143174 research outputs found
Sort by
Visual analysis of firebrand generation from a large mass timber compartment fire
No full textFirebrands, the solid burning fragments transported by fire and wind, are a key mechanism of wildfire spread.
Firebrands are also generated by building fires, but are not typically considered in building fire protection,
and can be a more prevalent hazard in mass timber buildings. This paper presents the first study of firebrands
generated from a large mass timber compartment fire (CodeRed #01) and ejected from openings. Firebrand
location and velocity was studied using particle Streak Velocimetry. Commercial cameras were used as a simple
and field-deployable alternative to more complex approaches, whilst also providing a method of approximating
the gas flow-field. Over 15600 firebrands were ejected from one opening over 17 min, reaching up to 300
firebrands in one instance. Maximum firebrand velocities of 14 −1 and mean velocities between 2 − 6 −1
were observed. Firebrands had greater velocities along the external venting flame centreline, while the peak
of firebrand number densities were at the outer region of the external venting flame. Computer vision was
trained and validated to rapidly and automatically detect firebrands whilst minimising false negatives and false
positives. This paper finds that firebrands can be generated in significant quantities from mass timber building
fires, posing a significant hazard to nearby structure
Toward setting minimum and optimal data to report for malaria molecular surveillance with targeted sequencing: the “what” and “why”
No full textThe coronavirus disease 2019 pandemic showcased the power of genomic surveillance in tracking infectious diseases, driving rapid public health responses, and global collaboration. This same infrastructure is being leveraged for malaria molecular surveillance (MMS) in Africa to address challenges such as artemisinin partial resistance and deletions in the Plasmodium falciparum histidine-rich protein 2 and 3 genes. However, variability in reporting sequencing methods and data reporting currently limits the validation, comparability, and reuse of data. To maximize the impact of MMS, minimal and optimal data that are key for validation and maximizing transparency and findable, accessible, interoperable, and reusable principles are proposed for reporting. Rather than focusing on specific data formats, in the current study, the authors propose what should be reported and why. Progressing to reporting individual infection-level polymorphism or microhaplotype data is central to maximizing the impact of MMS. Reporting must adhere to local regulatory practices and ensure proper data oversight and management, preventing data colonialism and preserving opportunities for data generators. With malaria’s challenges transcending borders, reporting and adopting standardized practices are essential to advancing research and strengthening global public health efforts
S-098 Pregnancy outcomes in women with heart disease diagnosed in pregnancy vs. pre-pregnancy: data from ROPAC Registry
No full textLinking microscopy to diffusion MRI with degenerate biophysical models: an application of the Bayesian EstimatioN of CHange (BENCH) framework
No full textBiophysical modelling of diffusion MRI (dMRI) is used to non-invasively estimate microstructural features of tissue, particularly in the brain. However, meaningful description of tissue requires many unknown parameters, resulting in a model that is often ill-posed. The Bayesian EstimatioN of CHange (BENCH) framework was specifically designed to circumvent parameter fitting for ill-conditioned models when one is simply interested in interpreting signal changes related to some variable of interest. To understand the biological underpinning of some observed change in MR signal between different conditions, BENCH predicts which model parameter, or combination of parameters, best explains the observed change, without having to invert the model. BENCH has been previously used to identify which biophysical parameters could explain group-wise dMRI signal differences (e.g., patients vs. controls); here, we adapt BENCH to interpret dMRI signal changes related to continuous variables. We investigate how parameters from the dMRI standard model of white matter, with an additional sphere compartment to represent glial cell bodies, relate to tissue microstructure quantified from histology. We validate BENCH using synthetic dMRI data from numerical simulations. We then apply it to ex-vivo macaque brain data with dMRI and microscopy metrics of glial density, axonal density, and axonal dispersion in the same brain. We found that (i) increases in myelin density are primarily associated with an increased intra-axonal volume fraction and (ii) changes in the orientation dispersion derived from myelin microscopy are linked to variations in the orientation dispersion index. Finally, we found that the dMRI signal is sensitive to changes in glial cell load in the brain white matter, though no single parameter in the extended standard model was able to explain this observed signal change
Optimising the design and delivery of ground-source energy systems through interdisciplinary research
No full textSaFEGround – Sustainable, Flexible and Efficient Ground source energy systems – is an interdisciplinary research project focused on ground source energy systems (GSESs) and their potential contribution to the decarbonisation of heating and cooling. It covers several interlinked domains, spanning a range of scales. This paper summarises the key outcomes of the project and how they deliver new insights into the design and optimisation of GSESs. It is found that at the whole-energy system level, distributed domestic GSESs require substantial subsidies to be competitive with gas boilers and air-source heat pumps (ASHPs), and that gas boilers are preferred at low gas prices while GSESs require high proportional subsidies. Higher electricity grid upgrade costs favour GSESs. The true value of GSESs likely lies in (large) new-built properties as well as centralised heating systems, such as communal and district heating schemes
Population pharmacokinetics of rifampicin in plasma and cerebrospinal fluid in adults with tuberculosis meningitis
No full textAbstract
Background
Several ongoing clinical trials are evaluating high-dose rifampicin (up to 35 mg/kg) for tuberculous meningitis (TBM). However, rifampicin pharmacokinetics at higher doses is not fully characterized, particularly in cerebrospinal fluid (CSF), the site of TBM disease.
Methods
In a randomized controlled trial, adults with HIV-associated TBM were assigned to experimental arms of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, or a control arm that received the standard of care with 10 mg/kg of oral rifampicin. Rifampicin concentrations, including the unbound fraction, were measured on plasma samples, and CSF was collected on days 3 and 28 of study enrollment. Data were analyzed by nonlinear mixed effects modeling.
Results
In total, 400 plasma and 44 CSF rifampicin concentrations from 48 participants were used for model development. The median (range) age and weight were 39 years (25–78) and 60 kg (30–107). Rifampicin pharmacokinetics was best described by a 2-compartment disposition model with first-order transit oral absorption and elimination via saturable hepatic extraction. Typical clearance values for the standard dose for days 3 and 28 were 33.1 and 41.4 L/h, respectively; high-dose values were 46.1 and 70.2 L/h. The CSF-plasma ratio was approximately 6% and the equilibration half-life was 3.2 hours. Simulated standard-dose rifampicin did not reach CSF concentrations above the critical concentration for Mycobacterium tuberculosis.
Conclusions
CSF penetration with standard-dose rifampicin is low. Our findings support continued evaluation of high-dose rifampicin for TBM treatment
From titer to quality: exploring reinforcement learning for bioprocess control in silico
No full textThe production of monoclonal antibodies in mammalian cells is a highly
complex and nonlinear process. The industry standard for controlling this
process fails to capture its complex dynamics, leading to batch-to-batch vari ability. This inherent complexity makes bioprocesses challenging to model
purely mechanistically, while the lack of rich experimental datasets and the
need for interpretability in control policies further prevent the use of fully
data-driven solutions. We propose a hybrid methodology for optimising the
nutrient feeding strategy that leverages Reinforcement Learning (RL) with
mechanistic models of cellular metabolism and glycosylation. The RL agent
is trained using an off-policy method for data efficiency and is capable of
learning from partial observations of the state, which allows for improved
generalization. The controller is adaptable to processes with or without addi tional product quality considerations, such as glycosylation. We demonstrate
that accounting for product glycosylation yields different control strategies
whereas neglecting it to focus on titer alone can compromise product quality.
The continuous learning abilities of the proposed method ensure adaptability
in response to process changes, while the inclusion of a mechanistic model in
the environment aids in the interpretability of the learned control actions
Grain growth inhibition in tungsten diboride radiation shielding via boron particle reinforcement
No full textTungsten diboride is a candidate neutron shielding material for compact fusion reactors. The material’s tolerance for radiation induced swelling may be improved by refining the grain size. In this work, we have stabilised fine grain structures by reinforcing the WB2 matrix with a minor volume fraction of free boron particles. The particles restricted the average grain size to 1–2 μm below 2100 °C. Above this, the boundaries decoupled from the particles and the grain size became bimodal, with abnormally large and highly elongated grains (30–80 μm in diameter). The grain growth degraded hardness and indentation toughness, e.g. from 40 to 30 GPa at 0.1 kg load, and from 7.5 to 5.2 MPa m1/2 respectively. By contrast, it increased room temperature thermal conductivity from 36 to 51 W m−1 K−1 due to decreased phonon-boundary scattering. The study provides a design pathway for stabilising fine-grained materials that may have improved radiation damage tolerance
A new screening framework to support the identification of exogenous particles and suspect microplastics in situ in pathological tissue samples
No full textBackground
Microplastics are ubiquitous environmental pollutants that have been detected in various human tissues. Often the particle sizes reported challenge established theory in toxicokinetics, and fundamental data on whether exogenous microparticles can enter tissues (and which tissues) is needed. This observational and method validation study aimed to develop a screening framework to determine whether particles including microplastics can access tissues using human ileal tissue sections and to investigate the presence of exogenous particles within the subepithelial mucosa.
Methods
As proof of concept that exogenous particles may translocate into tissues, a screening framework was established using polarised light microscopy (PLM), to identify birefringent particles in ileal tissue sections from 101 subjects. The population included adults who had undergone endoscopy and biopsy for the investigation of bowel symptoms at King’s College Hospital. Exclusion criteria were applied to differentiate between true particles and procedural contaminants. The remaining particles were analysed for their morphology and size. To further illustrate the potential for plastic to access intestinal tissue, a bulk intestinal tissue sample underwent a basic digestion, filtration, and analysis using pyrolysis gas chromatography mass spectrometry.
Findings
Results revealed the presence of subepithelial birefringent particles in a small number of ileal tissue sections. However, of the 35 samples containing sub-epithelial particles, 31 (i.e., 91% of observations) were concluded to be due to procedural contamination. Of the ‘true’ observations, some of these particles, which include starch, likely entered the tissue via persorption. Additionally, a single viscose fibre was observed within the lumen of the small intestine. Supplemental chemical
data finding signatures of polypropylene and polyvinylchloride demonstrate how the framework would fit in a wider analytical pipeline.
Interpretation
This study highlights the importance of a robust screening framework for the identification of particles and suspect microplastics in human tissues. While the frequency of particles like microplastics in the subepithelial mucosa was low, the findings suggest that microplastics could indeed penetrate the intestinal epithelium and this was supplemented with example chemical data.
Further research is needed to investigate the distribution, accumulation, and potential health effects of microplastics in human tissues.
Funding
Medical Research Counci
Assessing cardiac function in obstructive sleep apnea using a novel metric: integrating the respiratory event frequency and desaturation duration
No full textObjectives
Obstructive sleep apnea (OSA) is associated with impaired cardiac function, evidenced by a decreased left ventricular ejection fraction (LVEF). Traditional measures, including the apnea-hypopnea index (AHI) and lung-to-finger circulation time (LFCT), do not simultaneously consider the hypoxemic duration, frequency, and severity. This study introduces the respiratory event response time area (RERTA), integrating duration- and frequency-based OSA indices, and examined its associations with the LVEF.
Methods
We retrospectively analyzed data from individuals who underwent polysomnography (PSG) and echocardiography within the previous 6 months. LFCT was calculated as the mean time from desaturation onset after a respiratory event to the lowest recorded oxygen saturation (SpO2). The RERTA, a joint metric that reflects the event frequency and desaturation duration, was determined as the square root of the product of the AHI and mean LFCT. PSG parameters and related metrics were then examined for associations with echocardiographic measures.
Results
Among 34 participants (10 with mild-to-moderate and 24 with severe OSA), the severe group exhibited a lower median LVEF than the mild-to-moderate group (64.00% [61.00%–68.50%] vs. 70.00% [66.50%–72.75%], p < 0.05). After adjusting for age, gender, and the body-mass index (BMI), each 1-event/h increase in the AHI was linked to a borderline reduction in the LVEF (-0.71%, 95% CI: -1.42 to 0.00; p = 0.05). A 1-unit increase in the RERTA corresponded to a 0.33% decrease in the LVEF (95% CI: -0.62% to -0.04%, p < 0.05).
Conclusions
The RERTA combines the AHI and mean LFCT, providing a joint assessment of circulatory stress in patients with OSA. This study highlights its potential utility in evaluating cardiac function associated with OSA, which can serve as a basis for future prospective research