We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

SUMMARYThis article examines Anglo–Dutch rivalry in the Banda Islands in the period from 1609 to 1621, with a particular focus on the process of claiming initiated by the Dutch East India Company and English East India Company. Historians have paid little attention to the precise legal justifications employed by these organisations, and how they affected the outcome of events. For both companies, treaties with Asian rulers and peoples were essential in staking out claims to trade and territory. Because so many (...) different parties were involved, individual documents had to serve multiple purposes, both on the ground in the East Indies and at the negotiating tables back in Europe. Whenever a VOC or EIC official presented a treaty to a Bandanese leader, he had to recognise local power structures in the Spice Islands, but also needed to consider his European competitors in the area, his superiors in Batavia or Bantam, and the company directors back in Amsterdam or London. Consequently, the safest and most reliable course of action was to make as many arguments as possible, piling them on top of one another. The result was an inherently messy process of claiming, yet one that was also clearly intelligible to most parties involved, including Asian rulers and peoples. A constantly changing legal suite extended to freedom of trade and navigation, contracts and alliances with native peoples, just war, conquest, actual possession, and the surrender of native sovereignty to European authorities. (shrink)

BackgroundThe landscape of clinical research has evolved over the past decade. With technological advances, the practice of using electronic informed consent (eIC) has emerged. However, a number of challenges hinder the successful and widespread deployment of eIC in clinical research. Therefore, we aimed to investigate the views of various stakeholders on the potential advantages and challenges of eIC.MethodsSemi-structured interviews were conducted with 39 participants from 5 stakeholder groups from across 11 European countries. The stakeholder groups included physicians, patient organization representatives, (...) regulator representatives, ethics committee members, and pharmaceutical industry representatives, and all were involved in clinical research. Interviews were analyzed using the framework method.ResultsInterviewees identified that a powerful feature of eIC is its personalized approach as it may increase participant empowerment. However, they identified several ethical and practical challenges, such as ensuring research participants are not overloaded with information and offering the same options to research participants who would prefer a paper-based informed consent rather than eIC. According to the interviewees, eIC has the potential to establish efficient long-term interactions between the research participants and the research team in order to keep the participants informed during and after the study. Interviewees emphasized that a personal interaction with the research team is of utmost importance and this cannot be replaced by an electronic platform. In addition, interviewees across the stakeholder groups supported the idea of having a harmonized eIC approach across the European Member States.ConclusionsInterviewees reported a range of design and implementation challenges which needs to be overcome to foster innovation in informing research participants and obtaining their consent electronically. It was considered important that the implementation of eIC runs alongside the face-to-face contact between research participants and the research team. Moreover, interviewees expect that eIC could offer the opportunity to enable a personalized approach and to strengthen continuous communication over time. If successfully implemented, eIC may facilitate the engagement of research participants in clinical research. (shrink)

As the new Editor-in-Chief (EiC) of the AJOB Neuroscience, I am aware that I have some very large shoes to fill. Paul Root Wolpe, who established the quality of the journal and served in that posit...

The article covers electronic informed consent from different dimensions so that practitioners might understand the history, regulation, and current status of eIC. It covers the transition of informed consent to electronic screens and the implications of that transition in terms of design, costs, and data analysis. The article explores the limits of regulation mandating eIC for mobile application research, and addresses some of the broader social context around eIC.

The early East India Company (EIC) had a profound effect on London, filling the British capital with new things, ideas and people; altering its streets; and introducing exotic plants and animals. Company commodities – from saltpetre to tea to opium – were natural products and the EIC sought throughout the period to understand how to produce and control them. In doing so, the company amassed information, designed experiments and drew on the expertise of people in the settlements and of individuals (...) and institutions in London. Frequent collaborators in London included the Royal Society and the Society of Apothecaries. Seeking success in the settlements and patronage in London, company servants amassed large amounts of data concerning natural objects and artificial practices. Throughout the seventeenth and eighteenth centuries, company scholars and their supporters in London sought to counter critiques of the EIC by demonstrating the utility to the nation of the objects and ideas they brought home. The EIC transformed itself several times between 1600 and 1800. Nonetheless, throughout the seventeenth and eighteenth centuries, its knowledge culture was characterized by reliance on informal networks that linked the settlements with one another and with London. (shrink)