Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Drift simulation of MH370 debris using superensemble techniques

On 7 March 2014 (UTC), Malaysia Airlines flight 370 vanished without a trace. The aircraft is believed to have crashed in the southern Indian Ocean, but despite extensive search operations the location of the wreckage is still unknown. The first tangible evidence of the accident was discovered almost 17 months after the disappearance. On 29 July 2015, a small piece of the right wing of the aircraft was found washed up on the island of Réunion, approximately 4000 km from the assumed crash site. Since then a number of other parts have been found in Mozambique, South Africa and on Rodrigues Island. This paper presents a numerical simulation using high-resolution oceanographic and meteorological data to predict the movement of floating debris from the accident. Multiple model realisations are used with different starting locations and wind drag parameters. The model realisations are combined into a superensemble, adjusting the model weights to best represent the discovered debris. The superensemble is then used to predict the distribution of marine debris at various moments in time. This approach can be easily generalised to other drift simulations where observations are available to constrain unknown input parameters. The distribution at the time of the accident shows that the discovered debris most likely originated from the wide search area between 28 and 35° S. This partially overlaps with the current underwater search area, but extends further towards the north. Results at later times show that the most probable locations to discover washed-up debris are along the African east coast, especially in the area around Madagascar. The debris remaining at sea in 2016 is spread out over a wide area and its distribution changes only slowly

The transverse-axial tubular system of cardiomyocytes

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