Paediatrics (RCH) - Research Publications
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ItemNo Preview AvailableInvestigation of oxidative phosphorylation activity and complex composition in mitochondrial disease.(Elsevier, 2023)A multidisciplinary approach to the laboratory diagnosis of mitochondrial disease has long been applied, with crucial information provided by deep clinical phenotyping, blood investigations, and biomarker screening as well as histopathological and biochemical testing of biopsy material to support molecular genetic screening. In an era of second and third generation sequencing technologies, traditional diagnostic algorithms for mitochondrial disease have been replaced by gene agnostic, genomic strategies including whole-exome sequencing (WES) and whole-genome sequencing (WGS), increasingly supported by other 'omics technologies (Alston et al., 2021). Whether a primary testing strategy, or one used to validate and interpret candidate genetic variants, the availability of a range of tests aimed at determining mitochondrial function (i.e., the assessment of individual respiratory chain enzyme activities in a tissue biopsy or cellular respiration in a patient cell line) remains an important part of the diagnostic armory. In this chapter, we summarize several disciplines used in the laboratory investigation of suspected mitochondrial disease, including the histopathological and biochemical assessment of mitochondrial function, as well as protein-based techniques to assess the steady-state levels of oxidative phosphorylation (OXPHOS) subunits and assembly of OXPHOS complexes via traditional (immunoblotting) and cutting-edge (quantitative proteomic) approaches.
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ItemNo Preview AvailableThe Health of People Experiencing Homelessness(Springer International Publishing, 2023)
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ItemNo Preview AvailableMental Health Among Homeless People(Springer International Publishing, 2023)
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ItemInjury(Elsevier, 2017-11-02)Exploration of the consequences of brain insult sustained early in life has a long history, dating back to the 1920s and the seminal works of Lashley (1929), Kennard (1938, 1942), and Hebb (1949), and later comprehensive reviews (e.g., Finger & Stein, 1982; Isaacson, 1975; St James-Roberts, 1975). In this literature, while insults in infancy and early childhood were regarded as qualitatively and quantitatively distinct from those occurring in adulthood, there was little agreement regarding the potential benefits and vulnerabilities of early brain insult.
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ItemSocial cognition in autism spectrum disorder and neurogenetic syndromes(Routledge, 2021)Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterised by impairing social communication deficits and restricted and repetitive behaviours. Over the past few decades, a growing body of research has proposed that social cognitive deficits are a key psychological driver of ASD. In the following chapter, we review evidence for this and show that while social cognitive deficits are common in individuals with ASD, they do not hold clear relationships with ASD symptoms and are not necessary nor sufficient for a diagnosis of ASD. We consider several reasons for this, including the heterogeneity inherent within individuals with ASD, at the symptom, cognitive and aetiological levels. We then discuss the utility of examining ASD and social cognition within syndromic ASD populations which reduce the heterogeneity in the idiopathic population and can be thought of as human ‘genetic models’ of ASD. These syndromic cases of ASD offer a valuable opportunity to elucidate the neurobiological and developmental pathways that lead to both ASD symptoms and aberrant social cognitive processing that are due to a single gene mutation. The possibility of this research to translate into targeted treatments is also explored.
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ItemImpact of early brain insult on the development of social competence(Routledge, 2021)There is growing interest in the social consequences of paediatric brain insult. While current evidence is relatively scarce, findings consistently demonstrate that brain injury in early life confers an elevated risk of social dysfunction across a range of dimensions – social adjustment, social interaction and participation and social cognition. Interactions across these domains and their impact on the child’s other skills is poorly understood. In addition, it appears that the injury-related risk factors that are predictive of cognitive and physical outcomes from early brain insult (injury severity, lesion location, age at insult) are less reliable indicators of social outcomes. Rather, pre-insult child status and environmental factors play a larger role. In particular, social context, family function, child temperament and adjustment to brain insult are all important in determining the child’s social recovery and outcome. Emerging findings from longitudinal studies of childhood ABI show great promise and will facilitate the design of evidence-based interventions in this field. Further, the advent of recent theoretical models of social function and early brain insult, integrating social neuroscience, developmental and developmental psychopathology literatures, provide a strong bio-psychosocial framework for future research.
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ItemNo Preview AvailableWhat the paediatrician needs to know when pandemic influenza arrives in clinical practice(SPRINGER-VERLAG BERLIN, 2008)Avian (H5N1) influenza or “bird ‘flu” has received considerable attention in both the medical literature and the mass media in the last few years. Despite the tabloids’ portrayal of an imminent threat, to date there have been relatively few cases in humans in spite of large numbers of infected poultry (Hien et al. 2004). However, this may be falsely reassuring. Most indications suggest that it is just a matter of time until the next influenza pandemic occurs (Osterholm 2005). In the words of the UK Chief Medical Officer: “most experts believe that it is not a question of whether there will be another severe influenza pandemic but when” (Department of Health 2005). Although experts are agreed that a future influenza pandemic is almost inevitable, its timing is unpredictable and it is uncertain whether the virus responsible will be H5N1 or another, novel, influenza strain (Osterholm 2005). A recent editorial described avian influenza as a “predicament of extraordinary proportions” (Anonymous 2006). The next influenza pandemic will have a dramatic impact on all levels of health care including the everyday work of doctors. This chapter focuses on the clinical aspects of pandemic influenza about which paediatricians need to be familiar.
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ItemNontyphoid Salmonella Disease(Elsevier, 2020)Nontyphoidal Salmonella (NTS) typically causes self-limiting enterocolitis in high-income settings. In sub-Saharan Africa (SSA), however, NTS is a major cause of bloodstream infections, termed invasive nontyphoidal Salmonella (iNTS) disease, causing an estimated 1.9 million cases and 388,000 deaths annually. In SSA, specific clades of Salmonella Typhimurium and Salmonella Enteritidis associated with genomic degradation and multi-drug resistance have emerged. iNTS disease disproportionately affects adults with advanced HIV infection and young children with immature immunity, HIV, and malaria. Children in SSA bear two-thirds of the burden of disease. The non-specific nature of iNTS disease makes it difficult to differentiate from other causes of non-focal febrile illness, and the widespread emergence of multi-drug resistance and emerging cephalosporin resistance presents increasing treatment challenges. iNTS disease causes a large burden of morbidity and mortality in SSA, and there is much that is still unknown about environmental and host reservoirs and transmission of the pathogen and about optimal therapy for this condition. iNTS is also a problem in other resource-limited areas among individuals with HIV, malaria, and compromised or immature immune systems, although SSA accounts for the largest global burden. Vaccine acceleration is a high priority.
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ItemNo Preview AvailablePneumonia(Elsevier, 2017)Pneumonia is an important cause of morbidity and mortality globally. It is the leading cause of death in infants and young children with the majority of these deaths occurring in low income countries. Risk factors affecting incidence and outcome include extremes of age, poor nutrition, immunosuppression, environmental exposures and socioeconomic determinants. Pneumonia can be caused by a wide range of pathogens including bacteria, viruses and fungi, and the etiology varies by epidemiological setting, comorbidities and whether the pneumonia is community-acquired or hospital-acquired. Streptococcus pneumoniae is the major cause of community-acquired bacterial pneumonia while Gram negative bacteria, often resistant to multiple antibiotics, are common causes of hospital-acquired pneumonia and pneumonia in immunosuppressed individuals. Diagnosis is generally clinical and management is based mainly on knowledge of likely causative pathogens as well as clinical severity and presence of known risk factors. Timely and effective antibiotic treatment and oxygen therapy if hypoxemic are critical to patient outcomes. Preventive measures range from improved nutrition and hygiene to specific vaccines that target common causes in children and adults such as the pneumococcal or influenza vaccines.
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ItemNo Preview AvailableCholera(Churchill Livingstone, 2003)