Molecular dynamics (MD) simulations were used to investigate the binding of four ligands to the Val122Ile mutant of the protein transthyretin. Dissociation, misfolding, and subsequent aggregation of mutated transthyretin proteins are associated with the disease Familial Amyloidal Cardiomyopathy. The ligands investigated were the drug candidate AG10 and its decarboxy and N-methyl derivatives along with the drug tafamidis. These ligands bound to the receptor in two halogen binding pockets (HBP) designated AB and A'B'. Inter-ligand distances, solvent accessible surface areas, root mean squared deviation measurements, and extracted structures showed very little change in the AG10 ligands' conformations or locations within the HBP during the MD simulation. In addition, the AG10 ligands experienced stable, two-point interactions with the protein by forming hydrogen bonds with Ser-117 residues in both the AB and A'B' binding pockets and Lysine-15 residues found near the surface of the receptor. Distance measurements showed these H-bonds formed simultaneously during the MD simulation. Removal of the AG10 carboxylate functional group to form decarboxy-AG10 disrupted this two-point interaction causing the ligand in the AB pocket to undergo a conformational change during the MD simulation. Likewise, addition of a methyl group to the AG10 hydrazone functional group also disrupted the two-point interaction by decreasing hydrogen bonding interactions with the receptor. Finally, MD simulations showed that the tafamidis ligands experienced fewer hydrogen bonding interactions than AG10 with the protein receptor. The tafamidis ligand in pocket A'B' was also found to move deeper into the HBP during the MD simulation. © 2019 Published by Elsevier B.V.STUDY QUESTION Does In vitro maturation (IVM) of immature oocytes affect health, including growth at 2 years of age, in singletons born to mothers with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER This study of 92 singletons born after IVM in mothers with PCOS showed no significant differences in anthropometry and health outcome parameters in comparison with a cohort of 74 peers born after intracytoplasmic sperm injection (ICSI) and conventional controlled ovarian stimulation (COS) in mothers with PCOS. WHAT IS KNOWN ALREADY IVM has been used worldwide in women with PCOS. However, the paucity of available data related to children's health following IVM is an important impediment to a more widespread use of the technology. Although previous reports on the neonatal outcome after IVM are generally reassuring, these studies have flaws that hamper the interpretation of outcomes. Moreover, few studies have reported on health outcomes after IVM beyond infancy, and particularly growth data in children born after The Universitair Ziekenhuis Brussel (UZ Brussel) and the Center for Medical Genetics have received several educational grants from IBSA, Ferring, MSD and Merck for establishing the database for follow-up research and organizing the data collection. Published byOxford University Press on behalf of the European Society of Human Reproduction and Embryology.Background Large-scale data collection is an increasingly prominent and influential feature of efforts to improve healthcare delivery, yet securing the involvement of clinical centres and ensuring data comprehensiveness often proves problematic. We explore how improvements in both data submission and completion rates were achieved during a crucial period of the evolution of two large-scale data exercises. H1152 Methods  As part of an evaluation of a quality improvement programme, we conducted an ethnographic study involving 90 interviews and 47 days of non-participant observation of two UK national clinical audits in a period before submission of data on adherence to clinical standards became mandatory. Results Critical to the improvements in submission and completion rates in the two exercises were the efforts of clinical leaders to refigure "data work" as a professionalization strategy. Using a series of strategic manoeuvres, leaders constructed a cultural account that tied the fortunes of the healthcare professions to the submission of high-quality data, proposing that it would demonstrate responsibility, transparency, and alignment with the public interest. In so doing, clinical leadership deployed tactics that might have been seen as unwarranted managerial aggression had they been imposed by parties external to the profession. Many residual challenges were linked not to principled objection by clinicians, but to mundane problems and frustrations in obtaining, recording, and submitting data. The cultural framing of data work as a professional duty was important to resolving its status as an abject form of labour. Conclusions Improving data quality in large-scale exercises is possible, but requires cooperation with clinical centres. Enabling professional leadership of data work may offer some significant advantages, but attention is also needed to mundane and highly consequential obstacles to participation in data collection. Copyright © 2019 Dixon-Woods M et al.There is a dearth of freely-available, standardised open source analysis tools available for the analysis of neuronal signals recorded in vivo in the freely-behaving animal. In response, we have developed a freely-available, open-source toolbox, NeuroChaT ( Neuron Characterisation Toolbox), specifically addressing this lacuna. Although we have particularly emphasised single unit analyses for spatial coding, NeuroChaT also characterises rhythmic properties of units and their dynamics associated with local field potential signals. NeuroChaT was developed using Python and facilitates a complete pipeline from automation of analysis to producing and managing publication-quality figures. Additionally, we have adopted a platform-independent format (Hierarchical Data Format version 5) for storing recorded and analysed data. By providing an easy-to-use software package, we aim to simplify the adoption of standardised analyses for behavioural neurophysiology and facilitate open data sharing and collaboration between laboratories.