Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of... Show moreCardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task. In particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and co-morbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational 'valley of death', which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models cannot provide a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on a organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and improved current animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction and refinement (3R) as a guiding concept. Show less
Morganti, R.; Oosterloo, T.A.; Brienza, M.; Jurlin, N.; Prandoni, I.; Orru, E.; ... ; Ziemke, J. 2021
Super massive black holes at the centres of galaxies can cycle through periods of activity and quiescence. Characterising the duty cycle of active galactic nuclei (AGN) is crucial for understanding... Show moreSuper massive black holes at the centres of galaxies can cycle through periods of activity and quiescence. Characterising the duty cycle of active galactic nuclei (AGN) is crucial for understanding the impact of the energy they release on the host galaxy. For radio AGN, this can be done by identifying dying (remnant) and restarted radio galaxies from their radio spectral properties. Using the combination of the images at 1400 MHz produced by Apertif, the new phased-array feed receiver installed on the Westerbork Synthesis Radio Telescope, and images at 150 MHz provided by LOFAR, we have derived resolved spectral index images (at a resolution of similar to 15 arcsec) for all the sources within an approximately 6 deg(2) area of the Lockman Hole region. In this way, we were able to select 15 extended radio sources with emission (partly or entirely) characterised by extremely steep spectral indices (steeper than 1.2). These objects represent cases of radio sources in the remnant or the restarted phases of their life cycle. Our findings confirm that these objects are not as rare as previously thought, suggesting a relatively fast cycle. They also show a variety of properties that can be relevant for modelling the evolution of radio galaxies. For example, the restarted activity can occur while the remnant structure from a previous phase of activity is still visible. This provides constraints on the duration of the "off" (dying) phase. In extended remnants with ultra-steep spectra at low frequencies, the activity likely stopped a few hundred megayears ago, and they correspond to the older tail of the age distribution of radio galaxies, in agreement with the results of simulations of radio source evolution. We find remnant radio sources with a variety of structures (from double-lobed to amorphous), possibly suggesting different types of progenitors. The present work sets the stage for exploiting the powerful tool of low-frequency spectral index studies of extended sources by taking advantage of the large areas common to the LOFAR and the Apertif surveys. Show less
