Legal and ethical framework for global health information and biospecimen exchange - an international perspective.

BACKGROUND: The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. MAIN TEXT: Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. CONCLUSION: With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.

The role of life experience in affecting persistence: A comparative study between free-ranging dogs, pet dogs and captive pack dogs.

Persistence in object manipulation has been consistently associated with problem-solving success and it is known to be affected, at the individual level, by life experience. Differences in life experiences are particularly poorly studied in the problem-solving context and mainly refer to the comparison between wild and captive animals. Dogs represent interesting study subjects, since dog populations differ widely in their life experiences. In this comparative study we investigated subjects' persistence when presenting a novel object containing food that could not be accessed (impossible task) to three dog populations with very diverse life experiences: free-ranging village dogs (in Morocco), pet dogs (in Vienna) and captive pack living dogs (Wolf Science Center-WSC). We found that pet dogs and captive dogs (WSC) were more manipulative and persistent than free-ranging dogs. The low persistence of free ranging-dogs is unlikely the effect of a lack of exposure to objects, since they are confronted with many human' artefacts in their environment daily. Instead, we suggest that the higher persistence of captive dogs and pet dogs in comparison to free-ranging dogs might be due to their increased experience of human-mediated object interaction. This provides subjects with a socially guided experience in manipulating and interacting with objects increasing their motivation to engage in such tasks.

Differences in persistence between dogs and wolves in an unsolvable task in the absence of humans.

Despite being closely related, dogs perform worse than wolves in independent problem-solving tasks. These differences in problem-solving performance have been attributed to dogs' greater reliance on humans, who are usually present when problem-solving tasks are presented. However, more fundamental motivational factors or behavioural traits such as persistence, motor diversity and neophobia may also be responsible for differences in task performance. Hence, to better understand what drives the differences between dogs' and wolves' problem-solving performance, it is essential to test them in the absence of humans. Here, we tested equally raised and kept dogs and wolves with two unsolvable tasks, a commonly used paradigm to study problem-solving behaviour in these species. Differently from previous studies, we ensured no humans were present in the testing situation. We also ensured that the task was unsolvable from the start, which eliminated the possibility that specific manipulative behaviours were reinforced. This allowed us to measure both persistence and motor diversity more accurately. In line with previous studies, we found wolves to be more persistent than dogs. We also found motor diversity to be linked to persistence and persistence to be linked to contact latency. Finally, subjects were consistent in their performance between the two tasks. These results suggest that fundamental differences in motivation to interact with objects drive the differences in the performance of dogs and wolves in problem-solving tasks. Since correlates of problem-solving success, that is persistence, neophobia, and motor diversity are influenced by a species' ecology, our results support the socioecological hypothesis, which postulates that the different ecological niches of the two species (dogs have evolved to primarily be scavengers and thrive on and around human refuse, while wolves have evolved to primarily be group hunters and have a low hunting success rate) have, at least partly, shaped their behaviours.

Ghrelin receptor inverse agonists as a novel therapeutic approach against obesity-related metabolic disease.

AIMS: Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand-independent constitutive activity, which can be pharmacologically exploited to induce inverse ghrelin actions. Because ghrelin receptor inverse agonists (GHSR-IA) might be effective for the treatment of obesity-related metabolic disease, we tested 2 novel synthetic compounds GHSR-IA1 and GHSR-IA2. MATERIALS AND METHODS: In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR-IA1 and GHSR-IA2. We used healthy mice, Zucker diabetic fatty (ZDF) rats and diet-induced obese (DIO) mice to explore effects on food intake (FI), body weight (BW), conditioned taste aversion (CTA), oral glucose tolerance (OGT), pancreatic islet morphology, hepatic steatosis (HS), and blood lipids. RESULTS: Both compounds acutely reduced FI in mice without inducing CTA. Chronic GHSR-IA1 increased metabolic rate in chow-fed mice, suppressed FI, and improved OGT in ZDF rats. Moreover, the progression of islet hyperplasia to fibrosis in ZDF rats slowed down. GHSR-IA2 reduced FI and BW in DIO mice, and reduced fasting and stimulated glucose levels compared with pair-fed and vehicle-treated mice. GHSR-IA2-treated DIO mice showed decreased blood lipids. GHSR-IA1 treatment markedly decreased HS in DIO mice. CONCLUSIONS: Our study demonstrates therapeutic actions of novel ghrelin receptor inverse agonists, suggesting a potential to treat obesity-related metabolic disorders including diabetes mellitus.