Catheter ablation of fractionated electrograms for atrial fibrillation: does it improve outcomes and can it be refined based on electrogram morphology or knowledge of the remodelling process?.

PhDCatheter ablation complex or fractionated atrial electrograms (CFAE) may improve outcomes for persistent AF. However, it is unclear whether CFAE are important in maintaining AF or whether targeting of CFAE can be refined based on electrogram morphology or knowledge of the remodelling process. A detailed classification of CFAE was described. Assessment of 100 CFAE by visual inspection in real time correlated well with detailed offline measurement. Targeting of different CFAE morphologies in 20 patients with persistent AF caused cycle length prolongation only with ablation of certain CFAE morphologies. Therefore, targeting CFAE is not simply atrial de-bulking, certain CFAE morphologies are more important for maintaining AF. A computer model was established to simulate LA wall stress using a 3D reconstruction of the chamber from CT imaging. Electrophysiologic data was acquired in 19 patients in persistent AF and compared to simulated wall stress data. Peaks in wall stress were associated with areas of low voltage suggestive of focal remodelling. CFAE were not associated with peaks in wall stress or areas of remodelling. Wall stress did not determine whether ablation of CFAE caused cycle length prolongation. Long term outcome of catheter ablation for AF was good with little late recurrence. Outcome for persistent AF was improved by targeting CFAE in addition to pulmonary vein isolation and may reduce late recurrenceBritish Heart Foundatio

Measurements of shipping, fin whales, earthquakes and other soundscape components at the Lofoten-Vesterålen Observatory, Norway (2018-2019)

Underwater soundscapes are complex as they are a combination of several components with overlapping acoustic frequencies and different timescales, from individual durations to seasonality and long-term trends. Sounds below 100 Hz are of particular interest to compare human impacts with natural processes and animal vocalisations, but understanding is often limited to specific signals on their own, not their combination. We have processed over two years (2018 and 2019) of measurements from the Lofoten-Vesteralen cabled ocean observatory, located 15 km offshore northern Norway, at a depth of 255 m. Earlier analyses (Garibbo et al., 2020,1 Garibbo et al., 20212) identified the different contributions of weather, shipping and earthquakes in data collected in 2018, using deep learning to automatically detect common 20 Hz fin whale calls. The results of the deep learning approach are compared to a new, improved shipping detector, based on traditional spectral analyses, showing the complementarity of each approach. By extending these analyses using data from 2019, we can quantify the standard soundscape components based on origins, frequency ranges and seasonality, and assess their variability over time. These extensive results provide a useful baseline for further studies of other low-frequency environments around the world.</p

Understanding Accretion Outbursts in Massive Protostars through Maser Imaging

The bright maser emission produced by several molecular species at centimeter to long millimeter wavelengths provides an essential tool for understanding the process of massive star formation. Unimpeded by the high dust optical depths that affect shorter wavelength observations, the high brightness temperature of these emission lines offers a way to resolve accretion and outflow motions down to scales below $\sim$1 au in deeply embedded Galactic star-forming regions at kiloparsec distances. The recent identification of extraordinary accretion outbursts in two high-mass protostars, both of which were heralded by maser flares, has rapidly impacted the traditional view of massive protostellar evolution, leading to new hydrodynamic simulations that can produce such episodic outbursts. In order to understand how these massive protostars evolve in response to such events, larger, more sensitive ground-based centimeter wavelength interferometers are needed that can simultaneously image multiple maser species in the molecular gas along with faint continuum from the central ionized gas. Fiducial observations of a large sample of massive protostars will be essential in order to pinpoint the progenitors of future accretion outbursts, and to quantify the outburst-induced changes in their protostellar photospheres and outflow and accretion structures. Knowledge gained from these studies will have broader impact on the general topic of accretion onto massive objects.Comment: Science white paper submitted to the Astro2020 Decadal Survey. arXiv admin note: substantial text overlap with arXiv:1806.0698

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms

Right ventricular function is a predictor for sustained ventricular tachycardia requiring anti-tachycardic pacing in arrhythmogenic ventricular cardiomyopathy: insight into transvenous vs. subcutaneous implantable cardioverter defibrillator insertion

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients develop ventricular arrhythmias (VAs) responsive to anti-tachycardia pacing (ATP). However, VA episodes have not been characterized in accordance with the device therapy, and with the emergence of the subcutaneous implantable cardioverter defibrillator (S-ICD), the appropriate device prescription in ARVC remains unclear. Study aim was to characterize VA events in ARVC patients during follow-up in accordance with device therapy and elicit if certain parameters are predictive of specific VA events. METHODS AND RESULTS: This was a retrospective single-centre study utilizing prospectively collated registry data of ARVC patients with ICDs. Forty-six patients were included [54.0 ± 12.1 years old and 20 (43.5%) secondary prevention devices]. During a follow-up of 12.1 ± 6.9 years, 31 (67.4%) patients had VA events [n = 2, 6.5% ventricular fibrillation (VF), n = 14], 45.2% VT falling in VF zone resulting in ICD shock(s), n = 10, 32.3% VT resulting in ATP, and n = 5, 16.1% patients had both VT resulting in ATP and ICD shock(s). Lead failure rates were high (11/46, 23.9%). ATP was successful in 34.5% of patients. Severely impaired right ventricular (RV) function was an independent predictor of VT resulting in ATP (hazard ratio 16.80, 95% confidence interval 3.74–75.2; P < 0.001) with a high predictive accuracy (area under the curve 0.88, 95%CI 0.76–1.00; P < 0.001). CONCLUSION: VA event rates are high in ARVC patients with a majority having VT falling in the VF zone resulting in ICD shock(s). S-ICDs could be of benefit in most patients with ARVC with the absence of severely impaired RV function which has the potential to avoid consequences of the high burden of lead failure

Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.

Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP-/- and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the betaARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy

Responses of Sunda clouded leopard population density to anthropogenic disturbance and refining estimates of their conservation status in Sabah

Extensive areas of tropical forests have been, and continue to be, disturbed as a result of selective timber extraction. Although such anthropogenic disturbance typically results in the loss of biodiversity, many species persist, and their conservation in production landscapes could be enhanced by a greater understanding of how biodiversity responds to forest management practices. We conducted intensive camera-trap surveys of eight protected forest areas in Sabah, Malaysian Borneo, and developed estimates of Sunda clouded leopard Neofelis diardi population density from spatially explicit capture–recapture analyses of detection data to investigate how the species’ abundance varies across the landscape and in response to anthropogenic disturbance. Estimates of population density from six forest areas were 1.39–3.10 individuals per 100 km2. Our study provides the first evidence that the population density of the Sunda clouded leopard is negatively affected by hunting pressure and forest fragmentation, and that among selectively logged forests, time since logging is positively associated with abundance. We argue that these negative anthropogenic impacts could be mitigated with improved logging practices, such as reducing the access of poachers by effective gating and destruction of road access points, and by the deployment of anti-poaching patrols. By calculating a weighted mean population density estimate from estimates developed here and from the literature, and by extrapolating this value to an estimate of current available habitat, we estimate there are 754 (95% posterior interval 325–1,337) Sunda clouded leopards in Sabah

Spatio-temporal ecology of sympatric felids on Borneo. Evidence for resource partitioning?

Niche differentiation, the partitioning of resources along one or more axes of a species’ niche hyper-volume, is widely recognised as an important mechanism for sympatric species to reduce interspecific competition and predation risk, and thus facilitate co-existence. Resource partitioning may be facilitated by behavioural differentiation along three main niche dimensions: habitat, food and time. In this study, we investigate the extent to which these mechanisms can explain the coexistence of an assemblage of five sympatric felids in Borneo. Using multi-scale logistic regression, we show that Bornean felids exhibit differences in both their broad and fine-scale habitat use. We calculate temporal activity patterns and overlap between these species, and present evidence for temporal separation within this felid guild. Lastly, we conducted an all-subsets logistic regression to predict the occurrence of each felid species as a function of the co-occurrence of a large number of other species and showed that Bornean felids co-occurred with a range of other species, some of which could be candidate prey. Our study reveals apparent resource partitioning within the Bornean felid assemblage, operating along all three niche dimension axes. These results provide new insights into the ecology of these species and the broader community in which they live and also provide important information for conservation planning for this guild of predators