Sudden unexpected death in infants: a forensic genetic investigation in a South African cohort

Sudden unexpected death in infants (SUDI) is a devastating event, and unfortunately occurs frequently in South Africa. The emerging molecular autopsy has added value to SUDI investigations by revealing genetic variants which contributed to their demise. Motivated by the value of this concept to family members as well as the limited research of SUDI locally, the aim of this study was to explore molecular autopsies in the medico-legal investigation of SUDI cases in South Africa. A 5-year retrospective study of 1.199 SUDI admissions to Salt River Mortuary, Cape Town showed that 110 (9.%) cases were still under investigation, while most had infectious causes of death. An ethical framework was established and used to prospectively recruit 201 SUDI cases from Salt River Mortuary. A pilot quality assessment of DNA from blood, buccal cells and formalin fixed paraffin embedded tissue motivated the prospective collection of blood samples. Three variants previously associated with the risk of infections (IL-6 rs1800795.G>C; TNF-α rs1800629.G>A; TLR4 rs4986790.A>G) were genotyped in the sampled cohort. The allele frequency data generated suggested a possible association between each of these variants and an infection-related cause of death in SUDI. Targeted genotyping of candidate variants revealed several pathogenic mutations, including a twin who was homozygous T/T for a founder mutation, GALT rs111033690.C>G/T, causative of galactosaemia (previously undiagnosed). Follow up with the family revealed that the other twin had subsequently demised. Additionally, 43 genes previously associated with cardiac arrhythmias, were sequenced in a subset of cases (n.=.19) and parental samples. Putative pathogenic variants were identified in four infants, and four additional novel variants were found. Lastly, using a hypothesis-free approach, clinical exome sequencing was performed on two cases, which suggested one infant was immune-compromised and the second may have had bronchopulmonary dysplasia. The findings in this study highlight possible new candidate variants to assess in SUDI cases, and has directly contributed to the development of a molecular autopsy which is locally relevant. It is evident that until newborn screening becomes routine and accessible in South Africa, molecular autopsies should include testing for inherited metabolic disorders, as it holds potential to save lives

Returning to Jamais Vu: Uncanny Encounters in the Live Art Archive and in the Flesh

This paper explores returning to a performance, again and again, over an extended time frame, to re-imagine and re-view the piece. It focuses on a performance entitled Jamais Vu (2005–2007) by live artist Anne Seagrave. I analyse my personal encounter with the work over time, arguing for the significance of this durational approach, and of this artist/artwork for performance philosophy. I return to the work via writing/rewriting and performing/re-performing based on archival documents and embodied memory.

Representation and identity in contemporary performance.

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN020309 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Novel CYP2E1 haplotype identified in a South African cohort

Alcohol abuse accounts for approximately 2.5 million deaths annually and is the third highest risk factor for disease and disability. Alcohol is metabolised by polymorphic enzymes and the status of an individual with respect to alcohol metabolising enzymes may have forensic relevance in post-mortems. Baseline frequencies of gene variants involved in alcohol metabolism need to be established to aid the identification of suitable population-specific polymorphisms to genotype during molecular autopsies. The principal alcohol metabolising enzymes include alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1). Six single nucleotide polymorphisms (SNPs) - rs1229984G>A and rs2066702C>Tin ADH1B, rs671G>A in ALDH2, and rs3813867G>C, rs2031920C>T and rs6413432T>A in CYP2E1 - were genotyped in 150 individuals from four South African populations: Xhosa, Zulu, South African white and South African coloured. Allele frequencies for each SNP in the four population groups were 0-10% for rs1229984A, 2-12% for rs2066702T, 0-2% for rs671A, 1-4% for rs3813867C, 0-1% for rs2031920T and 3-15% for rs6413432A. Haplotype analysis revealed a novel combination of three SNPs in CYP2E1 whose effects on alcohol metabolism need further investigation. Establishment of baseline frequencies adds to our knowledge of genetic variation in alcohol metabolising enzymes and additional research is required to determine the functional significance of this novel CYP2E1 haplotype

Bodies without names: A retrospective review of unidentified decedents at Salt River Mortuary, Cape Town, South Africa, 2010 - 2017

Background. Decedents who remain unidentified and/or unclaimed following postmortem investigations are an international occurrence. Salt River Mortuary (SRM), one of the largest and busiest mortuaries in Cape Town, South Africa, also experiences this burden; however, little is known about the nature of these cases.Objectives. To review all cases admitted to SRM between 1 January 2010 and 31 December 2017 (n=26 960), with the objectives of quantifying the number of decedents who remained unidentified, and to better understand circumstances surrounding death and the identification methods that were attempted.Methods. Data pertaining to unidentified cases were collected from mortuary burial records and medicolegal case files. Data were analysed using Microsoft Excel 2013 (Microsoft, USA).Results. Over the 8-year period, 2 476 cases (mean 9.2% of caseload per annum) admitted to SRM remained unidentified. Bodies underwent an autopsy after a median of 3 days after a death declaration. However, in cases of decomposition, skeletonisation or other physical inhibitors of visual identification (n=345; 14.1%), the time between death and autopsy was undetermined owing to the overall lack of entomology analyses. Approximately 56.9% (n=1 408) of cases were between 20 and 50 years of age, and were predominantly males (78.7%). Unnatural injury-related deaths accounted for 32.4% of unidentified deaths, with firearms, assault and stabbings contributing approximately one-third each. With regard to identification attempts, forensic anthropology was requested in only 1.5% of these cases, and DNA analysis appeared to be used in only 23.6% of cases. Data pertaining to secondary identifiers, forensic odontology and fingerprint analyses were not formally recorded.Conclusions. The relatively short time interval between death declaration and postmortem examination suggests that DNA analysis should be more regularly utilised. Furthermore, it is urged that other ancillary investigations should be more regularly employed; that there is a greater collaboration between stakeholders and identification attempts; and that results are centrally recorded

The unseen and unacceptable face of digital libraries

The social and organizational aspects of digital libraries are often overlooked but this paper reviews how they can affect users' awareness and acceptance of digital libraries. An analysis of research conducted within two contrasting domains (Clinical and Academic) is presented which highlights issues of user interactions, work practices and the organizational social structures. The combined study comprises an analysis of 98 in-depth interviews and focus groups with lecturers, librarians and hospital clinicians. The importance of current and past roles of the library, and how users interacted with it, are revealed. Web-based digital libraries, while alleviating most library resource and interaction problems, require a change in librarians' and DL designers' roles and interaction patterns if they are to be implemented acceptably and effectively. Without this role change, users will at best be unaware of these digital resources and at worst feel threatened by them. The findings of this paper highlight the importance on DL design and implementation of the social context and supporting user communication (i.e. collaboration and consultation) in their information search and usage activities

Dragging Affordances

Panel discussion with Elly Clarke, Ofri Cnaani, Adrian Heathfield, and Emily Rosamon