Biology subjects

Webster, G.

Publications and source records attributed to Webster, G..

8 recordsLinked to original sources

bioRxiv2026

Cumulative Transfer Function for Assessment of MRI-Induced RF Heating Risk in Pediatric Patients Implanted with Bifurcated Leads

PurposeRF-induced heating remains a major barrier to MRI access for patients with epicardial cardiac implantable electronic devices (CIEDs). Although ISO/TS 10974 Tier-3 transfer function (TF) methods are established for unbranched leads, no analogous framework exists for bifurcated leads, in which branch asymmetry and inter-branch coupling may substantially alter heating. We developed and validated a cumulative transfer function (cTF) framework to address this gap. MethodsFollowing ISO/TS 10974 Tier-3 formalism, we measured, calibrated, and validated cTFs for a commercial 35 cm bipolar epicardial lead at 1.5 T. The framework explicitly accounts for branch-specific response and cross-branch coupling. Validation was performed with 24 canonical lead configurations in a homogeneous phantom and, without recalibration, in a heterogeneous anthropomorphic pediatric phantom with clinically derived trajectories. A single-branch TF approximation served as a comparator. The validated cTF was applied to predict RF heating across adult and pediatric human models at multiple imaging landmarks. ResultsCompared with the single-branch TF approximation, the cTF reduced prediction error by nearly 70% in the primary validation dataset. In secondary validation, the cTF maintained low error across clinically relevant trajectories and imaging landmarks. In human models, the framework revealed marked anatomy- and landmark-dependent variation in predicted heating for the tested 35 cm lead, with low predicted heating in pediatric models and substantially higher heating in selected adult chest and upper abdominal imaging scenarios. ConclusionThe cTF provides a validated framework for RF-heating assessment of bifurcated leads and substantially improves prediction accuracy over single-branch TF approximations that neglect branch coupling.

bioengineering↗

bioRxiv2026

RF Heating of Bipolar Epicardial Implants during MRI at 0.55 T and 1.5T: Effect of Device Length and Termination Conditions

Pediatric patients with epicardial cardiac implantable electronic devices (CIEDs) are frequently excluded from the Magnetic Resonance Imaging (MRI) primarily due to RF heating safety concerns. In this study we evaluate RF heating of two bipolar epicardial leads during MRI at 0.55 T and 1.5 T under different termination conditions. Our findings showed that the mean RF heating was significantly reduced at 0.55 T MRI compared to that at 1.5 T. Similarly, the RF heating at 0.55 T MRI was highest for full system whereas, during MRI at 1.5 T, the RF heating was highest for the capped abandoned lead, showing dependence of RF heating pattern on MRI field strength. While RF heating at both fields surpassed the safety limit, the capped abandoned leads at 1.5 T MRI showed significantly higher RF heating with temperature rise surpassing 50{degrees}C in some of the cases. These results highlight the difference in RF heating of bipolar epicardial leads compared to the previously reported findings for monopolar epicardial lead which showed smallest heating for capped abandoned lead at both field strengths. These findings emphasize the necessity of device-specific evaluations at each field-strength to inform clinical decision-making and expand MRI access for this vulnerable population.

biophysics↗

bioRxiv2025

Evaluating a structured expert elicitation approach for adaptive conservation: Lessons from five years in practice

Threatened species management relies on Ex ante estimates of species responses to different interventions to generate meaningful predictions. Structured expert elicitation is often used to generate these estimates, but comparisons of these expert-predicted outcomes with observed results are rare. This study aims to evaluate the utility of expert elicitation for adaptive management in the New South Wales Saving our Species (SoS) program in Australia by revisiting six species management plans that were generated from bespoke structured elicitation guidelines five years prior. Each species management plan included a defined scope, conceptual model, monitoring indicators and estimated response to management curves under different scenarios. Experts reviewed the conceptual models after five years of management and monitoring and compared the predicted response to management with observed monitoring data. In three of the six case studies, observed outcomes closely matched predictions. Where predictions diverged, factors such as unanticipated new threats and unexpected responses to interventions contributed to discrepancies. However, in all cases, the structured approach provided a clear logic for planning, enabling managers to systematically refine their understanding. The conceptual models and response curves proved valuable for collaboration, communication, and generating hypotheses for unexpected results. This work demonstrates the value of the bespoke guidelines in supporting adaptive management processes, strengthening the knowledge base for threatened species conservation while improving alignment between predictions and real-world outcomes.

ecology↗

bioRxiv2022

Age and lead configuration matter: A comparative study of RF-induced heating of epicardial and endocardial electronic devices in adult and pediatric anthropomorphic phantoms in 1.5 T MR

BackgroundChildren with congenital heart defects often have life-sustaining indications for a cardiac implantable electronic device (CIED). In children, these devices are typically sewn to the heart epicardium, but the FDA has never licensed an epicardial system as MR-Conditional due to limited data. Childrens hospitals default to either refusing MRI service to a vast majority of pediatric CIED patients or adopting a scan-all strategy based on results from adult studies. We argue that both approaches are flawed, and the risk-benefit decisions should be made on an individual basis. PurposeTo provide evidence-based knowledge on RF-induced heating of CIEDs in children and adults with epicardial and endocardial leads of different lengths. Study TypePhantom Field Strength/Sequence1.5 T. Assessment120 clinically relevant epicardial and endocardial device configurations were implemented in adult and pediatric anthropomorphic phantoms. Temperature rise was recorded during RF exposure at 1.5 T. Statistical TestsMeans comparisons were implemented using two-sample t-tests, reliability analysis using interclass correlation coefficient based on a single rating, absolute-agreement, 2-way mixed-effects model. ResultsThere was significantly higher RF heating of epicardial leads compared to endocardial leads in the pediatric phantom (3.4 {+/-} 3.0 vs. 0.6 {+/-} 0.4 {degrees}C, p<0.001); however, there was no significant difference in the adult phantom (3.0 {+/-} 3.2 vs. 2.0 {+/-} 1.8, p=0.16). Endocardial leads in the pediatric phantom generated significantly less RF heating than in the adult phantom (0.6 {+/-} 0.4 {degrees}C vs. 2.0 {+/-} 1.8 {degrees}C, p<0.001). Data ConclusionBody size and lead length significantly affected RF heating. For models based on younger children with short epicardial leads (e.g., 25cm), RF heating up to 12 {degrees}C was observed, delivering a cumulative thermal dose previously associated with tissue necrosis. In contrast, RF heating in model based on children with endocardial leads was well below the heating expected from physiologic fever (3 {degrees}C).

biophysics↗

bioRxiv2022

Modifying the trajectory of epicardial leads can substantially reduce MRI-induced RF heating in pediatric patients with a cardiac implantable electronic device

PurposeInfants and children with congenital heart defects, inherited arrhythmia syndromes, and congenital cardiac conduction disorders often receive epicardial implantable electronic devices. Unfortunately, once an epicardial device is implanted, the patient is no longer eligible to receive MRI exams due to an elevated risk of RF heating. Here we show that a simple modification in the trajectory of epicardial leads can substantially and reliably reduce RF heating during MRI at 1.5 T, with benefits extending to abandoned leads. MethodsElectromagnetic simulations were performed to assess RF heating of two common epicardial lead trajectories exhibiting different degrees of coupling with MRI incident electric fields. Experiments in anthropomorphic phantoms implanted with commercial cardiac implantable electronic devices (CIEDs) confirmed the findings. ResultsSimulations of an epicardial lead with a trajectory where the excess length of the lead was looped and placed on the anterior surface of the heart showed a 9-fold reduction in 0.1g-averaged SAR compared to the lead with excess length looped on the inferior surface of the heart. Repeated experiments with a commercial epicardial device confirmed the results, showing a 16-fold reduction in the average temperature rise for fully implanted systems with leads following low-SAR trajectories, and a 20-fold reduction in RF heating on an abandoned lead. ConclusionSurgical modification of epicardial lead trajectory can substantially reduce RF heating at 1.5 T, with benefits extending to abandoned leads.

biophysics↗

bioRxiv2021

Exploration of polyyne biosynthetic gene cluster diversity in bacteria leads to the discovery of the Pseudomonas polyyne protegencin

Natural products that possess alkyne or polyyne moieties have been isolated from a variety of biological sources. In bacteria their biosynthesis has been defined, however, the distribution of polyyne biosynthetic gene clusters (BGCs), and their evolutionary relationship to alkyne biosynthesis, have not been addressed. We explored the distribution of alkyne biosynthesis gene cassettes throughout bacteria, revealing evidence of multiple horizontal gene transfer events. Investigating the evolutionary connection between alkyne and polyyne biosynthesis identified a monophyletic clade possessing a conserved seven-gene cassette for polyyne biosynthesis. Mapping the diversity of these conserved genes revealed a phylogenetic clade representing a polyyne BGC in Pseudomonas, pgn, and subsequent pathway mutagenesis and analytical chemistry characterised the associated metabolite, protegencin. In addition to unifying and expanding our knowledge of polyyne diversity, our results show that alkyne and polyyne biosynthetic gene clusters are promiscuous within bacteria. Systematic mapping of conserved biosynthetic genes across bacterial genomic diversity has proven to be a successful method for discovering natural products.

microbiology↗

bioRxiv2020

Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores from Burkholderia gladioli

Burkholderia is a genus of diverse Gram-negative bacteria that includes several opportunistic pathogens. Siderophores, which transport iron from the environment into microbial cells, are important virulence factors in most pathogenic Burkholderia species. However, it is widely believed that Burkholderia gladioli, which can infect the lungs of cystic fibrosis (CF) sufferers, does not produce siderophores. B. gladioli BCC0238, isolated from the lung of a CF patient, produces two novel metabolites in a minimal medium containing glycerol and ribose as carbon sources. HPLC purification, followed by detailed spectroscopic analyses, identified these metabolites as unusual lipodepsipeptides containing a unique citrate-derived fatty acid and a rare dehydro-{beta}-alanine residue. The absolute configurations of the amino acid residues in the two metabolites was elucidated using Marfeys method and the gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of most B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S (CAS) assay showed the metabolites bind ferric iron and that this supresses their production when added to the growth medium. Moreover, a gene encoding a TonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes. Together, these observations suggest that these metabolites likely function as siderophores in B. gladioli.

microbiology↗

bioRxiv2020

Kill and cure: genomic phylogeny and bioactivity of a diverse collection of Burkholderia gladioli bacteria capable of pathogenic and beneficial lifestyles

Burkholderia gladioli is one of few bacteria with a broad ecology spanning disease in humans, animals, and plants, and encompassing beneficial interactions with multiple eukaryotic hosts. It is a plant pathogen, a bongkrekic acid toxin producing food-poisoning agent, and a lung pathogen in people with cystic fibrosis (CF). Contrasting beneficial traits include antifungal production exploited by insects to protect their eggs, plant protective abilities and antibiotic biosynthesis. We explored the ecological diversity and specialized metabolite biosynthesis of 206 B. gladioli strains, phylogenomically defining 5 evolutionary clades. Historical disease pathovars (pv) B. gladioli pv. allicola and B. gladioli pv. cocovenenans were phylogenetically distinct, while B. gladioli pv. gladioli and B. gladioli pv. agaricicola were indistinguishable. Soft-rot disease and CF infection pathogenicity traits were conserved across all pathovars. Biosynthetic gene clusters for toxoflavin, caryoynencin and enacyloxin were dispersed across B. gladioli, but bongkrekic acid and gladiolin production were clade specific. Strikingly, 13% of CF-infection strains characterised (n=194) were bongkrekic acid toxin positive, uniquely linking this food-poisoning risk factor to chronic lung disease. Toxin production was suppressed by exposing strains to the antibiotic trimethoprim, providing a potential therapeutic strategy to minimise poisoning risk in CF.

microbiology↗