Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Humangenetische Beratung in Deutschland: Entwicklung der Inanspruchnahme

Background!#!With the Act on Genetic Testing (GenDG), the German legislator has issued far-reaching regulations for human genetic services, including genetic counseling. This paper presents data on the use of human genetic counseling in the years before and after the entry into force of GenDG in order to provide an informed assessment of the possible effects of the law.!##!Materials and methods!#!Over a period of 13 years (2005 to 2017), the human genetic counseling services provided within the framework of the statutory health insurance and billable by EBM via the Kassenärztliche associations were recorded via a database query at the Central Institute of the National Association of Statutory Health Insurance Physicians (ZI-KBV) and via individual Kassenärztliche Vereinigungen Deutschlands. For the discussion of the observable development of using genetic counseling and possible future development, additional data on the referral behavior, the waiting times, processing time, and reasons for consultations were extracted from the GenBIn database.!##!Results and discussion!#!Demand for genetic counseling has steadily increased at an average rate of approximately 6% per year since 2009. This increase started well before the enactment of the GenDG and may be attributed to a multiplicity of factors. Change in demand for genetic counseling is characterized by increasing self-referrals and by increasing referrals by specialists other than obstetricians/gynecologists. Waiting times between 2011 and 2016/2017 have increased. While demand has been growing, the number of key service providers, the contracted medical specialists in human genetics, has remained almost constant. It is foreseeable that capacity limits will be reached if both trends continue

State changes: insights from the U.S. Long Term Ecological Research Network

Abstract Understanding the complex and unpredictable ways ecosystems are changing and predicting the state of ecosystems and the services they will provide in the future requires coordinated, long‐term research. This paper is a product of a U.S. National Science Foundation funded Long Term Ecological Research (LTER) network synthesis effort that addressed anticipated changes in future populations and communities. Each LTER site described what their site would look like in 50 or 100 yr based on long‐term patterns and responses to global change drivers in each ecosystem. Common themes emerged and predictions were grouped into state change, connectivity, resilience, time lags, and cascading effects. Here, we report on the “state change” theme, which includes examples from the Georgia Coastal (coastal marsh), Konza Prairie (mesic grassland), Luquillo (tropical forest), Sevilleta (arid grassland), and Virginia Coastal (coastal grassland) sites. Ecological thresholds (the point at which small changes in an environmental driver can produce an abrupt and persistent state change in an ecosystem quality, property, or phenomenon) were most commonly predicted. For example, in coastal ecosystems, sea‐level rise and climate change could convert salt marsh to mangroves and coastal barrier dunes to shrub thicket. Reduced fire frequency has converted grassland to shrubland in mesic prairie, whereas overgrazing combined with drought drive shrub encroachment in arid grasslands. Lastly, tropical cloud forests are susceptible to climate‐induced changes in cloud base altitude leading to shifts in species distributions. Overall, these examples reveal that state change is a likely outcome of global environmental change across a diverse range of ecosystems and highlight the need for long‐term studies to sort out the causes and consequences of state change. The diversity of sites within the LTER network facilitates the emergence of overarching concepts about state changes as an important driver of ecosystem structure, function, services, and futures