Self-terminating re-entrant cardiac arrhythmias: quantitative characterization

Atrial and ventricular tachyarrhythmia are often sustained by re-entrant propagation, and explained by deterministic models. A quantitative, stochastic description of self-termination provides an alternative to the current paradigm for re-entrant tachyarrhythmia - that of triggers and a substrate, modelled by parametrically heterogeneous deterministic partial differential equations. Atrial and ventricular data was from recordings obtained during routine clinical monitoring and treatment, either noninvasively or invasively. Atrial and ventricular tachycardia are characterised by their initiation times and durations, re-presented as instantaneous rates, whose means estimate transition probabilities/s for onset and termination. These estimated probabilities range from 10(-9) to 10(-1)/s

Recent progress with hot carrier solar cells

Hot carrier solar cells offer one of the most promising options for high performance “third generation” photovoltaic devices. For successful operation, these need to be thin, strongly absorbing, radioactively efficient devices in a simple 2-terminal configuration. Nonetheless, they offer potential performance close to the maximum possible for solar conversion, equivalent to a multi-cell stack of six or more tandem cells possibly without some of the limitations, such as spectral sensitivity. However, hot carrier cells offer some quite fundamental challenges in implementation that our team is addressing in an internationally collaborative effort

Singlet Fission in Concentrated TIPS-Pentacene Solutions: The Role of Excimers and Aggregates

The excited-state dynamics of 6,13-bis(triisopropylsilylethynyl)pentacene is investigated to determine the role of excimer and aggregate formation in singlet fission in high-concentration solutions. Photoluminescence spectra were measured by excitation with the evanescent wave in total internal reflection, in order to avoid reabsorption effects. The spectra over nearly two magnitudes of concentration were nearly identical, with no evidence for excimer emission. Time-correlated single-photon counting measurements confirm that the fluorescence lifetime shortens with concentration. The observed rate constant grows at high concentrations, and this effect is modeled in terms of the hard-sphere radial distribution function. NMR measurements confirm that aggregation takes place with a binding constant of between 0.14 and 0.43 M-1. Transient absorption measurements are consistent with a diffusive encounter mechanism for singlet fission, with hints of more rapid singlet fission in aggregates at the highest concentration measured. These data show that excimers do not play the role of an emissive intermediate in exothermic singlet fission in solution and that, while aggregation occurs at higher concentrations, the mechanism of singlet fission remains dominated by diffusive encounters

Crystalline silicon solar cells with tetracene interlayers the path to silicon singlet fission heterojunction devices

Singlet exciton fission is an exciton multiplication process that occurs in certain organic materials, converting the energy of single highly-energetic photons into pairs of triplet excitons. This could be used to boost the conversion efficiency of crystalline silicon solar cells by creating photocurrent from energy that is usually lost to thermalisation. An appealing method of implementing singlet fission with crystalline silicon is to incorporate singlet fission media directly into a crystalline silicon device. To this end, we developed a solar cell that pairs the electron-selective contact of a high-efficiency silicon heterojunction cell with an organic singlet fission material, tetracene, and a PEDOT:PSS hole extraction layer. Tetracene and n-type crystalline silicon meet in a direct organic-inorganic heterojunction. In this concept the tetracene layer selectively absorbs blue-green light, generating triplet pairs that can dissociate or resonantly transfer at the organo-silicon interface, while lower-energy light is transmitted to the silicon absorber. UV photoemission measurements of the organic-inorganic interface showed an energy level alignment conducive to selective hole extraction from silicon by the organic layer. This was borne out by current-voltage measurements of devices subsequently produced. In these devices, the silicon substrate remained well-passivated beneath the tetracene thin film. Light absorption in the tetracene layer created a net reduction in current for the solar cell, but optical modelling of the external quantum efficiency spectrum suggested a small photocurrent contribution from the layer. This is a promising first result for the direct heterojunction approach to singlet fission on crystalline silicon

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial

\ua9 The Author(s) 2024.Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. Methods: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. Results: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43–2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29–0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). Conclusion: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF. Graphical Abstract: (Figure presented.)

Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).   Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p&lt;0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p&lt;0.001), alcohol intake (p = 0.003) and CRP (p&lt;0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p&lt;0.001).   Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP  Original Publication: Peter Garvin, Lennart Nilsson, John Carstensen, Lena Jonasson and Margareta Kristenson, Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population, 2008, PLoS ONE, (3), 3, e1774. http://dx.doi.org/10.1371/journal.pone.0001774 Licensee: Public Library of Science (PLoS) http://www.plos.org/</p

Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris

Objective: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). Methods: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. Results: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p,0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p,0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p,0.01. Conclusion: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that th

An Economic Evaluation of a Streamlined Day-Case Atrial Fibrillation Ablation Protocol and Conventional Cryoballoon Ablation versus Antiarrhythmic Drugs in a UK Paroxysmal Atrial Fibrillation Population

Background and Aims Symptom control for atrial fibrillation can be achieved by catheter ablation or drug therapy. We assessed the cost effectiveness of a novel streamlined atrial fibrillation cryoballoon ablation protocol (AVATAR) compared with optimised antiarrhythmic drug (AAD) therapy and a conventional catheter ablation protocol, from a UK National Health Service (NHS) perspective. Methods Data from the AVATAR study were assessed to determine the cost effectiveness of the three protocols in a two-step process. In the first stage, statistical analysis of clinical efficacy outcomes was conducted considering either a three-way comparison (AVATAR vs. conventional ablation vs. optimised AAD therapies) or a two-way comparison (pooled ablation protocol data vs. optimised AAD therapies). In the second stage, models assessed the cost effectiveness of the protocols. Costs and some of the clinical inputs in the models were derived from within-trial cost analysis and published literature. The remaining inputs were derived from clinical experts. Results No significant differences between the ablation protocols were found for any of the clinical outcomes used in the model. Results of a within-trial cost analysis show that AVATAR is cost-saving (£1279 per patient) compared with the conventional ablation protocol. When compared with optimised AAD therapies, AVATAR (pooled conventional and AVATAR ablation protocols efficacy) was found to be more costly while offering improved clinical benefits. Over a lifetime time horizon, the incremental cost-effectiveness ratio of AVATAR was estimated as £21,046 per quality-adjusted life-year gained (95% credible interval £7086–£71,718). Conclusions The AVATAR streamlined protocol is likely to be a cost-effective option versus both conventional ablation and optimised AAD therapy in the UK NHS healthcare setting