Spatial distribution of electrical reconnection after pulmonary vein isolation in patients with recurrent paroxysmal atrial fibrillation

Introduction

Recurrence of atrial fibrillation after pulmonary vein isolation (PVI) occurs frequently and may be associated with electrical reconnection of the pulmonary veins (PV). We investigated spatial distribution of electrical reconnection during re-do procedures in patients with paroxysmal atrial fibrillation who had previous successful acute electrical PVI with either single irrigated tip, antral ablation (s-RF; n = 38) or multi-electrode, duty-cycled ablation (PVAC; n = 48).

Methods and Results

EP navigator, mapping and irrigated tip ablation catheters were used in all re-do procedures. Sites of reconnection were assessed in a 12-segment model. Baseline clinical and demographic characteristics were similar in both groups. The number of PVs reconnected per patient was similar in both groups (2.9 ± 0.9 and 3.2 ± 0.7 (p = 0.193), s?RF and PVAC, respectively), and each PV was equally affected. However, the inferior quadrant of the right lower PV was significantly more vulnerable to reconnection after previous PVAC ablation, whereas the superior quadrant of the right upper PV showed significantly more reconnection in the s?RF group.

Conclusion

The overall number of PVs reconnected was equally high in both groups, and each PV was affected equally. However, there were significant differences in the spatial distribution of electrical reconnection. Better understanding of predilection sites for reconnection might help to improve the long-term success rate of PVI.

     

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.     

How Do General Practitioners Conceptualise Advance Care Planning in Their Practice? A Qualitative Study

ObjectivesTo explore how GPs conceptualise advance care planning (ACP), based on their experiences with ACP in their practice.MethodsFive focus groups were held with 36 GPs. Discussions were analysed using a constant comparative method.ResultsFour overarching themes in the conceptualisations of ACP were discerned: (1) the organisation of professional care required to meet patients’ needs, (2) the process of preparing for death and discussing palliative care options, (3) the discussion of care goals and treatment decisions, (4) the completion of advance directives. Within these themes, ACP was both conceptualised in terms of content of ACP and/or in terms of tasks for the GP. A specific task that was mentioned throughout the discussion of the four different themes was (5) the task of actively initiating ACP by the GP versus passively waiting for patients’ initiation.ConclusionsThis study illustrates that GPs have varying conceptualisations of ACP, of which some are more limited to specific aspects of ACP. A shared conceptualisation and agreement on the purpose and goals of ACP is needed to ensure successful implementation, as well as a systematic integration of ACP in routine practice that could lead to a better uptake of all the important elements of ACP.     

Evolution,plasticity and evolving plasticity of phenology in the tree species Alnus glutinosa

Both traits and the plasticity of these traits are subject to evolutionary change and therefore affect the long‐term persistence of populations and their role in local communities. We subjected clones from 12 different populations of Alnus glutinosa, located along a latitudinal gradient, to two different temperature treatments, to disentangle the distribution of genetic variation in timing of bud burst and bud burst plasticity within and among genotypes, populations, and regions. We calculated heritability and evolvability estimates for bud burst and bud burst plasticity and assessed the influence of divergent selection relative to neutral drift. We observed higher levels of heritability and evolvability for bud burst than for its plasticity, whereas the total phenological heritability and evolvability (i.e. combining timing of bud burst and bud burst plasticity) suggest substantial evolutionary potential with respect to phenology. Earlier bud burst was observed for the low‐latitudinal populations than for the populations from higher latitudes, whereas the high‐latitudinal populations did not show the expected delayed bud burst. This countergradient variation can be due to evolution towards increased phenological plasticity at higher latitudes. However, because we found little evidence for adaptive differences in phenological plasticity across the latitudinal gradient, we suggest differential frost tolerance as the most likely explanation for the observed phenological patterns in A. glutinosa.     

Twist and Degrade—Impact of Molecular Structure on the Photostability of Nonfullerene Acceptors and Their Photovoltaic Blends

Nonfullerene acceptors (NFAs) dominate organic photovoltaic (OPV) research due to their promising efficiencies and stabilities. However, there is very little investigation into the molecular processes of degradation, which is critical to guiding design of novel NFAs for long‐lived, commercially viable OPVs. Here, the important role of molecular structure and conformation in NFA photostability in air is investigated by comparing structurally similar but conformationally different promising NFAs: planar O‐IDTBR and nonplanar O‐IDFBR. A three‐phase degradation process is identified: i) initial photoinduced conformational change (i.e., torsion about the core–benzothiadiazole dihedral), induced by noncovalent interactions with environmental molecules, ii) followed by photo‐oxidation and fragmentation, leading to chromophore bleaching and degradation product formation, and iii) finally complete chromophore bleaching. Initial conformational change is a critical prerequisite for further degradation, providing fundamental understanding of the relative stability of IDTBR and IDFBR, where the already twisted IDFBR is more prone to degradation. When blended with the donor polymer poly(3‐hexylthiophene), both NFAs exhibit improved photostability while the photostability of the polymer itself is significantly reduced by the more miscible twisted NFA. The findings elucidate the important role of NFA molecular structure in photostability of OPV systems, and provide vital insights into molecular design rules for intrinsically photostable NFAs.     

Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors

Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC₅₀ values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (K_i = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.     

Non-rigid deformation to include subject-specific detail in musculoskeletal models of CP children with proximal femoral deformity and its effect on muscle and contact forces during gait

To account for proximal femoral deformities in children with cerebral palsy (CP), subject-specific musculoskeletal models are needed. Non-rigid deformation (NRD) deforms generic onto personalized bone geometry and thereby transforms the muscle points. The goal of this study was to determine to what extent the models and simulation outcomes in CP patients differ when including subject-specific detail using NRD or Magnetic Resonance Imaging (MRI)-based models. The NRD models slightly overestimated hip contact forces compared to MRI models and differences in muscle point positions and moment arm lengths (MALs) remained, although differences were smaller than for the generic model.