Cerebral Palsy and Criteria Implicating Intrapartum Hypoxia in Neonatal Encephalopathy – An Obstetric Perspective for the South African Setting

The science surrounding cerebral palsy indicates  that it is a complex medical condition with multiple contributing variables and factors, and causal pathways are often extremely difficult to delineate. The pathophysiological processes are often juxtaposed on antenatal factors, genetics, toxins, fetal priming, failure of neuroscientific autoregulatory mechanisms, abnormal biochemistry and abnormal metabolic pathways. Placing this primed compromised compensated brain through the stresses of an intrapartum process could be the final straw in the pathway  to brain injury and later CP.  It is thus simplistic to base causation of cerebral palsy on only an intrapartum perspective with radiological ‘confirmation’, as is often the practice in medicolegal cases in South African courts. The present modalities (MRI and CTG when available) that retrospectively attempt to determine causation in courts are inadequate when used in isolation. Unless a holistic scientific review of the case including all contributing clinical factors (antepartum, intrapartum and neonatal), fetal heart rate monitoring, neonatal MRI if possible (and preferred) or late MRI, and histology (placental histology if performed) are taken into account, success for plaintiff or defendant currently in a court of law will depend on eloquent legal argument rather than true scientific causality. The 10 criteria set out in this document to implicate acute intrapartum hypoxia in hypoxic ischaemic encephalopathy/neonatal encephalopathy serve as a guideline in the medicolegal setting

On a new class of tests for the Pareto distribution using Fourier methods

We propose new classes of tests for the Pareto type I distribution using the empirical characteristic function. These tests are $U$ and $V$ statistics based on a characterisation of the Pareto distribution involving the distribution of the sample minimum. In addition to deriving simple computational forms for the proposed test statistics, we prove consistency against a wide range of fixed alternatives. A Monte Carlo study is included in which the newly proposed tests are shown to produce high powers. These powers include results relating to fixed alternatives as well as local powers against mixture distributions. The use of the proposed tests is illustrated using an observed data set

Clinical practice

Basal ganglia and thalamus (BGT) hypoxic-ischaemic brain injury is currently the most contentious issue in cerebral palsy (CP) litigation in South Africa (SA), and merits a consensus response based on the current available international literature. BGT pattern injury is strongly associated with a preceding perinatal sentinel event (PSE), which has a sudden onset and is typically unforeseen and unpreventable. Antepartum pathologies may result in fetal priming, leading to vulnerability to BGT injury by relatively mild hypoxic insults. BGT injury may uncommonly follow a gradual-onset fetal heart rate deterioration pattern, of duration ≥1 hour. To prevent BGT injury in a clinical setting, the interval from onset of PSE to delivery must be short, as little as 10 - 20 minutes. This is difficult to achieve in any circumstances in SA. Each case needs holistic, multidisciplinary, unbiased review of all available antepartum, intrapartum and postpartum and childhood information, aiming at fair resolution without waste of time and resources.

Adolescent male chimpanzees (Pan troglodytes) form social bonds with their brothers and others during the transition to adulthood

Social relationships play an important role in animal behavior. Bonds with kin provide indirect fitness benefits, and those with nonkin may furnish direct benefits. Adult male chimpanzees (Pan troglodytes) exhibit social bonds with maternal brothers as well as unrelated adult males, facilitating cooperative behavior, but it is unclear when these bonds develop. Prior studies suggest that social bonds emerge during adolescence. Alternatively, bonds may develop during adulthood when male chimpanzees can gain fitness benefits through alliances used to compete for dominance status. To investigate these possibilities and to determine who formed bonds, we studied the social relationships of adolescent and young adult male chimpanzees (N = 18) at Ngogo in Kibale National Park, Uganda. Adolescent male chimpanzees displayed social bonds with other males, and they did so as often as did young adult males. Adolescent and young adult males frequently joined subgroups with old males. They spent time in proximity to and grooming with old males, although they also did so with their age peers. Controlling for age and age difference, males formed strong association and proximity relationships with their maternal brothers and grooming relationships with their fathers. Grooming bonds between chimpanzee fathers and their adolescent and young adult sons have not been documented before and are unexpected because female chimpanzees mate with multiple males. How fathers recognize their sons and vice versa remains unclear but may be due to familiarity created by relationships earlier in development.Adolescent male chimpanzees, by age 12 years, have as many strong grooming bonds as do young adults.Research HighlightsAdolescent male chimpanzees form social bonds with other males.Bonds were common between unrelated males, but frequent with maternal brothers, peers, old males, and fathers.Fathers may be important for male chimpanzees transitioning to adulthood.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153616/1/ajp23091.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153616/2/ajp23091_am.pd

International Paediatric Mitochondrial Disease Scale

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International Paediatric Mitochondrial Disease Scale

Objective: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study. Methods: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6–16 years) from five different expert centres from four different continents were evaluated in this study. Results: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23–0.99). Conclusion: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study

\ua9 2024, The Author(s).Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. Methods: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. Results: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067–0.00084%. Conclusions: This study reveals the first extensive genotype–phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population

The Lingering Environmental Impact of Repressive Governance: The Environmental Legacy of the Apartheid Era for the New South Africa

This article aims to explore the historical link between contemporary environmental problems and the environmental, economic and political policies of the apartheid government. The analysis draws on an examination of the detrimental environmental impacts of the apartheid era and how international isolation impacted on governmental environmental management in the country, before turning attention to the way in which the ANC government has managed the South African natural and human environments in the period after 1994. The article shows that despite many important new developments since 1994, that there are high levels of continuity between the environmental management practices of the old and the new regimes. This state of affairs negatively impacts on the ability of the ANC government to provide every South African citizen with the clean and safe environment guaranteed to all within the 1996 Bill of Rights.This article also appeared unchanged as a chapter in the following edited collection: Jan Oosthoek and Barry K. Gills (eds), _The Globalization of Environmental Crisis_ (Abingdon: Routledge, 2008), pp. 109-120

Framework for knowledge asset management in community projects in higher education institutions

Innovation in education encourages stakeholders to explore and apply different ways of looking at problems and solving them. Large-scale community projects (LSCPs) in a higher education institution (HEI), provide an ideal environment for combining curriculum outcomes, education innovation, real-world engagement and knowledge assets. However, current research that focuses on knowledge asset management in innovative learning is limited, and this study aims to contribute a holistic approach for managing knowledge assets in this context. In this study, we designed a knowledge asset management framework for LSCPs in higher education taking cognisance of innovative educational model characteristics. We applied the framework by mapping it to a community project module from an HEI using the elements of the framework as a guide. By using the knowledge asset management framework for LSCPs in higher education, an HEI can ensure that their community module enables strong support to the community, that students’ knowledge and skills are enhanced and that all new knowledge assets created during the project delivery, are captured and stored using innovative technology sets.http://link.springer.combookseries/558hj2020Informatic

Emotional and Functional Challenge in Core and Avant-garde Games

Digital games are a wide, diverse and fast developing art form, and it is important to analyse games that are pushing the medium forward to see what design lessons can be learned. However, there are no established criteria to determine which games show these more progressive qualities. Grounded theory methodology was used to analyse language used in games reviews by critics of both 'core gamer' titles and those titles with more avant-garde properties. This showed there were two kinds of challenge being discussed — emotional and functional which appear to be, at least partially, mutually exclusive. Reviews of 'core' and 'avant-garde' games had different measures of purchase value, primary emotions, and modalities of language used to discuss the role of audiovisual qualities. Emotional challenge, ambiguity and solitude are suggested as useful devices for eliciting emotion from the player and for use in developing more 'avant-garde' games, as well as providing a basis for further lines of inquiry