Blast Wave Clearing Effects on Finite-Sized Targets Subjected to Explosive Loads

A high explosive detonation is characterised by the rapid release of energy as a mass of explosive material is converted into a high pressure, high temperature gas. As this gas expands it displaces the surrounding air, causing a high pressure shock wave to travel through the air away from the explosive at supersonic speed. This shock wave can potentially cause significant damage as it impacts a structure -- it is the challenge of the engineer to ensure that our infrastructure is robust enough to be able to withstand such extreme loading. The first aspect of blast engineering is to be able to predict and quantify the spatial and temporal variation of the load acting on the target to a sufficient level of accuracy. Whilst experimental trials and higher order numerical schemes offer useful insights, the time and expense associated with such methods renders them unusable for the early stages of design. Accordingly, semi-empirical blast predictions are more often favoured. These semi-empirical predictions assume that the target forms a reflecting surface that is effectively infinite in dimensions perpendicular to the direction of travel of the blast wave. For finite-sized targets, however, the presence of target edges is known to significantly alter the pressure acting on the loaded face in a process known as blast wave clearing -- diffraction of the blast wave around the target which causes a relief wave to sweep in from the edges of the reflecting surface. Current methods for predicting blast wave clearing fail to capture the physical process, and as such are inadequate at providing valid blast pressure predictions. Approximating the relief wave as an acoustic pulse allows for accurate predictions which are based on physically valid principles. Accurate prediction of cleared blast pressure loads has enabled the effect of blast wave clearing to be identified and quantified. Secondly, the target response to this load must be predicted. The single-degree-of-freedom (SDOF) method approximates the distributed properties of the real life system into single point equivalent values. This procedure is well established for the target properties, and by transforming the spatial variation of cleared blast pressure in a similar manner (by conserving energy between real life and equivalent systems), clearing blast pressure loads can be modelled in SDOF analyses. The marked effect of clearing on structural response has been clearly demonstrated in this thesis. The combined improvements to both load prediction and response modelling has allowed a full parametric study to be conducted on finite-sized targets subjected to blast loads. Neglecting clearing can be largely over-conservative for small targets, and for targets with plastic resistance significantly less than the applied transient blast force. It has been observed, however, that neglecting clearing can sometimes be non-conservative through a combination of target rebound, plasticity and early negative pressures caused by the clearing waves. Findings in the PhD thesis should be used to highlight the complex nature of blast-target interaction, particularly when blast wave clearing is concerned, and should dispel the myth that a design will be safe if clearing is neglected. Results presented in the study can also be used by practising engineers to determine the likely effect that blast wave clearing will have on any configuration of explosive mass, stand-off, target size and dynamic properties, and the numerical models developed within have the potential for widespread use in existing commercial software

Strong Lens Models for 37 Clusters of Galaxies from the SDSS Giant Arcs Survey

We present strong gravitational lensing models for 37 galaxy clusters from the SDSS Giant Arcs Survey. We combine data from multi-band Hubble Space Telescope WFC3imaging, with ground-based imaging and spectroscopy from Magellan, Gemini, APO, and MMT, in order to detect and spectroscopically confirm new multiply-lensed background sources behind the clusters. We report spectroscopic or photometric redshifts of sources in these fields, including cluster galaxies and background sources. Based on all available lensing evidence, we construct and present strong lensing mass models for these galaxy clusters.Comment: 53 pages; submitted to ApJ

Investigations into the photophysical and electronic properties of pnictoles and Their pnictenium counterparts

The reaction of phosphole/arsole starting materials with a series of halide abstraction reagents afforded their respective phosphenium/arsenium complexes. UV–vis absorption and luminescence studies on these cations showed interesting emission profiles, which were found to be dependent upon counterion choice. The addition of a reductant to the phosphole reagent garnered a dimeric species with a central P–P bond, which when heated was found to undergo homolytic bond cleavage to produce an 11π radical complex. Electron paramagnetic resonance (EPR), supported by density functional theory (DFT) calculations, was used to characterize this radical species

Lens Model and Source Reconstruction Reveal the Morphology and Star Formation Distribution in the Cool Spiral LIRG SGAS J143845.1++145407

We present $Hubble\ Space\ Telescope$ ($HST$) imaging and grism spectroscopy of a strongly lensed LIRG at $z=0.816$, SGAS 143845.1$+$145407, and use the magnification boost of gravitational lensing to study the distribution of star formation throughout this galaxy. Based on the $HST$ imaging data, we create a lens model for this system; we compute the mass distribution and magnification map of the $z=0.237$ foreground lens. We find that the magnification of the lensed galaxy ranges between $2$ and $10$, with a total magnification (measured over all the images of the source) of $\mu=11.8^{+4.6}_{-2.4}$. We find that the total projected mass density within $\sim34$ kpc of the brightest cluster galaxy is $6.0^{+0.3}_{-0.7}\times10^{12}\,M_{\odot}$. Using the lens model we create a source reconstruction for SGAS 143845.1$+$145407, which paired with a faint detection of H$\alpha$ in the grism spectroscopy, allows us to finally comment directly on the distribution of star formation in a $z\sim1$ LIRG. We find widespread star formation across this galaxy, in agreement with the current understanding of these objects. However, we note a deficit of H$\alpha$ emission in the nucleus of SGAS 143845.1$+$145407, likely due to dust extinction.Comment: 7 pages, 8 figures, 2 table

Horses for courses? Assessing the potential value of a surrogate, point-of-care test for SARS-CoV-2 epidemic control.

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV-2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV-2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV-2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2-specific POCTs-when they become available-are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide

Antibody response to SARS-CoV-2 infection in humans: A systematic review.

BACKGROUND: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. METHODS: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. CONCLUSIONS: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised

T cell response to SARS-CoV-2 infection in humans: A systematic review.

BACKGROUND: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised

Expanding eligibility and improving quality of cervical cancer screening in Estonia: The 2021 reforms.

Estonia has one of the highest death rates from cervical cancer in the European Union despite having had a population-based screening programme for over 15 years. In 2021, this high disease burden, alongside a new national cancer prevention plan, prompted a series of cervical cancer screening programme reforms to address low screening uptake and evidence of variable screening test quality. The reforms had three main elements: expansion of eligibility to all women aged 30-65 regardless of insurance status; increasing test provision by enabling family physicians to take screening samples and introducing self-sampling; and improving testing procedures, replacing cytology with HPV testing as the primary screening test. Although the impact of these changes is yet to be seen, early signs suggest increased programme participation. However, at 51 %, further action to address barriers to uptake will likely be necessary. If Estonia is to avoid another period of policy dormancy, as happened between 2006 and 2021, greater clarity on screening programme accountability is required. The establishment of the National Cancer Screening Group may enable this. The first test will be the delivery of an end-to-end evaluation of the reformed programme, with an emphasis on equity of access. The next step will be to develop and deliver solutions that respond to these needs

Availability, scope and quality of monkeypox clinical management guidelines globally : a systematic review

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z) and the Bill & Melinda Gates Foundation (OPP1209135). The GloPID-R Secretariat is a project that receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874667. SL is an MRC Clinical Research Training fellow (MR/T001151/1).Background Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. Methods For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Results Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1–7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. Conclusion Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A ‘living guideline’ framework is recommended. PROSPERO registration number CRD42020167361.Publisher PDFPeer reviewe

Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines

Background: The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. Methods: Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively. Results: Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1–7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively. Conclusions: Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A ‘living guideline’ framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries