Remarkable Rates of Lightning Strike Mortality in Malawi

Livingstone's second mission site on the shore of Lake Malawi suffers very high rates of consequential lightning strikes. Comprehensive interviewing of victims and their relatives in seven Traditional Authorities in Nkhata Bay District, Malawi revealed that the annual rate of consequential strikes was 419/million, more than six times higher than that in other developing countries; the rate of deaths from lightning was 84/million/year, 5.4 times greater than the highest ever recorded. These remarkable figures reveal that lightning constitutes a significant stochastic source of mortality with potential life history consequences, but it should not deflect attention away from the more prominent causes of mortality in this rural area

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission’s Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.info:eu-repo/semantics/publishedVersio

Modelling a tidal turbine in unsteady flow

ABSTRACT A brief review of the literature is provided on the characteristics of marine currents and the approaches used for simulating tidal turbines. The feasibility of using CFD models to simulate time-dependent turbulent flow around a tidal turbine is then explored. Two different approaches for specifying the structure of the turbulent inflow conditions in CFD models are compared: the von Kármán spectral approach and the Synthetic Eddy Method (SEM) of Simulations of the unsteady flow around a tidal turbine, represented here as a simple porous disc, provide some insight into the effect of large-scale flow oscillations on the wake of the turbine. The wake structures obtained from unsteady CFD simulations are compared to those obtained using a steady approach. The results indicate that the presence of large coherent turbulent structures in the incident flow field produces a shorter wake than predicted by steady flow simulations. This work represents the first stage in the development of a unified model which will couple meta-scale simulations of flow in an estuary or complete channel to detailed small-scale simulations of the flow around tidal turbine devices

Modelling a Tidal Turbine in Unsteady Flow

ABSTRACT A brief review of the literature is provided on the characteristics of marine currents and the approaches used for simulating tidal turbines. The feasibility of using CFD models to simulate time-dependent turbulent flow around a tidal turbine is then explored. Two different approaches for specifying the structure of the turbulent inflow conditions in CFD models are compared: the von Kármán spectral approach and the Synthetic Eddy Method (SEM) of Simulations of the unsteady flow around a tidal turbine, represented here as a simple porous disc, provide some insight into the effect of large-scale flow oscillations on the wake of the turbine. The wake structures obtained from unsteady CFD simulations are compared to those obtained using a steady approach. The results indicate that the presence of large coherent turbulent structures in the incident flow field produces a shorter wake than predicted by steady flow simulations. This work represents the first stage in the development of a unified model which will couple meta-scale simulations of flow in an estuary or complete channel to detailed small-scale simulations of the flow around tidal turbine devices

Role of transcriptional and translational gene regulation in the mechanism of doxorubicin cardiotoxicity

Doxorubicin, one of the most widely used and effective anticancer drugs, is limited in its therapeutic use by cardiotoxicity. Multiple hypotheses have been advanced to explain the cardiotoxicity. In this project I utilised novel global genomic analysis of mRNA and miRNA transcription and mRNA translation to investigate the mechanism of doxorubicin cardiotoxicity in vivo. A comparator naphthoquinone was employed in parallel to specifically investigate the potential role of redox activity in the mechanism of cardiotoxicity. For both compounds mouse models were used where cardiac damage was characterised at several dose levels (acute and chronic repeat dosing for 7 weeks). A major transcriptionally and translationally affected pathway was the electron transport chain, this was further confirmed biochemically. These changes were reflected by a rapid loss of ATP and an associated increase in the AMP:ATP ratio and associated activation of AMPK indicating a change in cellular energy dynamics. In tandem mtDNA copy number and caspase 3 were rapidly increased. Comparison of all the data led to the hypothesis that the mechanism of doxorubicin toxicity was via interference with the electron transport chain, possibly through electron shuttling, leading to mitochondrial damage and activation of the intrinsic pathway of apoptosis. In further analysis miRNA alterations associated with the cardiotoxicity of both compounds were investigated. Several miRNAs appeared to be intrinsically involved and one of these, miR-181a was followed up in vitro in HL-1 cells and showed an association with susceptibility to doxorubicin cardiotoxicity. The findings provide a novel insight into doxorubicin cardiotoxicity, through the utilization of genomics and suggest the major mechanism of doxorubicin toxicity is via interference with the electron transport chain, and unrelated to the pharmacological action. These data offer the possibility of molecule alteration to retain the pharmacological profile without the associated cardiotoxicity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Role of transcriptional and translational gene regulation in the mechanism of doxorubicin cardiotoxicity

Doxorubicin, one of the most widely used and effective anticancer drugs, is limited in its therapeutic use by cardiotoxicity. Multiple hypotheses have been advanced to explain the cardiotoxicity. In this project I utilised novel global genomic analysis of mRNA and miRNA transcription and mRNA translation to investigate the mechanism of doxorubicin cardiotoxicity in vivo. A comparator naphthoquinone was employed in parallel to specifically investigate the potential role of redox activity in the mechanism of cardiotoxicity. For both compounds mouse models were used where cardiac damage was characterised at several dose levels (acute and chronic repeat dosing for 7 weeks). A major transcriptionally and translationally affected pathway was the electron transport chain, this was further confirmed biochemically. These changes were reflected by a rapid loss of ATP and an associated increase in the AMP:ATP ratio and associated activation of AMPK indicating a change in cellular energy dynamics. In tandem mtDNA copy number and caspase 3 were rapidly increased. Comparison of all the data led to the hypothesis that the mechanism of doxorubicin toxicity was via interference with the electron transport chain, possibly through electron shuttling, leading to mitochondrial damage and activation of the intrinsic pathway of apoptosis. In further analysis miRNA alterations associated with the cardiotoxicity of both compounds were investigated. Several miRNAs appeared to be intrinsically involved and one of these, miR-181a was followed up in vitro in HL-1 cells and showed an association with susceptibility to doxorubicin cardiotoxicity. The findings provide a novel insight into doxorubicin cardiotoxicity, through the utilization of genomics and suggest the major mechanism of doxorubicin toxicity is via interference with the electron transport chain, and unrelated to the pharmacological action. These data offer the possibility of molecule alteration to retain the pharmacological profile without the associated cardiotoxicity.EThOS - Electronic Theses Online ServiceGBUnited Kingdo