Complex patterns of spontaneous initiations and terminations of reentrant circulation in a loop of cardiac tissue

A two-component model is developed that consists of a discrete loop of cardiac cells that circulates action potentials together with a cardiac pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and their interactions with the pacer are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability of reentrant circulation (T-bistability) and in some cases, also phase-resetting interactions with the pacer.Comment: 27 pages, 10 figures, 61 references; A version of this paper (same results) is to appear in the Journal of Theoretical Biology; arXiv V2 adds helpful commments to facilitate reading and corrects minor errors in presentatio

The Planetary Nebula Luminosity Function at the Dawn of Gaia

The [O III] 5007 Planetary Nebula Luminosity Function (PNLF) is an excellent extragalactic standard candle. In theory, the PNLF method should not work at all, since the luminosities of the brightest planetary nebulae (PNe) should be highly sensitive to the age of their host stellar population. Yet the method appears robust, as it consistently produces < 10% distances to galaxies of all Hubble types, from the earliest ellipticals to the latest-type spirals and irregulars. It is therefore uniquely suited for cross-checking the results of other techniques and finding small offsets between the Population I and Population II distance ladders. We review the calibration of the method and show that the zero points provided by Cepheids and the Tip of the Red Giant Branch are in excellent agreement. We then compare the results of the PNLF with those from Surface Brightness Fluctuation measurements, and show that, although both techniques agree in a relative sense, the latter method yields distances that are ~15% larger than those from the PNLF. We trace this discrepancy back to the calibration galaxies and argue that, due to a small systematic error associated with internal reddening, the true distance scale likely falls between the extremes of the two methods. We also demonstrate how PNLF measurements in the early-type galaxies that have hosted Type Ia supernovae can help calibrate the SN Ia maximum magnitude-rate of decline relation. Finally, we discuss how the results from space missions such as Kepler and Gaia can help our understanding of the PNLF phenomenon and improve our knowledge of the physics of local planetary nebulae.Comment: 12 pages, invited review at the conference "The Fundamental Cosmic Distance Scale: State of the Art and Gaia Perspective", to appear in Astrophysics and Space Scienc

Six pelagic seabird species of the North Atlantic engage in a fly-and-forage strategy during their migratory movements

Bird migration is commonly defined as a seasonal movement between breeding and non-breeding grounds. It generally involves relatively straight and directed large-scale movements, with a latitudinal change, and specific daily activity patterns comprising less or no foraging and more traveling time. Our main objective was to describe how this general definition applies to seabirds. We investigated migration characteristics of 6 pelagic seabird species (little auk Alle alle, Atlantic puffin Fratercula arctica, common guillemot Uria aalge, Brünnich’s guillemot U. lomvia, black-legged kittiwake Rissa tridactyla and northern fulmars Fulmarus glacialis). We analysed an extensive geolocator positional and saltwater immersion dataset from 29 colonies in the North-East Atlantic and across several years (2008-2019). We used a novel method to identify active migration periods based on segmentation of time series of track characteristics (latitude, longitude, net-squared displacement). Additionally, we used the saltwater immersion data of geolocators to infer bird activity. We found that the 6 species had, on average, 3 to 4 migration periods and 2 to 3 distinct stationary areas during the non-breeding season. On average, seabirds spent the winter at lower latitudes than their breeding colonies and followed specific migration routes rather than non-directionally dispersing from their colonies. Differences in daily activity patterns were small between migratory and stationary periods, suggesting that all species continued to forage and rest while migrating, engaging in a ‘fly-and-forage’ migratory strategy. We thereby demonstrate the importance of habitats visited during seabird migrations as those that are not just flown over, but which may be important for re-fuelling.publishedVersio

The methodological quality is insufficient in clinical practice guidelines in the context of COVID-19 : systematic review

Objectives The number of published clinical practice guidelines related to COVID-19 has rapidly increased. This study explored if basic methodological standards of guideline development have been met in the published clinical practice guidelines related to COVID-19. Study Design and Setting Rapid systematic review from February 1 until April 27, 2020 using MEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search, including all types of healthcare workers providing any kind of healthcare to any patient population in any setting. Results There were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality). The majority (156; 83%) was solely built on an informal expert consensus. A process for regular updates was described in 27 guidelines (14%). Patients were included in the development of only one guideline. Conclusion Despite clear scope, most publications fell short of basic methodological standards of guideline development. Clinicians should use guidelines that include up-to-date information, were informed by stakeholder involvement, and employed rigorous methodologies

Development and potential role of type-2 sodium-glucose transporter inhibitors for management of type 2 diabetes

There is a recognized need for new treatment options for type 2 diabetes mellitus (T2DM). Recovery of glucose from the glomerular filtrate represents an important mechanism in maintaining glucose homeostasis and represents a novel target for the management of T2DM. Recovery of glucose from the glomerular filtrate is executed principally by the type 2 sodium-glucose cotransporter (SGLT2). Inhibition of SGLT2 promotes glucose excretion and normalizes glycemia in animal models. First reports of specifically designed SGLT2 inhibitors began to appear in the second half of the 1990s. Several candidate SGLT2 inhibitors are currently under development, with four in the later stages of clinical testing. The safety profile of SGLT2 inhibitors is expected to be good, as their target is a highly specific membrane transporter expressed almost exclusively within the renal tubules. One safety concern is that of glycosuria, which could predispose patients to increased urinary tract infections. So far the reported safety profile of SGLT2 inhibitors in clinical studies appears to confirm that the class is well tolerated. Where SGLT2 inhibitors will fit in the current cascade of treatments for T2DM has yet to be established. The expected favorable safety profile and insulin-independent mechanism of action appear to support their use in combination with other antidiabetic drugs. Promotion of glucose excretion introduces the opportunity to clear calories (80–90 g [300–400 calories] of glucose per day) in patients that are generally overweight, and is expected to work synergistically with weight reduction programs. Experience will most likely lead to better understanding of which patients are likely to respond best to SGLT2 inhibitors, and under what circumstances