Advice to a Young Mathematical Biologist.

This paper offers advice to early-mid career researchers in Mathematical Biology from ten past and current Presidents of the Society for Mathematical Biology. The topics covered include deciding if a career in academia is right for you; finding and working with a mentor; building collaborations and working with those from other disciplines; formulating a research question; writing a paper; reviewing papers; networking; writing fellowship or grant proposals; applying for faculty positions; and preparing and giving lectures. While written with mathematical biologists in mind, it is hoped that this paper will be of use to early and mid career researchers across the mathematical, physical and life sciences, as they embark on careers in these disciplines.

Determinants of left atrial local impedance: Relationships with contact force, atrial fibrosis, and rhythm.

INTRODUCTION: The relationships between baseline tissue local impedance (LI), contact force (CF), atrial fibrosis, and atrial rhythm are uninvestigated in a clinical setting. We compared the relationship of LI and CF between atrial fibrillation (AF) and sinus rhythm (SR) accounting for the effects of atrial fibrosis as assessed by bipolar voltage and LI. METHODS: Patients undergoing persistent AF ablation were recruited. LI was recorded referenced to patient blood pool (LIr) and concurrent to changes in CF, with data collected at the same locations in AF and SR. RESULTS: Twenty patients were recruited. 109 locations were sampled obtaining 1903 data points (SR: 966, AF: 937). CF correlated strongly with LI (repeated measures correlation = 0.64). The relationship between CF and LIr was logarithmic. Rhythm and CF had a significant main (both p < .0005) and interaction effect (p = .022) on tissue LI: AF demonstrated higher LIr values than SR for similar CF. Bipolar voltage had no effect on the relationship of CF to LIr in either rhythm. Assessing fibrosis using LIr showed an interaction effect with CF for LIr in SR and AF, (SR: p < .0005, AF: p = .01), with increased fibrosis showing lesser change in LIr per gram of CF. CONCLUSIONS: CF and rhythm significantly affect the measured LIr of LA myocardium. Optimal catheter-tissue coupling may be better achieved with higher levels of CF and in AF rather than SR. Atrial fibrosis, as assessed by LIr but not bipolar voltage, affected the CF-LI relationship.

A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered with and without AS03 Adjuvant in Healthy US Adults.

INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China due to an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n=180), ages 19-50 years, were enrolled into this partially-blinded, randomized, multi-center Phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with two different boost intervals (21 versus 120 days) and two dosages (3.75 or 15 µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition (HAI) and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest HAI GMT (95%CI) observed against the 2017 A(H7N9) strain was 133.4 (83.6, 212.6) among participants who received homologous, adjuvanted 3.75 ug+AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. (NCT03589807).

Leadless pacemakers at 5-year follow-up: the Micra transcatheter pacing system post-approval registry.

BACKGROUND AND AIMS: Prior reports have demonstrated a favourable safety and efficacy profile of the Micra leadless pacemaker over mid-term follow-up; however, long-term outcomes in real-world clinical practice remain unknown. Updated performance of the Micra VR leadless pacemaker through five years from the worldwide post-approval registry (PAR) was assessed. METHODS: All Micra PAR patients undergoing implant attempts were included. Endpoints included system- or procedure-related major complications and system revision rate for any cause through 60 months post-implant. Rates were compared through 36 months post-implant to a reference dataset of 2667 transvenous pacemaker patients using Fine-Gray competing risk models. RESULTS: 1809 patients were enrolled between July 2015 and March 2018 and underwent implant attempts from 179 centres in 23 countries with a median follow-up period of 51.1 months (IQR: 21.6-64.2). The major complication rate at 60 months was 4.5% [95% confidence interval (CI): 3.6%-5.5%] and was 4.1% at 36 months, which was significantly lower than the 8.5% rate observed for transvenous systems (HR: .47, 95% CI: .36-.61; P < .001). The all-cause system revision rate at 60 months was 4.9% (95% CI: 3.9%-6.1%). System revisions among Micra patients were mostly for device upgrades (41.2%) or elevated thresholds (30.6%). There were no Micra removals due to infection noted over the duration of follow-up. At 36 months, the system revision rate was significantly lower with Micra vs. transvenous systems (3.2% vs. 6.6%, P < .001). CONCLUSIONS: Long-term outcomes with the Micra leadless pacemaker continue to demonstrate low rates of major complications and system revisions and an extremely low incidence of infection.

Role of routine investigations post cardiac devices implants in detecting peri-procedural complications: A retrospective analysis from a tertiary UK center.

BACKGROUND: Peri-procedural complications associated with cardiac implantable electronic devices are not uncommon. European Society of Cardiology guidelines recommend device checks of all devices within 72 h of implant. European Heart Rhythm Association expert practical guide on Cardiac implantable electronic devices (CIEDs) recommend that a chest x-ray (CXR) should be performed within 24 h to rule out pneumothorax and document lead positions. First, the rate of peri-procedural complications associated with CIED implants at our center, as well as patient and/or procedural-related factors that are associated with higher rates of complications, is analyzed. Second, the yield of the guideline-recommended measures in the early detection of peri-procedural complications is examined. MATERIALS AND METHODS: Consecutive de novo transvenous device implants at our center in 2019 were retrospectively analyzed. Patients' demographics, types and indications for device therapy, procedural reports, device checks, and CXRs were obtained from the hospital electronic records. RESULTS: A total of 578 patients (Age 74 ± 16 years, 68% male) were included. All patients had routine post-procedure CXRs and device checks. There were 16 (2.8%) complications; 7 (1.2%) pneumothoraxes, 6 (1%) pericardial effusions, and 3 (0.5%) lead displacements. Procedure time correlated significantly with complications; in uncomplicated cases it was 99 ± 43 min versus 127 ± 50 min in procedures associated with complications (p = .02). CONCLUSIONS: Routine post CIED implantation CXRs can detect early peri-procedural complications, while repeat post mobilization device checks has low yield of detection of complications. The only statistically significant predictor of peri-procedural complications is the duration of the procedure; longer procedures were associated with higher rates of complications.

An in situ digital synthesis strategy for the discovery and description of ocean life.

Revolutionary advancements in underwater imaging, robotics, and genomic sequencing have reshaped marine exploration. We present and demonstrate an interdisciplinary approach that uses emerging quantitative imaging technologies, an innovative robotic encapsulation system with in situ RNA preservation and next-generation genomic sequencing to gain comprehensive biological, biophysical, and genomic data from deep-sea organisms. The synthesis of these data provides rich morphological and genetic information for species description, surpassing traditional passive observation methods and preserved specimens, particularly for gelatinous zooplankton. Our approach enhances our ability to study delicate mid-water animals, improving research in the world's oceans.

Immunogenicity and safety of varying dosages of a fifth-wave influenza A/H7N9 inactivated vaccine given with and without AS03 adjuvant in healthy adults.

BACKGROUND: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated. METHODS: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant. RESULTS: Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19-64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events. CONCLUSIONS: AS03 adjuvant improved the immune responses to an inactivated fifth-wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies.

The Micra Transcatheter Pacing System: past, present and the future.

Leadless permanent pacemakers represent an important innovation in cardiac device developments. Although transvenous permanent pacemakers have become indispensable in managing bradyarrhythmia and saving numerous lives, the use of transvenous systems comes with notable risks tied to intravascular leads and subcutaneous pockets. This drawback has spurred the creation of leadless cardiac pacemakers. Within this analysis, we compile existing clinical literature and proceed to evaluate the efficacy and safety of the Micra Transcatheter Pacing System. We also delve into the protocols for addressing a malfunctioning or end-of-life Micra as well as device extraction. Lastly, we explore prospects in this domain, such as the emergence of entirely leadless cardiac resynchronization therapy-defibrillator devices.

What is Micra? Micra is a type of leadless pacemaker. Leadless pacemakers are a relatively recent breakthrough in medical science. Regular pacemakers have wires that run into the heart and a battery tucked under the skin. They are crucial for treating slow heartbeats. However, they carry risks tied to the wire or batteries. The Micra is placed in the heart using a tiny cut near the groin. There is no wire left behind in the body. Using Micra can avoid the potential complications linked to regular pacemakers. Is Micra safe & effective? Scientists have found that Micra is effective in patients with appropriate heart rhythm issues. There seem to be fewer complications compared to the regular pacemakers. What does the future hold for Micra? There are concerns about what to do when the battery runs out. The technology and batteries in Micra are getting better. It is expected Micra will be used even more in the future.

Comparison of voltages between atria: differences in sinus rhythm and atrial fibrillation.

BACKGROUND: Ultra high-density mapping systems allow for comparison of atrial electroanatomical maps in unprecedented detail. Atrial scar determined by voltages and surface area between atria, rhythm and atrial fibrillation (AF) types was assessed. METHODS: Left (LA) and right atrial (RA) maps were created using Rhythmia HDx in patients listed for ablation for paroxysmal (PAF, sinus rhythm (SR) maps only) or persistent AF (PeAF, AF and SR maps). Electrograms on corresponding SR/AF maps were paired for direct comparison. Percentage surface area of scar was assigned low- (LVM, ≤ 0.05 mV), intermediate- (IVM, 0.05-0.5 mV) or normal voltage myocardium, (NVM, > 0.5 mV). RESULTS: Thirty-eight patients were recruited generating 96 maps using 913,480 electrograms. Paired SR-AF bipolar electrograms showed fair correlation in LA (Spearman's ρ = 0.32) and weak correlation in RA (ρ = 0.19) and were significantly higher in SR in both (LA: 0.61 mV (0.20-1.67) vs 0.31 mV (0.10-0.74), RA: 0.68 mV (0.19-1.88) vs 0.47 mV (0.14-1.07), p < 0.0005 both). Voltages were significantly higher in patients with PAF over PeAF, (LA: 1.13 mV (0.39-2.93) vs 0.52 mV (0.16-1.49); RA: 0.93 mV (0.24-2.46) vs 0.57 mV (0.17-1.69)). Minimal differences were seen in electrogram voltages between atria. Significantly more IVM/LVM surface areas were seen in AF over SR (LA only, p < 0005), and PeAF over PAF (LA: p = 0.01, RA: p = 0.04). There was minimal difference between atria within patients. CONCLUSIONS: Ultra high-density mapping shows paired electrograms correlate poorly between SR and AF. SR electrograms are typically (but not always) larger than those in AF. Patients with PeAF have a lower global electrogram voltage than those with PAF. Electrogram voltages are similar between atria within individual patients.

Theorising Evidence Law.

What does it mean for a specialist department of legal studies, such as the Law of Evidence, to have, or to acquire, 'philosophical foundations'? In what sense are the theoretical foundations of procedural scholarship and teaching distinctively or uniquely philosophical? The publication of Philosophical Foundations of Evidence Law (OUP, 2021), edited by Christian Dahlman, Alex Stein and Giovanni Tuzet, presents a valuable opportunity to reflect on these existential questions of disciplinary constitution, methodology and design. This review article critically examines the volume's idiosyncratic selection of topics, structural taxonomy, epistemological priorities, and enigmatic thesis that modern evidence law is turning from rules to reasons as its organising intellectual framework. Whilst the volume is impressively interdisciplinary and cosmopolitan in authorship and outlook, some doubts are expressed about its implicit US orientation, limited engagement with institutional or doctrinal details, and marginalisation of normative criminal jurisprudence.

Leadless Pacemakers: Current Achievements and Future Perspectives.

Despite the technological advances in pacemaker technology, the transvenous implanted leads are still considered the Achilles' heel of this rhythm-control therapy. The leadless permanent pacemaker system was developed as an option to bypass the weakness of the transvenous approach. Advances in battery technology and deep miniaturisation of electronics now offer the opportunity to implant the whole pacemaker system into the right ventricle. This review aims to provide a comprehensive report on the advent of leadless pacemakers, their clinical usefulness and the future perspectives of this disruptive and promising technology. Further research is required before some of these technologies are safely and routinely used in clinical practice.

Personalized driving safety: Using telematics to reduce risky driving behaviour among young drivers.

INTRODUCTION: The role of real-time data capture (via telematics technology) is gathering prominence as a strategy to provide feedback to young drivers about important road safety issues. METHOD: A naturalistic driving study was undertaken to determine whether providing personalized feedback (via a smartphone app) to young provisional drivers aged 17-20 years living in metropolitan and regional Western Australia (WA) reduced their risky driving behavior compared to a control group who did not receive feedback. Speeding over the posted speed limit, harsh decelerations (braking), harsh accelerations and overall driving performance, were recorded continuously using the smartphone app during the 11-week study. Four separate Generalised Estimating Equations (GEE) linear regression models were undertaken after accounting for relevant confounders including driving exposure to determine the difference between the intervention and control group for the 4 driving outcomes obtained from the smartphone app. RESULTS: The study found that there was no significant change in overall driving scores between the intervention and control groups (p = 0.35). However, the overall driving score significantly improved by 0.19 points for young provisional drivers who lived in regional areas compared to those in the metropolitan area (p = 0.05) after adjusting for potential confounders. There was also no significant change in harsh braking scores (p = 0.46) and harsh acceleration scores between the intervention and control groups (p = 0.26) However, harsh acceleration scores improved by 0.37 points for females compared to males (p = 0.04). Lastly, there was no significant change in speed scores between the control and intervention groups (p = 0.72). However, the speed scores of participants who lived in regional WA improved by 0.22 points compared to those in the metropolitan area (p = 0.02). Furthermore, for every 1,000 km travelled, speed scores worsened by -0.08 points (p < 0.01) regardless of group. CONCLUSIONS: The study did not find any statistical difference in the driving outcomes examined; however the treatment effects for feedback were consistently in the expected positive direction. Young drivers in regional WA also improved their speeding scores and overall driving performance scores compared to young drivers in the metropolitan area. Females, also significantly improved their harsh deceleration scores compared to males, regardless of group allocation. These results highlight the use of smartphone telematics as an opportunity to not only enhance the safety of provisional young drivers but also provide data-informed decision making and policy development.

Birds multiplex spectral and temporal visual information via retinal On- and Off-channels.

In vertebrate vision, early retinal circuits divide incoming visual information into functionally opposite elementary signals: On and Off, transient and sustained, chromatic and achromatic. Together these signals can yield an efficient representation of the scene for transmission to the brain via the optic nerve. However, this long-standing interpretation of retinal function is based on mammals, and it is unclear whether this functional arrangement is common to all vertebrates. Here we show that male poultry chicks use a fundamentally different strategy to communicate information from the eye to the brain. Rather than using functionally opposite pairs of retinal output channels, chicks encode the polarity, timing, and spectral composition of visual stimuli in a highly correlated manner: fast achromatic information is encoded by Off-circuits, and slow chromatic information overwhelmingly by On-circuits. Moreover, most retinal output channels combine On- and Off-circuits to simultaneously encode, or multiplex, both achromatic and chromatic information. Our results from birds conform to evidence from fish, amphibians, and reptiles which retain the full ancestral complement of four spectral types of cone photoreceptors.

A gradient mapping guided explainable deep neural network for extracapsular extension identification in 3D head and neck cancer computed tomography images.

BACKGROUND: Diagnosis and treatment management for head and neck squamous cell carcinoma (HNSCC) is guided by routine diagnostic head and neck computed tomography (CT) scans to identify tumor and lymph node features. The extracapsular extension (ECE) is a strong predictor of patients' survival outcomes with HNSCC. It is essential to detect the occurrence of ECE as it changes staging and treatment planning for patients. Current clinical ECE detection relies on visual identification and pathologic confirmation conducted by clinicians. However, manual annotation of the lymph node region is a required data preprocessing step in most of the current machine learning-based ECE diagnosis studies. PURPOSE: In this paper, we propose a Gradient Mapping Guided Explainable Network (GMGENet) framework to perform ECE identification automatically without requiring annotated lymph node region information. METHODS: The gradient-weighted class activation mapping (Grad-CAM) technique is applied to guide the deep learning algorithm to focus on the regions that are highly related to ECE. The proposed framework includes an extractor and a classifier. In a joint training process, informative volumes of interest (VOIs) are extracted by the extractor without labeled lymph node region information, and the classifier learns the pattern to classify the extracted VOIs into ECE positive and negative. RESULTS: In evaluation, the proposed methods are well-trained and tested using cross-validation. GMGENet achieved test accuracy and area under the curve (AUC) of 92.2% and 89.3%, respectively. GMGENetV2 achieved 90.3% accuracy and 91.7% AUC in the test. The results were compared with different existing models and further confirmed and explained by generating ECE probability heatmaps via a Grad-CAM technique. The presence or absence of ECE has been analyzed and correlated with ground truth histopathological findings. CONCLUSIONS: The proposed deep network can learn meaningful patterns to identify ECE without providing lymph node contours. The introduced ECE heatmaps will contribute to the clinical implementations of the proposed model and reveal unknown features to radiologists. The outcome of this study is expected to promote the implementation of explainable artificial intelligence-assiste ECE detection.

Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.

Design and rationale of the MODULAR ATP global clinical trial: A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. Objective: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. Methods: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER™ Modular Pacing System and EMBLEM™ Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. Results: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. Conclusion: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

Imaging Spectrum of the Developing Glioblastoma: A Cross-Sectional Observation Study.

Glioblastoma (GBM) has the typical radiological appearance (TRA) of a centrally necrotic, peripherally enhancing tumor with surrounding edema. The objective of this study was to determine whether the developing GBM displays a spectrum of imaging changes detectable on routine clinical imaging prior to TRA GBM. Patients with pre-operative imaging diagnosed with GBM (1 January 2014-31 March 2022) were identified from a neuroscience center. The imaging was reviewed by an experienced neuroradiologist. Imaging patterns preceding TRA GBM were analyzed. A total of 76 out of 555 (14%) patients had imaging preceding TRA GBM, 57 had solitary lesions, and 19 had multiple lesions (total = 84 lesions). Here, 83% of the lesions had cortical or cortical/subcortical locations. The earliest imaging features for 84 lesions were T2 hyperintensity/CT low density (n = 18), CT hyperdensity (n = 51), and T2 iso-intensity (n = 15). Lesions initially showing T2 hyperintensity/CT low density later showed T2 iso-intensity. When CT and MRI were available, all CT hyperdense lesions showed T2 iso-intensity, reduced diffusivity, and the following enhancement patterns: nodular 35%, solid 29%, none 26%, and patchy peripheral 10%. The mean time to develop TRA GBM from T2 hyperintensity was 140 days and from CT hyperdensity was 69 days. This research suggests that the developing GBM shows a spectrum of imaging features, progressing through T2 hyperintensity to CT hyperdensity, T2 iso-intensity, reduced diffusivity, and variable enhancement to TRA GBM. Red flags for non-TRA GBM lesions are cortical/subcortical CT hyperdense/T2 iso-intense/low ADC. Future research correlating this imaging spectrum with pathophysiology may provide insight into GBM growth patterns.

Defibrillation Threshold Testing for Right-sided Device Implants: A Review to Inform Shared Decision-making, in Association with the British Heart Rhythm Society.

Prevention of sudden death using ICDs requires the reliable delivery of a high-energy shock to successfully terminate VF. Until more recently, the device implant procedure included conducting defibrillation threshold (DFT) testing involving VF induction and shock delivery to ensure efficacy. Large clinical trials, including SIMPLE and NORDIC ICD, have subsequently demonstrated that this is unnecessary, with a practice of omitting DFT testing having no impact on subsequent clinical outcomes. However, these studies specifically excluded patients requiring devices implanted on the right side, in whom the shock vector is significantly different and smaller studies suggest a higher DFT. In this review, the data regarding the use of DFT testing, focusing on right-sided implants, and the results of a survey of current UK practice are presented. In addition, a strategy of shared decision-making when it comes to deciding on the use of DFT testing during right-sided ICD implant procedures is proposed.

Preclinical cardiac perforation reduction in leadless pacing: An update to the Micra leadless pacemaker delivery system.

BACKGROUND: Leadless pacemakers have been developed to avoid some of the complications that are associated transvenous pacemakers. Pericardial effusion is a rare complication of leadless pacemaker implantation, which may result from perforation of the delivery catheter. In this study, we describe preclinical perforation performance of an updated Micra delivery catheter. METHODS: To assess preclinical perforation performance of the updated delivery catheter, three analyses were performed. First, Finite Element Analysis (FEA) computational modeling was performed to estimate the target tissue stress during Micra delivery catheter tenting. Second, benchtop perforation forces of ovine tissue were recorded for the original and updated delivery catheters. Finally, a Monte-Carlo simulation combining human cadaveric Micra implant forces and human ventricular tissue perforation properties was performed to estimate clinical perforation performance. RESULTS: FEA modeling demonstrated a 66% reduction in target tissue stress when using the updated Micra delivery catheter (6.2 vs. 2.2 psi, Original vs. Updated Micra delivery catheter). Updated Micra delivery catheters required 20% more force to perforate porcine ventricular tissues in benchtop testing (µupd  = 26.9N vs. µorg  = 22.4N, p = .01). Monte-Carlo Simulation of catheter performance in human cadaveric tissues predicts 28.5% reduction of catheter-perforated cases with the updated delivery catheter. CONCLUSIONS: This study, using computer modelling and benchtop experimentation, has indicated that increased surface area and rounding of the updated Micra catheter tip significantly improves preclinical perforation performance. It will be important to evaluate the impact of these catheter design changes with robust registry data.