted odds ratio 0.70, 95% CI 0.27 to 1.85). In conclusion, a 3-year course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizure

Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer

Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition. We found highly significant SNPs in ABCC2, a known carboplatin transporter, associated with carboplatin clearance (asymptotic P = 5.2 × 106, empirical P = 1.4 × 10-5), indicating biological plausibility. We also identified novel SNPs associated with paclitaxel disposition, including rs17130142 with genome-wide significance (asymptotic P = 2.0 × 10-9, empirical P = 1.3 × 10-7). Although requiring further validation, our work demonstrated that GWAS of chemotherapeutic drug disposition can be effective, even in relatively small cohorts, and can be adopted in drug development and treatment programs