103 research outputs found
The QT interval in lightning injury with implications for the cessation of metabolism hypothesis
An hypothesis is presented to provide an alternative to the Cessation of Metabolism hypothesis often invoked in lightning injury. Cessation of Metabolism has been proposed to explain the observation of good recovery after a prolonged period in cardiac arrest in some lightning injured patients. Reevaluation of EEGs from lightning injured patients show a high incidence of QT prolongation. Reexamination of the cases used to support Cessation of Metabolism also reveals little evidence to justify the hypothesis. The finding of QT prolongation coupled with the hyperadrenergic state said to exist in lightning injury, may promote a state of episodic induction of and recovery from Torsade de Pointes Ventricular Tachycardia (VT). Histological examination of the myocardium supports the new hypothesis. This the first concerted description of lightning injury as one of the general causes of QT prolongation. It appears to occur frequently after lightning injury, is a prerequisite of and predisposes to episodes of Torsade de Pointes VT. These electrocardiographic abnormalities explain Cessation of Metabolism and recognition may change management and lead to greater survival
Studies of in-service and laboratory failures of metal-oxide distribution surge arresters
We describe the findings from tests and inspections of arresters withdrawn from service, the results of laboratory studies with multipulse lightning currents and high temporary over-voltages, and comparisons of in-service and laboratory failure modes. We show that gapped metal-oxide arresters are vulnerable to degradation from moisture ingress in the field and that the main causes of gapless arrester failures in the field and in the laboratory include very high temporary over-voltages and lightning strikes with multiple strokes
A Research Project to Investigate the Impact of Electricity System Requirements On the Design and Optimal Application of the Powerformer (TM)
This paper describes the aims and the methodology of a major collaborative research project between the University of Queensland and Australian and Swedish industry partners, including ABB Corporate Research (Sweden), Alstom Power (Sweden and Australia), PowerLink Queensland, Stanwell Corporation, C S Energy and Tarong Energy. The project is investigating the likely benefits of significance to the Queensland system, which will arise from the optimisation of the new Powerformer technology for the generation of electricity at transmission or sub-transmission voltages, i.e. without step-up transformers
Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes
Introduction: Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large sample of affected individuals. Methods: WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. Results: A genetic diagnosis was obtained for 11.7% (13/111) of individuals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 individuals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). Conclusion: A genetic diagnosis was found in 11.7% of individuals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases. © 2019 The Author
Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.
OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877
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