The European Clinical Trials Directive was issued in 2001 and aimed to simplify and harmonise the regulatory framework of clinical trials throughout Europe, thus stimulating European research. However, significant complexity and inconsistency remains due to disparate interpretation by EU member states. Critical care research has been particularly impacted due to variable and often restrictive consenting procedures for incapacitated subjects, with some countries requiring a court-appointed representative, while others recognise consent from family members and occasionally professional representatives. Furthermore, the absence of (...) a waiver of consent threatened to put an end to emergency research in Europe and was met with varied responses. Approval procedures by ethics committees are equally inconsistent, particularly those relating to provision of a single opinion for multi-centre trials. Although evidence is somewhat mixed, this complexity as well as a general increase in administrative and financial burden following the Directive has been shown to cause a reduction in clinical trial activity in Europe, particularly academic trials. We aim to clarify some of these inconsistent procedures, particularly those relating to informed consent of incapacitated subjects, as well as discussing some general weaknesses and possible improvements of the Directive ahead of its planned revision in 2011. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

Institutional review board delays may hinder the successful completion of federally funded research in the U.S. military. When this happens, time-sensitive, mission-relevant questions go unanswered. Research participants face unnecessary burdens and risks if delays squeeze recruitment timelines, resulting in inadequate sample sizes for definitive analyses. More broadly, military members are exposed to untested or undertested interventions, implemented by well-intentioned leaders who bypass the research process altogether. To illustrate, we offer two case examples. We posit that IRB delays often appear in (...) the service of managing institutional risk, rather than protecting research participants. Regulators may see more risk associated with moving quickly than risk related to delay, choosing to err on the side of bureaucracy. The authors of this article, all of whom are military-funded researchers, government stakeholders, and/or human subject protection experts, offer feasible recommendations to improv... (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The purpose of this study was to identify and describe published research articles that were named in official findings of scientific misconduct and to investigate compliance with the administrative actions contained in these reports for corrections and retractions, as represented in PubMed. Between 1993 and 2001, 102 articles were named in either the NIH Guide for Grants and Contracts ( Findings of Scientific Misconduct ) or the U.S. Office of Research Integrity annual reports as needing retraction or correction. In 2002, (...) 98 of the 102 articles were indexed in PubMed. Eighty-five of these 98 articles had indexed corrections: 47 were retracted; 26 had an erratum; 12 had a correction described in the comment field. Thirteen had no correction, but 10 were linked to the NIH Guide Findings of Scientific Misconduct , leaving only 3 articles with no indication of any sort of problem. As of May 2005, there were 5,393 citations to the 102 articles, with a median of 26 citations per article (range 0–592). Researchers should be alert to Comments linked to the NIH Guide as these are open access, and the Findings of Scientific Misconduct’ reports are often more informative than the statements about the retraction or correction found in the journals. (shrink)

An Enquiry into the Nature of Liberation: Bhaṭṭa Rāmakaṇṭha’s Paramokṣanirāsakārikāvṛtti, a Commentary on Sadyojyotiḥ’s Refutation of Twenty Conceptions of the Liberated State. Edited and translated by Alex Watson, Dominic Goodall, and S. L. P. Anjaneya Sarma. Collection Indologie, vol. 122. Pondicherry: Institut Français de Pondichéry, École française d’Extrême-Orient, 2013. Pp. 508. €38.

Recent findings indicate that frontal brain asymmetry may be a marker of for depression. However, the psychological predispositions that account linkage between frontal brain asymmetry and depression are unclear. approach-withdrawal hypothesis is the primary framework that has been to account for the linkages between frontal brain asymmetry and or emotional disorders. We review evidence consistent with this and suggest several directions for its extension. One such direction is to constrain the approach-withdrawal hypothesis by linking frontal asymmetry to the known functions (...) of the prefrontal cortex. On this we propose that frontal brain asymmetry may be preferentially linked processes that promote the temporal continuity and shifting of or emotional priorities and the suppression of interference by sources of motivation or emotion. We review evidence from and neurobiological studies of depression that is broadly consistent with these predictions. We emphasise the need for future studies testing our hypotheses. (shrink)

Science is not taken for granted any longer. Society, politics and the media pose critical questions tending to censorship or at least control of science. How does science respond? It cannot exist and develop without freedom, but this does not mean freedom to amass knowledge and apply technological applications at any price and without restrictions. Science should be autonomous, but is not value-free. A distintion is made between external and internal social/ethical problems. The former refer to questions of the social/ethical (...) context and consequences of scientific research, and the latter to the rules of ‘good practice’ and scientific integrity. The role of academies of science, and of associations of such academies (e.g. All European Academies (ALLEA)) in developing codes of good scientific practice and fostering a proper sense of scientific values and standards is further discussed. (shrink)

Natural scientists have proposed that humankind has entered a new geologic epoch. Termed the “Anthropocene,” this new reality revolves around the central role of human activity in multiple Earth ecosystems. That challenge requires a rethinking of social science explanations of organization and environment relationships. In this article, we discuss the need to politicize institutional theory as a means understanding “Anthropocene Society,” and in turn what that resultant society means for the Anthropocene in the natural environment. We modify the constitutive elements (...) of institutional orders and a set of main change mechanisms to explore three scenarios around which future Anthropocene Societies might be built—Collapsing Systems, Market Rules, and Cultural Re-Enlightenment. Simultaneously, we use observations from the Anthropocene to expose limitations in present institutional theory and propose extensions to remedy them. Overall, this article challenges organizational scholars to consider a new paradigm under which research in environmental sustainability and social sustainability takes place. (shrink)

Thus the passage is printed in the Teubner edition of Seneca's Dialogues by E. Hermes, who, on the strength of Aen. 8. 702 f. , adds a note on the quotation ‘versus sunt Vergilii a Seneca licenter mutati’. Now the imputation to Seneca of such gross alteration of Virgil can only be supported if we disregard or eject the evidence to the contrary. As only the last five words are actually Virgilian; as Seneca himself says ‘aput vate nostra?’; as out (...) at the beginning of the second line may introduce a second quotation ; and as est, which Gertz secluded, has a part to play if the lines are by different poets, it is safer to take a step backwards and dispose the passage thus. (shrink)

‘Shameful are the scars inflicted by the sin of fraternal strife! What has ourunconscionable generation shunned, what abomination left undone? Ourgodless soldiery has held nothing sacred. I pray that Fortune may, on a new anvil, give our blunted swords another shape, to use against Massagetae andArabs!‘.

Facing an increasing number and variety of issues with social salience, firms must determine how to engage with issues that likely have a significant impact on them. Integrating issues management and salience theories, the authors find that firms engage with socially contested issues—where there is a high degree of societal disagreement—in a different manner from issues that have social consensus, or high agreement. Examining social issue resolutions filed by shareholders from 1997 to 2009, the study finds that socially contested issues, (...) as well as those issues with social consensus, are both likely to result in engagement by the firm. For social issues with consensus, a firm is more likely to opt for a low level of shareholder engagement whereas resolutions regarding contested issues lead to engaging shareholders at a higher level. These findings shed new light on the IM and issue salience literature streams that have suggested firms will react differently to these types of issues, even while they remain largely untested. Finally, firms become less engaged with perennial issues over time. rather than more, providing new guidance to researchers, shareholder activists, and firms alike. To the authors’ knowledge, such fined-grained insight into expected levels of firm engagement with social issue salience has not been put forth previously. (shrink)

In A.D. 60 Nero instituted at Rome a quinquennale certamen which he called Neronia. It was in three sections—athletics, chariot-racing, and music —after a Greek model. This model would be that of the Pythian rather than of the Olympic Games, for at the latter there was no regular musical contest; though perhaps Nero got his immediate inspiration from the Augustalia at Naples, which was an athletic and musical festival of a religious nature.

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

Despite great advances in understanding genetic mechanisms, there still exists a bias toward equating genes with innate modules that determine important developmental events. But genes are equally relevant to understanding developmental plasticity shaped by ecological events. In other words, the term 'genetic inheritance' does not specify ontogenetic mechanisms. Here we present a case history of a species assumed to be under the control of prespecified genetic wiring to direct critical behavioral events such as communication and mating. We show, however, that (...) exogenetic processes stemming from the species's ontogenetic niche provide an alternative view of the flexibility of development especially with respect to behavioral performance. (shrink)

We accept Sunstein's claim that people often use moral heuristics to make judgments and decisions. However, in situations that include a risk of betrayal, we disagree with Sunstein about when the relevant moral heuristic may be said to “misfire.” We suggest that the moral heuristic people apply to avoid the possibility of safety-product betrayal may be reasonable.