19 research outputs found
Intelligent Equalisation Principles and Techniques for Minimising Masking when Mixing the Extreme Modern Metal Genre.
No full textThe intensity, complexity and energy of performance, combined with the power and density of the tones involved are characteristics of the extreme metal genre. These characteristics present numerous problems when striving to achieve the clarity, definition and hyper-realism of performance required for this genres production. Avoiding masking in a mix is a fundamental
aspect of clarity, definition, intelligibility and perceived loudness and due to the fact that masking especially occurs in a dense mix, and is more pronounced in low frequencies, is particularly applicable to mixing the downtuned extreme metal genre. Masking in simple terms is the ability of frequencies of one sound to obscure or inhibit (i.e. mask) the frequencies of
another sound. This paper will draw upon the first author’s eight years of experience producing within the metal genre, including releases through Sony and Universal and working with the likes of Colin Richardson and Andy Sneap
Determining potential for pollutant impacts in dynamic coastal waters: comparing morphological settings
No full textThe coastal focus and beach culture of Australia’s population in general, and the people of New South Wales in particular, mean that coastal systems are both highly prized and subjected to great pressures. The vast majority of the wastewater generated by the 7.3 million people of New South Wales is discharged directly to the ocean. The dispersion and fate of waterborne pollutants and their potential to impact coastal ecosystems are fundamentally determined by the dynamics of the coastal boundary layer (CBL). This turbulent interface between the coastline and the deep oceans is defined and classified for the first time in this thesis. Coastal morphologies and changes in the orientation of the coastline promote turbulence and strong gradients with extreme variability and heterogeneity over a broad range of scales. Conceptual models are presented to characterise New South Wales coastal boundary layer processes.
The broad aims of this thesis are to investigate the coastal boundary layer processes that affect dispersal and advection of pollutants, and to develop conceptual models and tools to facilitate coastal management.
Remote sensed ocean colour and sea surface temperature observations define meso-scale CBL phenomena, and this study demonstrates their application to support management decisions in relation to marine algal (phytoplankton) blooms. However, considerable scope exists to improve regional algorithms to deliver better ocean colour products for the optically complex (Case 2) waters of the inner coastal boundary layer.
Past failures to consider the CBL (morphological) settings of pollutant discharges to coastal waters have led to inefficient pollutant discharge systems and potential environmental impacts. Two case studies, investigate the principal forcing mechanisms and demonstrate the importance of morphology in controlling the dispersion and retention times of pollutants.
The first case study is focused on Sydney coastal waters where pollutant loadings are greater in magnitude and different in character than elsewhere in New South Wales. Here population pressures generate large wastewater loadings but the distances to offshore discharge locations are large compared to the scale of coastal roughness (headlands and bays) and the water is deep, thus reducing the risk of local retention of pollutants and increasing the potential for rapid dilution. By considering simulations of near field effluent plume behaviour in relation to long term ambient nutrient patterns specific periods of the year and depth intervals have been identified when outfalls would have an increased opportunity to influence bloom development, especially the upper half of the water column during late summer. However, algal blooms appear to be principally driven by seasonal oceanic nutrient enrichment. The research presented in this thesis, together with companion research previously published by the author and routine ongoing monitoring, indicate the viability of disposal of the Sydney’s excess sewage effluent (after source control and re-use options have been exhausted) via existing deepwater outfalls.
In contrast, inner CBL settings with coastal irregularities (e.g. headlands and bays) have a greater propensity to trap pollutants. A new hydrodynamically relevant morphological classification of New South Wales bays, headlands and islands provides both broad context for case studies and guides preliminary assessments for other locations. This classification reveals a borderline propensity for flow separation and re-circulation in the lee of Corambirra Point which is the focus of the second case study off Coffs Harbour in northern NSW. Direct observations and 3D finite difference hydrodynamic (Eulerian) and particle tracking (Lagrangian) model simulations quantify transient re-circulation associated with local current accelerations and a persistent shear zone located in the wake to the south of Corambirra Point. The flux of ambient water across the prescribed outfall alignment increases eighteen fold, over a shear zone spanning a cross-shore distance of just 1.4km (from 1.6km to 3km offshore). In contrast, the potential for re-entrainment and trapping of effluent in transient re-circulation cells was demonstrated to be insignificant. The proposed location of the outfalls was 1.5km offshore whereas the greatest gain per unit extension of the proposed discharge point coincides with the centre of the shear zone located ~2km offshore.
These case studies illustrate specific coastal boundary layer effects and indicate how an understanding of the spatial and temporal scales of these effects can be used to target more specific assessments of potential pollutant impacts. Simple morphological risk assessment tools are also presented to identify factors and processes which limit the exposure of sensitive environments to high pollutant concentrations and loads. Eddy retention effects are generally not incorporated in existing near field models but potential re-entrainment effects in wake zones can be assessed through the eddy retention value, which is introduced in this thesis. Although the approach presented here is focused on New South Wales coastal waters, the framework serves as a basis for general application elsewhere, and as a foundation for further refinement for application to NSW coastal waters.
Existing scientific literature indicates that coastal boundary layer processes also shape the distributions of the biological species and communities. This further motivates the development of a process based understanding of coastal boundary layer dynamics as a fundamental platform to support environmental protection and biodiversity conservation initiatives
Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: Results from a pilot service implemented during the first pandemic wave.
No full textDuring the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves
U.S. IOOS coastal and ocean modeling testbed : inter-model evaluation of tides, waves, and hurricane surge in the Gulf of Mexico
No full text© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 5129–5172, doi:10.1002/jgrc.20376.A Gulf of Mexico performance evaluation and comparison of coastal circulation and wave models was executed through harmonic analyses of tidal simulations, hindcasts of Hurricane Ike (2008) and Rita (2005), and a benchmarking study. Three unstructured coastal circulation models (ADCIRC, FVCOM, and SELFE) validated with similar skill on a new common Gulf scale mesh (ULLR) with identical frictional parameterization and forcing for the tidal validation and hurricane hindcasts. Coupled circulation and wave models, SWAN+ADCIRC and WWMII+SELFE, along with FVCOM loosely coupled with SWAN, also validated with similar skill. NOAA's official operational forecast storm surge model (SLOSH) was implemented on local and Gulf scale meshes with the same wind stress and pressure forcing used by the unstructured models for hindcasts of Ike and Rita. SLOSH's local meshes failed to capture regional processes such as Ike's forerunner and the results from the Gulf scale mesh further suggest shortcomings may be due to a combination of poor mesh resolution, missing internal physics such as tides and nonlinear advection, and SLOSH's internal frictional parameterization. In addition, these models were benchmarked to assess and compare execution speed and scalability for a prototypical operational simulation. It was apparent that a higher number of computational cores are needed for the unstructured models to meet similar operational implementation requirements to SLOSH, and that some of them could benefit from improved parallelization and faster execution speed.This project was supported by NOAA
via the U.S. IOOS Office (award: NA10NOS0120063 and
NA11NOS0120141
Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings
No full textThere is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays-a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)-on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections
Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 infection early in the pandemic and the role of unidentified cases in transmission
No full textOBJECTIVES: Analysis of nosocomial transmission in the early stages of the pandemic at a large multi-site healthcare institution. Nosocomial incidence is linked with infection control interventions. METHODS: Viral genome sequence and epidemiological data were analysed for 574 consecutive SARS-CoV-2 PCR-positive patients including 86 nosocomial cases during the first 19 days of the pandemic. RESULTS: 44 putative transmission clusters were found through epidemiological analysis, which included 234 cases and all 86 nosocomial cases. SARS-CoV-2 genome sequence was obtained from 168/234 (72%) of these cases in epidemiological clusters, including 77/86 (90%) nosocomial cases. Only 75/168 (45%) linked, sequenced cases were not refuted by applying genomic data, creating 14 final clusters accounting for 59/77 (77%) sequenced nosocomial cases. Viral haplotypes from these clusters were enriched 1-14x (median 4x) compared to the community. Three factors implicated unidentified cases in transmission: i) community-onset or indeterminate cases were absent in 7/14 (50%) of clusters ii) 4 (29%) clusters had additional evidence of cryptic transmission. iii) In 3 (21%) clusters, diagnosis of the earliest case was delayed which may have facilitated transmission. Nosocomial cases decreased to low levels (0-2 per day) despite continuing high numbers of admissions of community-onset SARS-CoV-2 cases (40-50 per day) and before the impact of introducing universal face-masks or banning hospital visitors. CONCLUSION: Genomics was necessary to accurately resolve transmission clusters Our data supports unidentified cases, such as healthcare workers or asymptomatic patients, as important vectors of transmission. Evidence is needed to ascertain whether routine screening increases case ascertainment and limits nosocomial transmission
Real-world evaluation of a novel technology for quantitative simultaneous antibody detection against multiple SARS-CoV-2 antigens in a cohort of patients presenting with COVID-19 syndrome
No full textThis is the final version. Available from the publisher via the DOI in this record.An evaluation of a rapid portable gold-nanotechnology measuring SARS-CoV-2 IgM, IgA and IgG antibody concentrations against spike 1 (S1), spike 2 (S) and nucleocapsid (N) was conducted using serum
samples from 74 patients tested for SARS-CoV-2 RNA on admission to hospital, and 47 historical control
patients from March 2019. 59 patients were RNA(+) and 15 were RNA(−). A serum (±) classification was
derived for all three antigens and a quantitative serological profile was obtained. Serum(+) was identified
in 30% (95% CI 11–48) of initially RNA(−) patients, in 36% (95% CI 17–54) of RNA(+) patients before 10
days, 77% (95% CI 67–87) between 10 and 20 days and 95% (95% CI 86–100) after 21 days. The patientlevel diagnostic accuracy relative to RNA(±) after 10 days displayed 88% sensitivity (95% CI 75–95) and
75% specificity (95% CI 22–99), although specificity compared with historical controls was 100% (95%CI
91–100). This study provides robust support for further evaluation and validation of this novel technology
in a clinical setting and highlights challenges inherent in assessment of serological tests for an emerging
disease such as COVID-19.Engineering and Physical Sciences Research Council (EPSRC)Attomarker Lt
Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma
No full textThe immune system employs several checkpoint pathways to regulate responses, maintain homeostasis and prevent self-reactivity and autoimmunity. Tumor cells can hijack these protective mechanisms to enable immune escape, cancer survival and proliferation. Blocking antibodies, designed to interfere with checkpoint molecules CTLA-4 and PD-1/PD-L1 and counteract these immune suppressive mechanisms, have shown significant success in promoting immune responses against cancer and can result in tumor regression in many patients. While inhibitors to CTLA-4 and the PD-1/PD-L1 axis are well-established for the clinical management of melanoma, many patients do not respond or develop resistance to these interventions. Concerted efforts have focused on combinations of approved therapies aiming to further augment positive outcomes and survival. While CTLA-4 and PD-1 are the most-extensively researched targets, results from pre-clinical studies and clinical trials indicate that novel agents, specific for checkpoints such as A2AR, LAG-3, IDO and others, may further contribute to the improvement of patient outcomes, most likely in combinations with anti-CTLA-4 or anti-PD-1 blockade. This review discusses the rationale for, and results to date of, the development of inhibitory immune checkpoint blockade combination therapies in melanoma. The clinical potential of new pipeline therapeutics, and possible future therapy design and directions that hold promise to significantly improve clinical prognosis compared with monotherapy, are discussed
Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans
No full textAntibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection
Resilient SARS-CoV-2 diagnostics workflows including viral heat inactivation
No full textThere is a worldwide need for reagents to perform SARS-CoV-2 detection. Some laboratories have implemented kit-free protocols, but many others do not have the capacity to develop these and/or perform manual processing. We provide multiple workflows for SARS-CoV-2 nucleic acid detection in clinical samples by comparing several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), RNAdvance Blood/Viral (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek). We also compared One-step RT-qPCR reagents: TaqMan Fast Virus 1-Step Master Mix (FastVirus, ThermoFisher Scientific), qPCRBIO Probe 1-Step Go Lo-ROX (PCR Biosystems) and Luna® Universal Probe One-Step RT-qPCR Kit (Luna, NEB). We used primer-probes that detect viral N (EUA CDC) and RdRP. RNA extraction methods provided similar results, with Beckman performing better with our primer-probe combinations. Luna proved most sensitive although overall the three reagents did not show significant differences. N detection was more reliable than that of RdRP, particularly in samples with low viral titres. Importantly, we demonstrated that heat treatment of nasopharyngeal swabs at 70°C for 10 or 30 min, or 90°C for 10 or 30 min (both original variant and B 1.1.7) inactivated SARS-CoV-2 employing plaque assays, and had minimal impact on the sensitivity of the qPCR in clinical samples. These findings make SARS-CoV-2 testing portable in settings that do not have CL-3 facilities. In summary, we provide several testing pipelines that can be easily implemented in other laboratories and have made all our protocols and SOPs freely available at https://osf.io/uebvj/
