26 research outputs found

    Regional-Scale Forecasting for Coastal Storm Hazard Early Warning Systems

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    Sandy beach and dune systems often provide coastal communities with the first line of defence from the impacts of extreme storm events. During a storm’s approach, communities have a crucial opportunity to take preemptive actions to minimise the social, economic, and environmental impacts of the storm. Predicting coastal storm hazards, especially at the regional scale, however, is challenging due to the complexities of the hydrodynamic and morphodynamic processes occurring on erodible coastlines in high wave energy conditions. This thesis examines the nature and severity of coastal storm hazards and investigates approaches to effectively forecast these hazards for operational Early Warning Systems (EWSs). First, a conceptual framework for classifying coastal storm hazards is introduced. The Storm Hazard Matrix presents an integrated approach to categorising coastal flooding and beach erosion hazards. The Flooding Hazard Scale is based on the Storm Impact Scale first proposed by Sallenger (2000). The new Erosion Hazard Scale is based on several different morphological changes in beaches due to storms, including changes in beach width and dune erosion. The framework is demonstrated on two contrasting extreme storm events and successfully distinguishes between the severity of localised coastal flooding and/or beach erosion hazards. The enhanced insight provided by using the framework has the potential to be especially valuable for EWS applications. Next, a simple classification approach to forecast coastal storm erosion hazards based on the Erosion Hazard Scale is developed based on dune impact exposure (Larson et al., 2004), cumulative storm wave energy (Dolan and Davis, 1992; Harley et al., 2009) and the Dune Stability Factor (Armaroli et al., 2012). Two coastal change datasets are used to investigate the performance of the approach in terms of temporal variability and spatial variability. In each dataset, all events or locations of significant erosion impacts are correctly identified. The approach tended to be conservative with few false alarms (and no misses), demonstrating its predictive capability with limited input data and computational resources. Finally, machine learning techniques are investigated to leverage the increasing availability of coastal topographic and hydrodynamic data. A gradient boosted random forest ensemble model is trained using an extreme coastal storm erosion hazard dataset. The model is demonstrated by hindcasting regional-scale coastal storm erosion hazards over a period of 5 years. Additionally, an investigation of the training data requirements and interpretation of the model feature importance characteristics are also performed. The findings and insights discussed in this thesis represent the state-of-the-art approaches to forecasting coastal storm hazards at the regional scale and can serve to inform the implementation of future EWSs

    Effects of Interferon-α/β on HBV Replication Determined by Viral Load

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    Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low

    The Glycan Shield of HIV Is Predominantly Oligomannose Independently of Production System or Viral Clade

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    The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide and vaccine design. The extent of cross-clade conservation of HIV oligomannose glycans is therefore a critical consideration for the development of HIV prophylaxes. We measured the oligomannose content of virion-associated gp120 from primary virus from PBMCs for a range of viral isolates and showed cross-clade elevation (62–79%) of these glycans relative to recombinant, monomeric gp120 (∼30%). We also confirmed that pseudoviral production systems can give rise to notably elevated gp120 oligomannose levels (∼98%), compared to gp120 derived from a single-plasmid viral system using the HIVLAI backbone (56%). This study highlights differences in glycosylation between virion-associated and recombinant gp120

    Community paramedic point of care testing: validity and usability of two commercially available devices

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    Abstract Background Community Paramedics (CPs) require access to timely blood analysis in the field to guide treatment and transport decisions. Point of care testing (POCT), as opposed to laboratory analysis, may offer a solution, but limited research exists on CP POCT. The purpose of this study was to compare the validity of two devices (Abbott i-STAT® and Alere epoc®) by CPs in the community. Methods In a CP programme responding to 6000 annual patient care events, a split sample validation of POCT against traditional laboratory analysis for seven analytes (sodium, potassium, chloride, creatinine, hemoglobin, hematocrit, and glucose) was conducted on a consecutive sample of patients. The difference of proportion of discrepant results between POCT and laboratory was compared using a two sample proportion test. Usability was analysed by survey of CP experience, a linear mixed effects model of Systems Usability Scale (SUS) adjusted for CP clinical and POCT experience, an expert heuristic evaluation of devices, a review of device-logged errors, and coded observations of POCT use during quality control testing. Results Of 1649 episodes of care screened for enrollment, 174 required a blood draw, with 108 episodes (62.1%) enrolled from 73 participants. Participants had a mean age of 58.7 years (SD16.3); 49% were female. In 4 of 646 (0.6%) comparisons, POCT reported a critical value but the laboratory did not; with no statistically significant (p = 0.323) difference between i-STAT® (0.9%;95%CI:0.0,1.9%) compared with epoc® (0.3%;95%CI:0.0,0.9%). There were no instances of the laboratory reporting a critical value when POCT did not. In 88 of 1046 (8.4%) comparisons the a priori defined acceptable difference between POCT and the laboratory was exceeded; occurring more often in epoc® (10.7%;95%CI:8.1,13.3%) compared with i-STAT® (6.1%;95%CI:4.1,8.2%)(p = 0.007). Eighteen of 19 CP surveys were returned, with 11/18 (61.1%) preferring i-STAT® over epoc®. The i-STAT® had a higher mean SUS score (higher usability) compared with epoc® (84.0/100 vs. 59.6/100; p = 0.011). There were no statistically significant differences in device logged errors between i-STAT® and epoc® (p = 0.063). Conclusions CP programmes can expect clinically valid results from POCT. Device usability assessments should be considered with any local implementation as the two POCT systems have different strengths
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