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Introduction: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. Background: Studies on catheter ablation of AF may benefit from well‐described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost‐effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. Methods: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials. Results: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm‐related and other endpoints. Conclusion: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology. Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. [ABSTRACT FROM AUTHOR]

Aims: Remote monitoring (RM) of thoracic impedance represents an early marker of pulmonary congestion in heart failure (HF). Chronic kidney disease (CKD) may promote fluid overload in HF patients. We investigated whether concomitant CKD affected the efficacy of impedance‐based RM in the OptiLink HF trial. Methods and results: Among HF patients included in the OptiLink HF trial, time to the first cardiovascular hospitalization and all‐cause death according to the presence of concomitant CKD was analysed. CKD was defined as GFR < 60 mL/min/1.73 m2 at enrolment. Of the 1002 patients included in OptiLink HF, 326 patients (33%) had HF with concomitant CKD. The presence of CKD increased transmission of telemedical alerts (median of 2 (1‐5) vs. 1 (0–3); P = 0.012). Appropriate contacting after alert transmission was equally low in patients with and without CKD (57% vs. 59%, P = 0.593). The risk of the primary endpoint was higher in patients with CKD compared with patients without CKD (hazard ratio (HR), 1.62 [95% confidence interval (CI), 1.16–2.28]; P = 0.005). Impedance‐based RM independently reduced primary events in HF patients with preserved renal function, but not in those with CKD (HR 0.68 [95% CI, 0.52–0.89]; P = 0.006). Conclusions: The presence of CKD in HF patients led to a higher number of telemedical alert transmissions and increased the risk of the primary endpoint. Inappropriate handling of alert transmission was commonly observed in patients with chronic HF and CKD. Guidance of HF management by impedance‐based RM significantly decreased primary event rates in patients without CKD, but not in patients with CKD. [ABSTRACT FROM AUTHOR]

Environmental variation is increasingly recognized as an important driver of diversity in marine species despite the lack of physical barriers to dispersal and the presence of pelagic stages in many taxa. A robust understanding of the genomic and ecological processes involved in structuring populations is lacking for most marine species, often hindering management and conservation action. Cunner (Tautogolabrus adspersus) is a temperate reef fish with both pelagic early life‐history stages and strong site‐associated homing as adults; the species is also of interest for use as a cleaner fish in salmonid aquaculture in Atlantic Canada. We aimed to characterize genomic and geographic differentiation of cunner in the Northwest Atlantic. To achieve this, a chromosome‐level genome assembly for cunner was produced and used to characterize spatial population structure throughout Atlantic Canada using whole‐genome sequencing. The genome assembly spanned 0.72 Gbp and 24 chromosomes; whole‐genome sequencing of 803 individuals from 20 locations from Newfoundland to New Jersey identified approximately 11 million genetic variants. Principal component analysis revealed four regional Atlantic Canadian groups. Pairwise FST and selection scans revealed signals of differentiation and selection at discrete genomic regions, including adjacent peaks on chromosome 10 across multiple pairwise comparisons (i.e. FST 0.5–0.75). Redundancy analysis suggested association of environmental variables related to benthic temperature and oxygen range with genomic structure. Results suggest regional scale diversity in this temperate reef fish and can directly inform the collection and translocation of cunner for aquaculture applications and the conservation of wild populations throughout the Northwest Atlantic. [ABSTRACT FROM AUTHOR]

Lumpfish, Cyclopterus lumpus, have historically been harvested throughout Atlantic Canada and are increasingly in demand as a solution to controlling sea lice in Atlantic salmon farms—a process which involves both the domestication and the transfer of lumpfish between geographic regions. At present, little is known regarding population structure and diversity of wild lumpfish in Atlantic Canada, limiting attempts to assess the potential impacts of escaped lumpfish individuals from salmon pens on currently at‐risk wild populations. Here, we characterize the spatial population structure and genomic‐environmental associations of wild populations of lumpfish throughout the Northwest Atlantic using both 70K SNP array data and whole‐genome re‐sequencing data (WGS). At broad spatial scales, our results reveal a large environmentally associated genetic break between the southern populations (Gulf of Maine and Bay of Fundy) and northern populations (Newfoundland and the Gulf of St. Lawrence), linked to variation in ocean temperature and ice cover. At finer spatial scales, evidence of population structure was also evident in a distinct coastal group in Newfoundland and significant isolation by distance across the northern region. Both evidence of consistent environmental associations and elevated genome‐wide variation in FST values among these three regional groups supports their biological relevance. This study represents the first extensive description of population structure of lumpfish in Atlantic Canada, revealing evidence of broad and fine geographic scale environmentally associated genomic diversity. Our results will facilitate the commercial use of lumpfish as a cleaner fish in Atlantic salmon aquaculture, the identification of lumpfish escapees, and the delineation of conservation units of this at‐risk species throughout Atlantic Canada. [ABSTRACT FROM AUTHOR]

Post‐translational modifications by ubiquitin‐like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin‐related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin‐like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3‐independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4‐Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes. Synopsis: The ancient ubiquitin‐like protein Urm1 is a sulfur carrier protein for tRNA thiolation, but can also conjugate to target proteins. Here, analysis of the underlying molecular mechanisms reveals that Urm1 attachment simultaneously leads to the persulfidation of cysteines in target proteins, which may protect them from oxidative damage. In vitro ubiquitin‐like conjugation by Urm1 does not require E2 conjugation enzymes or E3 ligases.Urm1 conjugation depends on a peroxidatic cysteine in the target protein and the proximity of lysine, serine or threonine residues.Sulfur transfer from the thiocarboxylated C‐terminus of Urm1 onto cysteines in the target proteins is a mechanistic consequence of the urmylation reaction.High‐resolution crystal structure of an urmylated target protein directly shows formation of an iso‐peptide bond as well as cysteine persulfidation.The Urm1 pathway represents a distinct cysteine persulfidation pathway upon oxidative stress. [ABSTRACT FROM AUTHOR]

Sympatric adaptive phenotypic divergence should be underlain by genomic differentiation between subpopulations. When divergence drives similar patterns of phenotypic and ecological variation within species we expect evolution to draw on common allelic variation. We investigated divergence histories and genomic signatures of adaptive divergence between benthic and pelagic morphs of Icelandic Arctic charr. Divergence histories for each of four populations were reconstructed using coalescent modelling and 14,187 single nucleotide polymorphisms. Sympatric divergence with continuous gene flow was supported in two populations while allopatric divergence with secondary contact was supported in one population; we could not differentiate between demographic models in the fourth population. We detected parallel patterns of phenotypic divergence along benthic‐pelagic evolutionary trajectories among populations. Patterns of genomic differentiation between benthic and pelagic morphs were characterized by outlier loci in many narrow peaks of differentiation throughout the genome, which may reflect the eroding effects of gene flow on nearby neutral loci. We then used genome‐wide association analyses to relate both phenotypic (body shape and size) and ecological (carbon and nitrogen stable isotopes) variation to patterns of genomic differentiation. Many peaks of genomic differentiation were associated with phenotypic and ecological variation in the three highly divergent populations, suggesting a genomic basis for adaptive divergence. We detected little evidence for a parallel genomic basis of differentiation as most regions and outlier loci were not shared among populations. Our results show that adaptive divergence can have varied genomic consequences in populations with relatively recent common origins, similar divergence histories, and parallel phenotypic divergence. [ABSTRACT FROM AUTHOR]

Objective: This study examined the influence of surface contamination during repair procedures with hydrofluoric acid, silane, or ammonium polyfluoride on the bond strength of universal adhesives to dentin using different etching modes before and after thermocycling. Materials and Methods: Dentin surfaces of human molars were contaminated in different ways (silane, hydrofluoric acid, ammonium polyfluoride, and no pretreatment as control) followed by application of a universal adhesive (etch & rinse or self‐etch mode). After a composite build‐up was placed onto each tooth, sticks for the microtensile bond strength (MTBS) test were sectioned. Half of the sticks were tested after water storage for 24 h, the other half after thermocycling (15,000 cycles, 5/55°C). The MTBS data were analyzed statistically by using the Kolmogorov–Smirnov test, one‐way analysis of variance, and Tukey HSD test (p < 0.05). The fracture patterns of all specimens were evaluated and analyzed using a χ2 test. Results: Dentin contamination with a multifunctional silane does not influence microtensile bond strength irrespective of aging. Contamination with hydrofluoric acid or an ammonium polyfluoride primer leads to a significantly lower bond strength after aging, irrespective of the etch mode. Conclusion: Dentin contamination with hydrofluoric acid or ammonium polyfluorides during repair procedures should be avoided, as they appear to decrease the bond strength of universal adhesives. [ABSTRACT FROM AUTHOR]

Teleosts exhibit extensive diversity of sex determination (SD) systems and mechanisms, providing the opportunity to study the evolution of SD and sex chromosomes. Here we sequenced the genome of the common lumpfish (Cyclopterus lumpus Linnaeus), a species of increasing importance to aquaculture, and identified the SD region and master SD locus using a 70 K single nucleotide polymorphism array and tissue‐specific expression data. The chromosome‐level assembly identified 25 diploid chromosomes with a total size of 572.89 Mb, a scaffold N50 of 23.86 Mb and genome annotation‐predicted 21,480 protein‐coding genes. Genome‐wide association analysis located a highly sex‐associated region on chromosome 13, suggesting that anti‐Müllerian hormone (AMH) is the putative SD factor. Linkage disequilibrium and heterozygosity across chromosome 13 support a proto‐XX/XY system, with an absence of widespread chromosome divergence between sexes. We identified three copies of AMH in the lumpfish primary and alternate haplotype assemblies localized in the SD region. Comparison to sequences from other teleosts suggested a monophyletic relationship and conservation within the Cottioidei. One AMH copy showed similarity to AMH/AMHY in a related species and was also the only copy with expression in testis tissue, suggesting this copy may be the functional copy of AMH in lumpfish. The two other copies arranged in tandem inverted duplication were highly similar, suggesting a recent duplication event. This study provides a resource for the study of early sex chromosome evolution and novel genomic resources that benefits lumpfish conservation management and aquaculture. [ABSTRACT FROM AUTHOR]

Background: Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long‐term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla‐protein, an important vitamin K‐dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K‐dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT). Methods: The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two‐arm, open‐label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre‐existent coronary calcification. The development of CVC will be assessed by follow‐up CT at 12 and 24 months. Results: In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years. [ABSTRACT FROM AUTHOR]

Summary: Nodule microbiota are dominated by symbiotic nitrogen‐fixing rhizobia, however, other non‐rhizobial bacteria also colonise this niche. Although many of these bacteria harbour plant‐growth‐promoting functions, it is not clear whether these less abundant nodule colonisers impact root–nodule symbiosis.We assessed the relationship between the nodule microbiome and nodulation as influenced by the soil microbiome, by using a metabarcoding approach to characterise the communities inside nodules of healthy and starved Lotus species. A machine learning algorithm and network analyses were used to identify nodule bacteria of interest, which were re‐inoculated onto plants in controlled conditions to observe their potential functionality.The nodule microbiome of all tested species differed according to inoculum, but only that of Lotus burttii varied with plant health. Amplicon sequence variants representative of Pseudomonas species were the most indicative non‐rhizobial signatures inside healthy L. burttii nodules and negatively correlated with Rhizobium sequences. A representative Pseudomonas isolate co‐colonised nodules infected with a beneficial Mesorhizobium, but not with an ineffective Rhizobium isolate and another even reduced the number of ineffective nodules induced on Lotus japonicus.Our results show that nodule endophytes influence the overall outcome of the root–nodule symbiosis, albeit in a plant host‐specific manner. [ABSTRACT FROM AUTHOR]

Background: Registry data add important information to randomized controlled trials (RCT) on real‐life aspects of implantable cardioverter‐defibrillator (ICD) patients with and without cardiac resynchronization therapy (CRT‐D). This analysis of the prospectively conducted German Device Registry aims at comparing mortality rates, comorbidities, complication rates to results from RCT. Methods: The German Device registry (DEVICE) prospectively collected data on ICD and CRT‐D first implantations from 50 German centres. Demographic data, details on cardiac disease, electrocardiogram (ECG), medication, and data about procedure, complications, and hospital stay were stored in electronic case report forms. One year after device implantation patients were contacted for follow‐up. Results: DEVICE included n = 4384 first ICD/CRT‐D implantations (29.3% CRT‐D devices). We found a strong adherence to guidelines with over 90% of patients being on ß‐blocker and ACE‐inhibitor medication and adequate QRS width in the majority of CRT‐D patients. Patients receiving a CRT‐D were older (67.6 ± 11.0 years vs. 63.9 ± 13.4 years, p <.001) and had lower ejection fractions (mean 25% vs. 30%, p <.001) compared to ICD patients. Dilated cardiomyopathy was the predominant underlying heart disease in CRT‐D (53.3%), coronary artery disease in ICD patients (64.7%). Compared to RCT our DEVICE patients had more comorbidities (17.9% chronic kidney disease [CKD]) and higher 1‐year mortality rates (10.7% ICD group, 12.3% CRT group). In multivariate analysis, CKD patients had an almost 2‐fold higher risk of 1‐year mortality. Conclusion: Despite relevant limitations of registry data, DEVICE highlights important differences between RCT and real‐world registry data and the impact of comorbidities on mortality of ICD and CRT‐D recipients. [ABSTRACT FROM AUTHOR]

Aims: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF). Methods and results: The MEMS‐HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS‐HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non‐users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan‐treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non‐loop diuretics (P = 0.21). Conclusions: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes. [ABSTRACT FROM AUTHOR]

Data on the optimal treatment strategy for antiarrhythmic drug therapy (AAD) after catheter ablation for atrial fibrillation (AF) are inconsistent. The present study investigates whether postinterventional AAD leads to an improved long-term outcome. Patients from the prospective German Ablation Registry (n = 3275) discharged with or without AAD after catheter ablation for AF were compared regarding the rates of recurrences, reablations and cardiovascular events as well as patient reported outcomes during 12 months follow-up. In patients with paroxysmal AF (n = 2138) the recurrence rate did not differ when discharged with (n = 1051) or without (n = 1087) AAD (adjusted odds ratio (OR) 1.13, 95% confidence interval (CI) [0.95–1.35]). The reablation rate was higher and reduced treatment satisfaction was reported more often in those discharged with AAD (reablation: OR 1.30, 95% CI [1.05–1.61]; reduced treatment satisfaction: OR 1.76, 95% CI [1.20–2.58]). Similar rates of recurrences, reablations and treatment satisfaction were found in patients with persistent AF (n = 1137) discharged with (n = 641) or without (n = 496) AAD (recurrence: OR 1.22, 95% CI [0.95–1.56]; reablation: OR 1.21, 95% CI [0.91–1.61]; treatment satisfaction: OR 1.24, 95% CI [0.74–2.08]). The incidence of cardiovascular events and mortality did not differ at follow-up in patients discharged with or without AAD. In conclusion, the rates of recurrences, cardiovascular events and mortality did not differ between patients discharged with or without AAD after AF catheter ablation. However, AAD should be considered carefully in patients with paroxysmal AF, in whom it was associated with a higher reablation rate and reduced treatment satisfaction. Clinical trial registration: The trial has been registered under the number NCT01197638. [ABSTRACT FROM AUTHOR]

Introduction: Gender‐based differences in atrial fibrillation have been identified, but limited data exist for patients undergoing left atrial appendage occluder (LAAO) implantation. This study reports gender‐related periprocedural and 1‐year outcomes of the prospective, multicenter German left atrial appendage occlusion registry (LAARGE). Methods: LAARGE enrolled 641 patients who were scheduled for LAAO implantation from July 2014 to January 2016 in 38 hospitals in Germany. The data collected included demographics, clinical characteristics, details of implantation, and outcome. Efficacy and safety at 1‐year follow‐up were assessed by the occurrence of thrombembolic and bleeding events, as well as mortality. Results: Of 638 patients undergoing LAAO implantation 38.9% were female and 61.1% male. Females were older (76.4 ± 8.2 [females] vs. 75.6 ± 7.7 [males], p =.042) and had a higher stroke risk (CHA2DS2‐VASc score: 4.9 ± 1.5 vs. 4.3 ± 1.5, p <.001). In contrast, males suffered more often from coronary artery (33.1% vs. 53.8%, p <.001) and vascular disease (18.5% vs. 31.0%, p <.001). Technical success was high and similar for both genders (98.4% vs. 97.2%, p =.33). Severe periprocedural complications (6.9% vs. 3.1%, p =.032) occurred more often in females. At 1‐year follow‐up the rates of all‐cause stroke (0.5% vs. 1.3%, p =.65) and severe bleeding (0.0% and 1.0%, p =.29) were low and comparable between the genders. Also, one‐year all‐cause mortality (9.2% vs. 13.1%, p =.14) did not differ significantly. Conclusion: LAARGE documented in this elderly patient population undergoing LAAO implantation a higher rate of severe periprocedural complications in females. At 1‐year follow‐up similar efficacy and safety outcomes were observed for both genders. [ABSTRACT FROM AUTHOR]

Background: The impact of basic atrial rhythm (sinus rhythm [SR] vs. atrial fibrillation [AF]) during AF ablation on efficacy and safety is unknown. Methods: About 3375 patients from the German Ablation Registry undergoing first‐time AF ablation were divided according to the type of AF and the basic atrial rhythm during the ablation procedure: paroxysmal AF (PAF) and SR [group Ia], PAF and AF [group Ib]), persistent AF and SR (IIa), and persistent AF and AF (IIb). Results: Patients in SR (n = 2312 [67%]) underwent cryoballoon ablation more often (Ia vs. Ib p =.002 and IIa vs. IIb p =.010, whereas in patients in AF (n = 1063 [33%]) radiofrequency (RF)‐based ablation (Ia vs. Ib p =.006 and IIa vs. IIb p =.014) including left and/or right atrial substrate modification was more frequently performed. Depending on the basic rhythm there was no difference regarding arrhythmia recurrence during long‐term follow‐up. For patients suffering from persistent AF acute procedure‐related complications were more often documented when ablated in AF (9.1% vs. 4.6%, p =.012). which was mainly driven by the higher occurrence of pericardial effusion/tamponade. For patients suffering from persistent AF, favorable results were found regarding 366‐day Kaplan–Meier estimates of the incidence of MACCE (death, myocardial infarction, and stroke; p =.011) and the composite endpoint of death, myocardial infarction, stroke, and major bleeding (p =.006), when ablated in SR. Conclusion: Basic atrial rhythm at the time of AF ablation did not affect long‐term rhythm outcome. For patients suffering from persistent AF a more favorable acute and long‐term safety profile was observed when ablated in SR. [ABSTRACT FROM AUTHOR]

Conceptual models of adaptive divergence and ecological speciation in sympatry predict differential resource use, phenotype–environment correlations, and reduced gene flow among diverging phenotypes. While these predictions have been assessed in past studies, connections among them have rarely been assessed collectively. We examined relationships among phenotypic, ecological, and genetic variation in Arctic charr (Salvelinus alpinus) from six Icelandic localities that have undergone varying degrees of divergence into sympatric benthic and pelagic morphs. We characterized morphological variation with geometric morphometrics, tested for differential resource use between morphs using stable isotopes, and inferred the amount of gene flow from single nucleotide polymorphisms. Analysis of stable isotopic signatures indicated that sympatric morphs showed similar difference in resource use across populations, likely arising from the common utilization of niche space within each population. Carbon isotopic signature was also a significant predictor of individual variation in body shape and size, suggesting that variation in benthic and pelagic resource use is associated with phenotypic variation. The estimated percentage of hybrids between sympatric morphs varied across populations (from 0% to 15.6%) but the majority of fish had genotypes (ancestry coefficients) characteristic of pure morphs. Despite evidence of reduced gene flow between sympatric morphs, we did not detect the expected negative relationship between divergence in resource use and gene flow. Three lakes showed the expected pattern, but morphs in the fourth showed no detectable hybridization and had relatively low differences in resource use between them. This coupled with the finding that resource use and genetic differentiation had differential effects on body shape variation across populations suggests that reproductive isolation maintains phenotypic divergence between benthic and pelagic morphs when the effects of resource use are relatively low. Our ability to assess relationships between phenotype, ecology, and genetics deepens our understanding of the processes underlying adaptive divergence in sympatry. [ABSTRACT FROM AUTHOR]

Indolyloxazole alkaloids occur in diverse micro‐ and macroorganisms and exhibit a wide range of pharmacological activities. Despite their ubiquitous occurrence and simple structures, the biosynthetic pathway remained unknown. Here, we used transposon mutagenesis in the labradorin producer Pseudomonas entomophila to identify a cryptic biosynthetic locus encoding an N‐acyltransferase and a non‐heme diiron desaturase‐like enzyme. Heterologous expression in E. coli demonstrates that both enzymes are sufficient to produce indolyloxazoles. Probing their function in stable‐isotope feeding experiments, we provide evidence for an unusual desaturase mechanism that generates the oxazole by decarboxylative cyclization. [ABSTRACT FROM AUTHOR]

Introduction: Success rates of catheter ablation in persistent atrial fibrillation (AF) remain suboptimal. A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes. Methods: The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first‐time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI + fibrosis‐guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3–12 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90‐day postablation blanking period. Patients were followed for a period of 12–18 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint. Results and Conclusion: The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden. [ABSTRACT FROM AUTHOR]

Background: Optimal antithrombotic therapy following left atrial appendage closure (LAAC) with the Watchman occluder remains uncertain. This study retrospectively compared clinical outcomes of a 3‐month dual antiplatelet therapy (DAPT group) and a protocol of anticoagulation plus aspirin for 45 days followed by DAPT for 6 months (ACT group) after LAAC with the Watchman device. Methods: Of two Watchman registries (Coburg and Lichtenfels hospitals, Germany), 220 and 304 consecutive patients with successful LAAC were included. Patients in Coburg hospital received DAPT while they received ACT in Lichtenfels. After a 1:1 propensity score matching, 174 (DAPT) versus 174 (ACT) patients were compared by use of the primary efficacy endpoint of thromboembolic events and cardiovascular/unexplained death, the primary safety endpoint of nonprocedural related major bleeding events at follow‐up, and the combined hazard endpoint, a composite of all above‐mentioned hazards. Results: The mean age 77.5 ± 7.2 (DAPT) versus 77.3 ± 7.1 (ACT) years, CHA2DS2‐VASc score 4.6 ± 1.5 versus 4.7 ± 1.6, and HAS‐BLED score 3.3 ± 0.8 versus 3.3 ± 0.8 were similar. After 12 months, the clinical efficacy (13/174, 7.4% [DAPT] vs 11/174, 6.3% [ACT]; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.38‐1.86; P =.66) and safety (6/174, 3.4% vs 8/174, 4.5%; HR, 0.86; 95% CI, 0.29‐2.56; P =.79) as well as the combined hazard endpoint (18/174, 10.3% vs 18/174, 10.3%; HR,1.01; 95% CI, 0.53‐1.95; P =.97) were comparable. Conclusions: This study suggests comparable efficacy and safety of 3‐month DAPT versus 6 weeks ACT plus aspirin following LAAC with the Watchman. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.Methods and Results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3% [95% confidence interval (CI) 95.8-100.0] and 99.6% (95% CI 97.6-100.0), respectively. Survival rate was 86.2%. For the 12 months post- vs. pre-implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).Conclusion: Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms. [ABSTRACT FROM AUTHOR]

Introduction: The LAmbre (LifeTech Scientific, Shenzhen, China) is a novel occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation. This study compares late clinical outcomes of LAmbre and the established Amplatzer devices (Abbott, St Paul, MN). Methods: Between 2012 and 2018, 265 consecutive patients underwent LAAC with LAmbre and Amplatzer devices at a single center. After a 3:1 propensity score matching, 40 (LAmbre) vs 107 (Amplatzer) patients were compared by the primary efficacy endpoint of all‐cause stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major periprocedural complications and major bleeding events at follow‐up, and the combined hazard endpoint, a composite of all the above‐mentioned hazards. Results: The mean age 75.6 ± 8.9 (LAmbre) vs 75.5 ± 9.0 (Amplatzer) years, CHA2DS2‐VASc score 4.8 ± 1.7 vs 4.8 ± 1.7 and HAS‐BLED score 3.1 ± 0.9 vs 3.2 ± 0.8 were similar. After 3.6 ± 1.9 vs 2.5 ± 1.4 years, the clinical efficacy (12/146, 8.2% [LAmbre] vs 28/266, 10.5% [Amplatzer]; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.38‐1.40; P =.34) and safety (5/146, 3.4% vs 14/266, 5.3%; HR, 0.47; 95% CI, 0.14‐1.6; P =.22), as well as the combined hazard endpoint (15/146, 10.3% vs 36/266, 13.6%; HR, 0.67; 95% CI, 0.36‐1.25; P =.21) were comparable. Conclusion: In the presented report, in patients with nonvalvular atrial fibrillation, the LAmbre offered similar long‐term efficacy and safety in comparison to Amplatzer devices. [ABSTRACT FROM AUTHOR]

Aims: Early recurrences (ER) of atrial arrhythmias are common after catheter ablation of atrial fibrillation (AF). The significance of these ER is controversial. Based on data of continuous cardiac monitoring, we sought to investigate the characteristics of ER and their impact on late recurrences (LR) during follow‐up. Methods: One hundred twenty‐six patients with paroxysmal (49%) or persistent (51%) AF underwent an AF ablation with subsequent implantation of implantable loop recorder. Follow up was 12 months using remote monitoring. All atrial arrhythmia (AF or atrial tachycardia‐AT‐) episodes >30 seconds. within the 3‐month blanking period were considered and the AF burden evaluated every 3 months. Results: Within the 3‐months blanking period, 72 patients (57%) experienced an AF/AT recurrence. Survival free from any arrhythmia recurrence during follow‐up was 40% in patients with ER vs 69% in those without ER. AF burden during the blanking period and timing of ER correlated significantly with LR at 12 months (area under curve = 0.74, P < .0001 and.831, P < .0001). An AF burden ≥0.5% and ER after 74 days predicted LR (sensitivity 60%, specificity 84.4%; sensitivity 75.6%, specificity 90.3%). In cox regression analysis, AF burden ≥0.5% and ER after 74 days were independently associated with LR. Conclusion: Continuous cardiac monitoring after AF ablation provides important information regarding early recurrence episodes and their prognostic impact. A cut‐off of 74 days for the blanking period seems to better differentiate patients with a good or a poor long‐term outcome. An AF burden ≥0.5% during the 3 months postablation is predictive for late arrhythmia recurrences. [ABSTRACT FROM AUTHOR]

Introduction: Dual‐coil leads (DC‐leads) were the standard of choice since the first nonthoracotomy implantable cardioverter/defibrillator (ICD). We used contemporary data to determine if DC‐leads offer any advantage over single‐coil leads (SC‐leads), in terms of defibrillation efficacy, safety, clinical outcome, and complication rates. Methods and Results: In the Shockless IMPLant Evaluation study, 2500 patients received a first implanted ICD and were randomized to implantation with or without defibrillation testing. Two thousand and four hundred seventy‐five patients received SC‐coil or DC‐coil leads (SC‐leads in 1025/2475 patients; 41.4%). In patients who underwent defibrillation testing (n = 1204), patients with both lead types were equally likely to achieve an adequate defibrillation safety margin (88.8% vs 91.2%; P = 0.16). There was no overall effect of lead type on the primary study endpoint of "failed appropriate shock or arrhythmic death" (adjusted HR 1.18; 95% CI, 0.86‐1.62; P = 0.300), and on all‐cause mortality (SC‐leads: 5.34%/year; DC‐leads: 5.48%/year; adjusted HR 1.16; 95% CI, 0.94‐1.43; P = 0.168). However, among patients without prior heart failure (HF), and SC‐leads had a significantly higher risk of failed appropriate shock or arrhythmic death (adjusted HR 7.02; 95% CI, 2.41‐20.5). There were no differences in complication rates. Conclusion: In this nonrandomized evaluation, there was no overall difference in defibrillation efficacy, safety, outcome, and complication rates between SC‐leads and DC‐leads. However, DC‐leads were associated with a reduction in the composite of failed appropriate shock or arrhythmic death in the subgroup of non‐HF patients. Considering riskier future lead extraction with DC‐leads, SC‐leads appears to be preferable in the majority of patients. [ABSTRACT FROM AUTHOR]

Summary: Metschnikowia pulcherrima synthesises the pigment pulcherrimin, from cyclodileucine (cyclo(Leu‐Leu)) as a precursor, and exhibits strong antifungal activity against notorious plant pathogenic fungi. This yeast therefore has great potential for biocontrol applications against fungal diseases; particularly in the phyllosphere where this species is frequently found. To elucidate the molecular basis of the antifungal activity of M. pulcherrima, we compared a wild‐type strain with a spontaneously occurring, pigmentless, weakly antagonistic mutant derivative. Whole genome sequencing of the wild‐type and mutant strains identified a point mutation that creates a premature stop codon in the transcriptional regulator gene SNF2 in the mutant. Complementation of the mutant strain with the wild‐type SNF2 gene restored pigmentation and recovered the strong antifungal activity. Mass spectrometry (UPLC HR HESI‐MS) proved the presence of the pulcherrimin precursors cyclo(Leu‐Leu) and pulcherriminic acid and identified new precursor and degradation products of pulcherriminic acid and/or pulcherrimin. All of these compounds were identified in the wild‐type and complemented strain, but were undetectable in the pigmentless snf2 mutant strain. These results thus identify Snf2 as a regulator of antifungal activity and pulcherriminic acid biosynthesis in M. pulcherrima and provide a starting point for deciphering the molecular functions underlying the antagonistic activity of this yeast. [ABSTRACT FROM AUTHOR]

Background: An increasing number of methods are being used to map atrial fibrillation (AF), yet the sensitivity of identifying potential localized AF sources of these novel methods are unclear. Here, we report a comparison of two approaches to map AF based upon (1) electrographic flow mapping and (2) phase mapping in a multicenter registry of patients in whom ablation terminated persistent AF. Methods: Fifty‐three consecutive patients with persistent AF in whom ablation terminated AF in an international multicenter registry were enrolled. Electrographic flow mapping (EGF) and phase mapping were applied to the multipolar simultaneous electrograms recorded from a 64‐pole basket catheter in the chamber (left vs right atrium) where AF termination occurred. We analyzed if the mapping methods were able to detect localized sources at the AF termination site. We also analyzed global results of mapping AF for each method, patterns of activation of localized sources. Results: Patients were 64.3 ± 9.4 years old and 69.8% were male. EGF and phase mapping identified localized sources at AF termination sites in 81% and 83% of the patients, respectively. Methods were complementary and in only n = 2 (3.7%) neither method identified a source. Globally, EGF identified more localized sources than phase mapping (5.3 ± 2.8 vs 1.8 ± 0.5, P < 0.001), with a higher prevalence of focal (compared to rotational) activation pattern (49% vs 2%, P < 0.01). Conclusions: EGF is a novel vectorial‐based AF mapping method, which can detect sites of AF termination, agreeing with, and complementary to, an alternative AF mapping method using phase analysis. [ABSTRACT FROM AUTHOR]

Summary: Biotrophic fungal plant pathogens can balance their virulence and form intricate relationships with their hosts. Sometimes, this leads to systemic host colonization over long time scales without macroscopic symptoms. However, how plant‐pathogenic endophytes manage to establish their sustained systemic infection remains largely unknown.Here, we present a genomic and transcriptomic analysis of Thecaphora thlaspeos. This relative of the well studied grass smut Ustilago maydis is the only smut fungus adapted to Brassicaceae hosts. Its ability to overwinter with perennial hosts and its systemic plant infection including roots are unique characteristics among smut fungi.The T. thlaspeos genome was assembled to the chromosome level. It is a typical smut genome in terms of size and genome characteristics. In silico prediction of candidate effector genes revealed common smut effector proteins and unique members. For three candidates, we have functionally demonstrated effector activity. One of these, TtTue1, suggests a potential link to cold acclimation. On the plant side, we found evidence for a typical immune response as it is present in other infection systems, despite the absence of any macroscopic symptoms during infection.Our findings suggest that T. thlaspeos distinctly balances its virulence during biotrophic growth ultimately allowing for long‐lived infection of its perennial hosts. [ABSTRACT FROM AUTHOR]

Bumblebees are important pollinators for a wide range of crops and wild plants. Performance of their colonies depends on pollen and nectar as food resources, but flowering plants are scarce in modern agricultural landscapes. It is well‐known that semi‐natural habitats can enhance floral resources and bumblebee abundance, but the impact of different crop types and their heterogeneity at the landscape scale remains unclear.We tested the effect of two different crop types (oilseed rape [OSR] and maize) and of configurational (field border density) and compositional heterogeneity (crop diversity) on weight gain of buff‐tailed bumblebee colonies (Bombus terrestris) and the pollen diversity collected by them in 20 landscapes in Central Germany.We found that augmenting maize cover had a detrimental effect on pollen diversity collected by bumblebees, probably due to intensive management resulting in low plant diversity. This low pollen diversity translated into reduced colony growth, since colonies with high pollen diversity gained more weight than colonies with low pollen diversity.In contrast, OSR cover and configurational and compositional heterogeneity did neither affect colony growth nor pollen diversity. However, for OSR, the timing of the flowering period was important. When OSR fields had a high flower cover at the end of the OSR blooming period, colonies showed increased growth rates.Synthesis and applications. Our results complement previous laboratory studies by showing that high pollen diversity leads to better colony performance under field conditions. Therefore, the maintenance of floral diversity in agricultural landscapes is crucial to ensure that bumblebees can fulfil their nutritional needs. However, the heterogeneity of crops, at least under the currently very low levels of crop rotation, does not contribute to this aim. In contrast, crop identity and timing of mass‐flowering crops turned out to be important factors, as maize reduced pollen resources, while late blooming oilseed rape (OSR) was beneficial to bumblebee colonies. Hence, maize cover per landscape should be reduced and strategies to enhance landscape wide flower diversity, especially towards and after the end of oilseed rape bloom, should be promoted to support bumblebee colonies that provide important pollination services. Our results complement previous laboratory studies by showing that high pollen diversity leads to better colony performance under field conditions. Therefore, the maintenance of floral diversity in agricultural landscapes is crucial to ensure that bumblebees can fulfil their nutritional needs. However, the heterogeneity of crops, at least under the currently very low levels of crop rotation, does not contribute to this aim. In contrast, crop identity and timing of mass‐flowering crops turned out to be important factors, as maize reduced pollen resources, while late blooming oilseed rape (OSR) was beneficial to bumblebee colonies. Hence, maize cover per landscape should be reduced and strategies to enhance landscape wide flower diversity, especially towards and after the end of oilseed rape bloom, should be promoted to support bumblebee colonies that provide important pollination services. [ABSTRACT FROM AUTHOR]

Great interest in the comparative physiology of hearts and their functions in Animalia has emerged with classic papers on Limulus polyphemus and mollusks. The recurrent cardiac activity—heart rate—is the most important physiological parameter and when present the kardia (Greek) is vital to the development of entire organs of the organisms in the animal kingdom. Extensive studies devoted to the regulation of cardiac rhythm in invertebrates have revealed that the basics of heart physiology are comparable to mammals. The hearts of invertebrates also beat spontaneously and are supplied with regulatory nerves: either excitatory or inhibitory or both. The distinct nerves and the source of excitation/inhibition at the level of single neurons are described for many invertebrate genera. The vertebrates and a majority of invertebrates have myogenic hearts, whereas the horseshoe crab L. polyphemus and a few other animals have a neurogenic cardiac rhythm. Nevertheless, the myogenic nature of heartbeat is precursor, because the contraction of native and stem‐cell‐derived cardiomyocytes does occur in the absence of any neural elements. Even in L. polyphemus, the heart rhythm is myogenic at embryonic stages. Xiphosura (from Greek—sword tail, Мечехвост—Russian, Schwertschwanz—German) are important for the elucidation of the evolution of behavior and physiology, especially that of cor. They contain unknown structures within the myocardium. Note one of the evolutionarily conserved aspects of life in behaving − mating (1 female ♀ and six males ♂) L. polyphemus. A complete tetanus could be defined as a similar event to the systolic arrest in Mammalia. There is a transition from a myogenic cardiac rhythm to a neurogenic one in L. polyphemus. [ABSTRACT FROM AUTHOR]

Abstract: The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq‐related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC‐1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time. [ABSTRACT FROM AUTHOR]

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The plant-specific PALE CRESS (PAC) protein has previously been shown to be essential for photoautotrophic growth. Here we further investigated the molecular function of the PAC protein. PAC localizes to plastid nucleoids and forms large proteinaceous and RNA-containing megadalton complexes. It co-immunoprecipitates with a specific subset of chloroplast RNAs including psbK-psbI, ndhF, ndhD, and 23S ribosomal RNA (rRNA), as demonstrated by RNA immunoprecipitation in combination with high throughput RNA sequencing (RIP-seq) analyses. Furthermore, it co-migrates with premature 50S ribosomal particles and specifically binds to 23S rRNA in vitro. This coincides with severely reduced levels of 23S rRNA in pac leading to translational deficiencies and related alterations of plastid transcript patterns and abundance similar to plants treated with the translation inhibitor lincomycin. Thus, we conclude that deficiency in plastid ribosomes accounts for the pac phenotype. Moreover, the absence or reduction of PAC levels in the corresponding mutants induces structural changes of the 23S rRNA, as demonstrated by in vivo RNA structure probing. Our results indicate that PAC binds to the 23S rRNA to promote the biogenesis of the 50S subunit. [ABSTRACT FROM AUTHOR]

Left Atrial Appendage Closure With the New Occlutech® Device Aims Percutaneous left atrial appendage closure (LAAC) is a valuable treatment option for stroke prevention in patients with atrial fibrillation and a HAS-BLED-Score ≥3. Determinants of procedural safety events and neurological outcome of the patients with the Occlutech device (OD) are not established yet. Methods and Results Between 2012 and 2016, 30 patients underwent LAAC using the OD. This is a prospective study. Neurological examination and transesophageal echocardiography was performed directly before and after the procedure and after 1, 3, and 12 months. The OC was successfully implanted in 28 of the 30 enrolled patients (93%). Two patients presented a hemodynamic relevant pericardial effusion. A leak <3 mm could be documented direct after implantation in 4 patients. After 3 months, there were only 2/4 patients with persistent LAA leakage with a maximum leakage of <3 mm. The correct position of the device was confirmed in 27/28 patients during 3-month follow-up. In 2 patients, there was a thrombus at the OC. In 12 patients, a transoesophageal echocardiography was performed after 12 months. All patients (12/12) showed a correct placement of the device. None of the patients developed a clinically apparent stroke or died during follow-up. Conclusion In this uncontrolled, nonrandomized study, acute and 3-month follow-up success of LAAC using OD was high. No patient showed significant neurological deficits. [ABSTRACT FROM AUTHOR]

Age-Related Complication Rates in AF Ablation Introduction Despite a rising demand for catheter ablation (CA) of atrial fibrillation (AF) in an elderly population, complication and success rates are not fully elucidated. We sought to compare complication rates of CA of AF in patients ≥75 versus <75 years of age. Methods and Results Patients with symptomatic, drug-refractory AF were prospectively enrolled from January 2007 to 2010 in this multicenter study. A total of 4,449 patients, group 1 ≥75 years and group 2 <75 years (n = 227, age 77.3 ± 2.2 vs. 59.7 ± 9.8 years, 52.0% vs. n = 4,222, 68.9% male, CHA2DS2-VASc-Score 3.7 ± 1.0 vs. 1.7 ± 1.2; P < 0.001, respectively), with paroxysmal AF (59.9% in group 1 vs. 63.3% in group 2, P = 0.30), and persistent AF (34.8% in group 1 vs. 29.4% in group 2, P = 0.082) underwent CA of AF. A centralized follow-up was obtained in 4,347 patients by the Institute for Myocardial Infarction Research (IHF, Ludwigshafen). There was a significant difference between periprocedural stroke rates in the elderly versus the younger cohort (1.3% vs. 0.1%, P < 0.01). In-hospital severe nonfatal complications did not differ significantly between the groups (4.4% vs. 2.7%, P = 0.14). Other procedure-related, in-hospital complications were not significantly different. After a mean follow-up of 472 ± 99 days (group 1) and 477 ± 94 days (group 2), no differences were found in complication rates. Conclusion CA of AF in patients ≥75 years is associated with higher in-hospital stroke rates. In a 1-year follow-up, complication rates do not differ between the groups. [ABSTRACT FROM AUTHOR]

DETECT AF Study Results Introduction Reliable detection and monitoring of atrial fibrillation (AF) is essential for accurate clinical decision making, which can now be done continuously with the introduction of implantable cardiac monitors (ICM) The DETECT AF study evaluated the performance of the Confirm DM2102 ICM (St. Jude Medical, St. Paul, MN, USA) to accurately detect and monitor AF. Methods Ninety patients previously implanted with the ICM and with either suspected or known paroxysmal AF were enrolled at 12 centers in Germany and The Netherlands. At least 2 weeks after ICM implant, patients wore a Holter monitor for 4 days, while the ICM monitored for AF episodes lasting at least 2 minutes. Holter monitor data was analyzed by a blinded, independent core laboratory and compared to the ICM AF detections. Patient and episode sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive (NPV) were calculated using standard analysis and a generalized estimation equation method where appropriate. Results A total of 79/90 subjects (61% male, 65.7 ± 9.6 years old) were included in the analysis, totaling 6,894 hours of Holter monitoring. Using a per patient analysis SE was 100%, PPV was 64.0%, SP was 85.7%, and NPV was 100%. Using a per episode analysis, SE was 94.0% and PPV was 64.0%. With an AF duration analysis, the SE was 83.9%, PPV was 97.3%, SP was 99.4% with an NPV of 98.5%. Conclusion The SJM Confirm DM2102 can accurately and repeatedly detect paroxysmal AF episodes of at least 2 minutes in length. [ABSTRACT FROM AUTHOR]

Aims: The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs. 'off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power.Conclusion: The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014. [ABSTRACT FROM AUTHOR]

ICD Lead Position and Outcome Introduction We aim to compare the acute and long-term success of defibrillation between non-apical and apical ICD lead position. Methods and Results The position of the ventricular lead was recorded by the implanting physician for 2,475 of 2,500 subjects in the Shockless IMPLant Evaluation (SIMPLE) trial, and subjects were grouped accordingly as non-apical or apical. The success of intra-operative defibrillation testing and of subsequent clinical shocks were compared. Propensity scoring was used to adjust for the impact of differences in baseline variables between these groups. There were 541 leads that were implanted at a non-apical position (21.9%). Patients implanted with a non-apical lead had a higher rate of secondary prevention indication. Non-apical location resulted in a lower mean R-wave amplitude (14.0 vs. 15.2, P < 0.001), lower mean pacing impedance (662 ohm vs. 728 ohm, P < 0.001), and higher mean pacing threshold (0.70 V vs. 0.66 V, P = 0.01). Single-coil leads and cardiac resynchronization devices were used more often in non-apical implants. The success of intra-operative defibrillation was similar between propensity score matched groups (89%). Over a mean follow-up of 3 years, there were no significant differences in the yearly rates of appropriate shock (5.5% vs. 5.4%, P = 0.98), failed appropriate first shock (0.9% vs. 1.0%, P = 0.66), or the composite of failed shock or arrhythmic death (2.8% vs. 2.3% P = 0.35) according to lead location. Conclusion We did not detect any reduction in the ICD efficacy at the time of implant or during follow-up in patients receiving a non-apical RV lead. [ABSTRACT FROM AUTHOR]

While magnetosome biosynthesis within the magnetotactic P roteobacteria is increasingly well understood, much less is known about the genetic control within deep-branching phyla, which have a unique ultrastructure and biosynthesize up to several hundreds of bullet-shaped magnetite magnetosomes arranged in multiple bundles of chains, but have no cultured representatives. Recent metagenomic analysis identified magnetosome genes in the genus ' C andidatus Magnetobacterium' homologous to those in P roteobacteria. However, metagenomic analysis has been limited to highly abundant members of the community, and therefore only little is known about the magnetosome biosynthesis, ecophysiology and metabolic capacity in deep-branching MTB. Here we report the analysis of single-cell derived draft genomes of three deep-branching uncultivated MTB. Single-cell sorting followed by whole genome amplification generated draft genomes of C andidatus Magnetobacterium bavaricum and C andidatus Magnetoovum chiemensis CS-04 of the N itrospirae phylum. Furthermore, we present the first, nearly complete draft genome of a magnetotactic representative from the candidate phylum Omnitrophica, tentatively named C andidatus Omnitrophus magneticus SKK-01. Besides key metabolic features consistent with a common chemolithoautotrophic lifestyle, we identified numerous, partly novel genes most likely involved in magnetosome biosynthesis of bullet-shaped magnetosomes and their arrangement in multiple bundles of chains. [ABSTRACT FROM AUTHOR]

Es wird die bislang größte zusammenhängende bakterielle nicht ‐ ribosomale Peptidsynthetase (NRPS) beschrieben, die aus 15 konsekutiven Modulen besteht und aus einem einzigen voll funktionalen Gen des entomopathogenen Bakteriums Photorhabdus luminescens hervorgeht. Die Identifikation ihres kryptischen Biosyntheseprodukts wurde mithilfe einer Kombination aus Genomanalyse, Promotoraustausch, Isotopenmarkierung und Totalsynthese einer fokussierten Sammlung von Peptidkandidaten erreicht. Obwohl zur wachsenden Klasse der D ‐ /L ‐ Peptid ‐ Naturstoffe zählend, wies der produzierte Metabolit Kolossin A keine nennenswerte antibakterielle Aktivität auf und ist möglicherweise an einer Interspeziesinteraktion beteiligt. Ein Stereoisomer des ungewöhnlichen Naturstoffs zeigte hohe Aktivität gegen Trypanosoma brucei rhodesiense, einen hartnäckigen Parasiten, der die tödliche afrikanische Schlafkrankheit verursacht. Ein schlafender Riese: Im entomopathogenen Bakterium Photorhabdus luminescens wurde eine einzelne nicht ‐ ribosomale Peptidsynthetase von 1.8 MDa gefunden und ihre Bildung gezielt aktiviert. Das 15 ‐ mere D ‐ /L ‐ Peptidprodukt dieser Biosynthese wurde durch Kombination von Genomanalyse des stillen Genclusters, Molekularbiologie, LC ‐ MS und Totalsynthese charakterisiert. Ein Stereoisomer von Kolossin A ist aktiv gegen den Erreger der afrikanischen Schlafkrankheit. [ABSTRACT FROM AUTHOR]

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D-/ L-peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness. [ABSTRACT FROM AUTHOR]

Background Cardiac resynchronization therapy (CRT) relies on sufficient left ventricular (LV) pacing with safety margin to phrenic nerve stimulation (PNS). Previous studies introduced LV vector reprogramming in bipolar coronary sinus leads to optimize LV pacing and avoid PNS. We investigated the efficacy and reliability of quadripolar leads in CRT. Methods The EffaceQ study enrolled 344 patients with de novo CRT implantation with a quadripolar LV lead in an observational, prospective multicenter study. The study was powered to demonstrate that in at least 90% of patients with an implanted quadripolar LV lead, a viable LV pacing configuration (LVPC) is available (primary end point: LV pacing threshold ≤2.5 V/0.5 ms, sufficient PNS margin). Results Quadripolar leads were successfully implanted in 96% of patients. A total of 278 of 299 (93.0%) patients with complete data met the criteria for viable LVPC. With the use of traditional LVPCs, a viable LVPC would have been available (268 of 299 patients; P = 0.002) in significantly fewer patients (89.6%). In any LVPC, PNS was inducible in 65.0% of patients and 22.6% of patients reported PNS during ambulatory 3-month follow-up. LVPC reprogramming was performed in 49.8% of patients. PNS inducibility decreased from distal to proximal electrodes, whereas LV pacing thresholds increased from distal to proximal. At prehospital discharge, 5.9 ± 2.8 viable LVPCs were observed, stable during follow-up. The quadripolar electrode offered significantly more LVPC for LV optimization and PNS avoidance. Conclusion Quadripolar LV leads yield high numbers of patients with viable LVPCs and alternatives for noninvasive repositioning of LV pacing. [ABSTRACT FROM AUTHOR]