35 research outputs found
Advancing NZ hospital seismic readiness: creating a post-earthquake functionality dashboard
Continued functionality of critical infrastructure systems, such as hospitals, shortly after an earthquake is expected. However, experience indicates that there may be some disruption due to damage, outages, or access that vary in size and duration. While damage to structural components can have significant life safety and economic implications, damage to non-structural components or failures of the interconnected and interdependent supporting infrastructure systems can also have a substantial impact on the operability. A functionality dashboard to rapidly identify drops in functional performance is needed. The dashboard must be based on real and possible disruptions, including data from previous disruptive events. The dashboard utilises a functionality database and risk analysis tools to holistically predict a level of post-disaster functionality. Creating a functionality database from past earthquake events provides the necessary information to create a representative event tree of hospital performance. Drops in functionality are governed by fault trees that are created based on the data gathered in the functionality database. These tools provide the engine for a hospital functionality dashboard for estimating hospital functionality to scenario events. Use of the dashboard will help determine critical links between hospital components impacting functionality and provide needed information for improving facility design. It will also be useful for testing the implementation of emergency procedures linking the physical environment with human and organisation requirements
Quantifying functionality of buildings to natural hazards
Continued functionality of critical infrastructure systems shortly after an earthquake is expected. However, experience has shown that this is often not the case. Building with limited or no structural damage may still experience significant non-structural damage or be impacted by surrounding and interconnected infrastructural failures that can a sustained and substantial impact on the operability of the building. A method to rapidly identify how damage, outages, or blockages are linked to drops in functional performance measures for the people and organisations is being developed for hospitals and will be further expanded to other building occupancies and infrastructure including commercial buildings, critical facilities, and housing. Immediate understanding of damage and the subsequent effects of the damage can provide instant feedback on the level of operational functionality. This poster show how this is currently being implemented for hospitals and how this work can be extended to other buildings. Functionality is determined through the use of risk analysis tools that help to quantitatively define probabilities of building and organisational functionality. The project aims to take a holistic view of a building’s performance, considering the physical and spatial factors of damage, use and needs of the structure, and interconnected interdependencies
Metarhizium anisopliae Pathogenesis of Mosquito Larvae: A Verdict of Accidental Death
Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Background
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
Methods
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and
ClinicalTrials.gov
,
NCT00541047
.
Findings
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Interpretation
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Funding
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society
Using tertiary building performance to define post-disaster functionality timeframes for community recovery and resilience
Building damage from earthquakes can have significant consequences for communities, leading to direct and indirect losses. These losses include casualties and repair costs, reduced productivity and well-being. Current building codes prioritize life safety by aiming to prevent deaths, but lack provisions for repairability and functionality, resulting in potentially long recovery times. There has been growing interest in enhancing post-earthquake building functionality, which refers to a building's ability to serve its intended purpose. Beyond life safety, additional functionality states have been defined, including re-occupancy (safe shelter), functional recovery (basic service provision), and full functionality (restoration to pre-earthquake conditions). Several frameworks and design methodologies have been developed in the United States to understand the requirements for achieving these higher functionality states. However, these frameworks predominantly focus on structural and non-structural component damage, with limited consideration for external impacts (e.g., neighbouring buildings) and social factors (e.g., pre-event planning and occupancy policies). Furthermore, their applicability outside the United States and on a broader scale remains uncertain. In response to the disruptions caused by the Canterbury earthquake sequence in 2010/2011, New Zealand government organizations have expressed a desire to move beyond existing life safety codes and increase the country's resilience. The requirements for achieving higher functionality states within a New Zealand context remains an active research area. This poster proposes developing a framework for post-earthquake building functionality tailored explicitly to New Zealand. Tertiary education institutions in New Zealand are selected as a case study due to their functional similarities to other community buildings such as libraries, offices, cafes, and auditoriums. The research objectives include learning from institutions affected by the Canterbury earthquake sequence, understanding the needs of institutions nationwide, and investigating the framework's applicability to other types of buildings. The poster presents these objectives and details
on required resources, timelines, risks, and ethical considerations
Unimolecular Dissociation of 1‑Methylpyrene Cations: Why Are 1‑Methylenepyrene Cations Formed and Not a Tropylium-Containing Ion?
1-Methylpyrene radical
cations undergo the loss of a hydrogen atom
at internal energies above the first dissociation threshold. Imaging
photoelectron photoion coincidence spectroscopy was employed in combination
with RRKM modeling to determine a 0 K activation energy of 2.78 ±
0.25 eV and an entropy of activation of 6 ± 19 J K<sup>–1</sup> mol<sup>–1</sup> for this H-loss reaction. The ionization
energy of 1-methylpyrene was measured by mass-selected threshold photoelectron
spectroscopy to be 7.27 ± 0.01 eV. These values were found to
be consistent with calculations at the CCSD/6-31G(d)//B3-LYP/6-31G(d)
level of theory showing that the formation of the 1-methylenepyrene
cation (resulting from H loss from the methyl group) is kinetically
more favorable than the formation of a tropylium-containing product
ion that is structurally analogous to the formation of the tropylium
cation in H loss from ionized toluene. The shift away from a tropylium-containing
structure was found to be due to the increased ring strain imposed
on the C7 moiety when it is bound to three fused benzene rings. The
RRKM results allow for the derivation of the Δ<sub>f</sub><i>H</i><sub>0</sub><sup>o</sup> (1-methylenepyrene cation) of
945 ± 31 kJ mol<sup>–1</sup>
Unimolecular Dissociation of 1‑Methylpyrene Cations: Why Are 1‑Methylenepyrene Cations Formed and Not a Tropylium-Containing Ion?
1-Methylpyrene radical
cations undergo the loss of a hydrogen atom
at internal energies above the first dissociation threshold. Imaging
photoelectron photoion coincidence spectroscopy was employed in combination
with RRKM modeling to determine a 0 K activation energy of 2.78 ±
0.25 eV and an entropy of activation of 6 ± 19 J K<sup>–1</sup> mol<sup>–1</sup> for this H-loss reaction. The ionization
energy of 1-methylpyrene was measured by mass-selected threshold photoelectron
spectroscopy to be 7.27 ± 0.01 eV. These values were found to
be consistent with calculations at the CCSD/6-31G(d)//B3-LYP/6-31G(d)
level of theory showing that the formation of the 1-methylenepyrene
cation (resulting from H loss from the methyl group) is kinetically
more favorable than the formation of a tropylium-containing product
ion that is structurally analogous to the formation of the tropylium
cation in H loss from ionized toluene. The shift away from a tropylium-containing
structure was found to be due to the increased ring strain imposed
on the C7 moiety when it is bound to three fused benzene rings. The
RRKM results allow for the derivation of the Δ<sub>f</sub><i>H</i><sub>0</sub><sup>o</sup> (1-methylenepyrene cation) of
945 ± 31 kJ mol<sup>–1</sup>
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