Organised Crime and Law Enforcement in Southern Africa: The Challenges Confronting Research

From the early 1990s onwards, research and policies concerning organised crime in the southern African region have grown apace. But the quest for both quantitative and qualitative research is far from being satisfied. The paper uses an ambitious research project (titled Enhancing Regional Responses to Organised Crime, or EROC) as a case study in order to explore the dynamics which inform and shape research on organised crime from the point of project initiation through to project conceptualisation, data-gathering and analysis, the dissemination of findings, and the formulation of policy recommendations for effective law enforcement. The discussion provides an overview of the many challenges which research on organised crime and law enforcement strategies have to contend with in the southern African region. A critical analysis of the macro- and micro-processes which shape the development of research-based policy interventions in relation to organised crime can contribute to our appreciation of the problem of organised crime itself and of the prospects for police cooperation in the region

A prospective study of paediatric preoperative fasting times at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

Background. Fasting for liquids and solids is recommended prior to procedures requiring anaesthesia, to reduce the risk of pulmonary aspiration. Children often experience excessive fasting, which is associated with negative physiological and behavioural consequences, and patient discomfort. The duration of preoperative fasting in children in South Africa (SA) is unknown.Objectives. To determine compliance with fasting guidelines and fasting times of children prior to elective procedures performed under anaesthesia at a paediatric hospital in Cape Town, SA. The primary focus was fasting for clear liquid. We also intended to identify the most common reasons for prolonged clear liquid fasting.Methods. Over a 7-week period, we prospectively captured fasting times of consecutive patients undergoing elective surgical, medical and radiological procedures at Red Cross War Memorial Children’s Hospital. Measurement outcomes were defined as the period from the last clear liquid, milk or solid feed to the start of anaesthesia. For analysis of compliance with preoperative fasting guidelines, institutional preoperative fasting target limits were established based on the standard 6-4-2-hour guideline.Results. The study included 721 elective paediatric cases. The mean (standard deviation (SD)) fasting time for clear liquids (n=585) was 8.0 (4.8) hours, with an adherence rate of 25.5% (95% confidence interval 22 - 29) to the institutional target of 2 - 4 hours. The mean (SD) fasting times for breastmilk (n=92), formula milk (n=116) and solid feeds (n=560) were 7.1 (2.8), 8.8 (2.8) and 13.9 (3.6) hours, respectively. The factors associated with clear liquid fasting >4 hours were inadequate fasting instructions, poor adherence to fasting orders, procedural delays and fasting to promote theatre flexibility.Conclusions. This study demonstrates that children in an SA hospital experience excessive fasting times prior to elective procedures. To reduce fasting durations and improve the quality of perioperative care, quality improvement interventions are required to create an adaptable fasting system that allows individualised fasting. Improving preoperative fasting times in children is the responsibility of all healthcare professionals in the multidisciplinary management team

The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway

Books

Brain work Brain Work and Mental Activity: Quantitative Studies with Radioactive Tracers. Ed. by N. A. Lassen, D. H. Ingvar, M. E. RaicWe and L. Friberg. Pp. 446. Illustrated. Copenhagen: Munksgaard. 1991.Neuroanatomy Neuroanatomy for Medical Students. 2nd ed. By ]. L. Wilkinson. pp. x + 307. illustrated. Oxford: Butterworth Heinemann. 1992.Atherosclerosis Molecular Biology of Atherosclerosis: Proceedings of the 57th European Atherosclerosis Society Meeting. Ed. by M. J. Halpern. Pp. xv + 662. Illustrated. £45. London: John libbey. 1992.Antibiotics Antibiotic Guidelines. By H. J. Koomhof and L. D. Liebowitz. pp. 122. Pretoria: JL van Schaik. 1991.Reproductive medicine Reproduction, Growth and Development. By A. Negro-Vilar and G. perez-Palacios. Pp. xv + 440. illustrated. $162,50. New York: Raven Press. 1991.Obesity research Progress in Obesity Research 1990. Ed. by Y. Oomura, S. Tarui, S. Inoue and T. Shimazu. Pp. xiii + 688. illustrated. £17,50. London: John Libbey. 1991.Epidemiology Fetal and Infant Origins of Adult Disease. Ed. by D.}. P. Barker. Pp. xv + 343. £30. London: BM}. 1992

The ubiquitin-like modifier FAT10 inhibits retinal PDE6 activity and mediates its proteasomal degradation

The retina-specific chaperone aryl hydrocarbon interacting protein-like 1 (AIPL1) is essential for the correct assembly of phosphodiesterase 6 (PDE6), which is a pivotal effector enzyme for phototransduction and vision because it hydrolyzes cGMP. AIPL1 interacts with the cytokine-inducible ubiquitin-like modifier FAT10, which gets covalently conjugated to hundreds of proteins and targets its conjugation substrates for proteasomal degradation, but whether FAT10 affects PDE6 function or turnover is unknown. Here, we show that FAT10 mRNA is expressed in human retina and identify rod PDE6 as a retina-specific substrate of FAT10 conjugation. We found that AIPL1 stabilizes the FAT10 monomer and the PDE6-FAT10 conjugate. Additionally, we elucidated the functional consequences of PDE6 FAT10ylation. On the one hand, we demonstrate that FAT10 targets PDE6 for proteasomal degradation by formation of a covalent isopeptide linkage. On the other hand, FAT10 inhibits PDE6 cGMP hydrolyzing activity by noncovalently interacting with the PDE6 GAFa and catalytic domains. Therefore, FAT10 may contribute to loss of PDE6 and, as a consequence, degeneration of retinal cells in eye diseases linked to inflammation and inherited blindness-causing mutations in AIPL1

Books

Progress in Medical Virology. Vol. 39. Ed. by J. L. Melnick. Pp. x + 270. Illustrated. £115,70. Basel: S Karger. 1992.Assisted reproduction Micromanipulation of Human Gametes and Embryos. By J. Cohen, H. E. Malter, Beth E. Talansky and J. Grifo. pp. ix + 325. Illustrated. $111,50. New York: Raven Press. 1992.Congenital rubella syndrome EpideIDio1ogy and Infection. Vo!. 107 No. 1. Ed. by J. R. Partison, D. Baxby, J. G. Cruickshank, C. R. Madeley and W. C. Noble. Pp. viii + 239. Illustrated. £25. Cambridge: Cambridge University Press. 1991.Rural and urban hospitals The Hospital in Rural and Urban Districts: Report of a WHO Study Group on the Function of Hospitals at the First Referral Level. pp. vii + 74. SFr.120. Geneva: World Health Organisation. 1992.Perinatology Perinato1ogy: Nestle Nutrition Workshop Series. Vol. 26. Ed. by Erich Saling. pp. xiii + 194. illustrated.$69. New York: Raven Press. 1992.Anaesthetists Five Decades: The South African Society· of Anaesthetists 1943 - 1993. By Nagin Parbhoo. 330 pages and 70 phoros and illustrations. Published by the South African Society of Anaesthetists. Printed by National Book Printers.

Towards Eliminating Bias in Cluster Analysis of TB Genotyped Data

The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naïve methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored

The gynaecological subspecialties: advances in women’s health

Under Professor Dennis Davey’s leadership, the Department of Obstetrics and Gynaecology recognised the need for subspecialist expertise and training. Thus, the gynaecological subspecialties were developed, the first of which was gynaecological oncology. We review the research, and subsequent clinical application, which has evolved from the subspecialist units

Mapping the mechanisms of retinal degeneration caused by mutations in the co-chaperone AIPL1

Mutations in the photoreceptor/pineal-expressed gene AIPL1 cause Leber congenital amaurosis (LCA), the most severe form of childhood inherited retinopathy. AIPL1 is a photoreceptor-specific co-chaperone that interacts with HSP90 via a C-terminal tetratricopeptide repeat (TPR) domain to facilitate the correct assembly and activity of retinal cGMP phosphodiesterase (PDE6). The AIPL1 N-terminal FKBP-like domain interacts directly with the isoprenyl moiety of the PDE6 catalytic subunits. We investigated the functional impact of novel LCA-associated AIPL1 variants. Our data reveal that the relative domain organization and integrity of AIPL1 is important for PDE6-mediated catalysis, with variants mapping to one domain also affecting the activity of the other independently folded domain. The functional assessment and confirmation of likely pathogenic AIPL1 variants is moreover important for the accurate diagnosis and effective triage of patients for AIPL1-targeted gene replacement therapy