When dissimilar images are presented to the two eyes, binocular rivalry (BR) occurs, and perception alternates spontaneously between the images. Although neural correlates of the oscillating perception during BR have been found in multiple sites along the visual pathway, the source of BR dynamics is unclear. Psychophysical and modeling studies suggest that both low- and high-level cortical processes underlie BR dynamics. Previous neuroimaging studies have demonstrated the involvement of high-level regions by showing that frontal and parietal cortices responded time locked (...) to spontaneous perceptual alternation in BR. However, a potential contribution of early visual areas to BR dynamics has been overlooked, because these areas also responded to the physical stimulus alternation mimicking BR. In the present study, instead of focusing on activity during perceptual switches, we highlighted brain activity during suppression periods to investigate a potential link between activity in human early visual areas and BR dynamics. We used a strong interocular suppression paradigm called continuous flash suppression to suppress and fluctuate the visibility of a probe stimulus and measured retinotopic responses to the onset of the invisible probe using functional MRI. There were ∼130-fold differences in the median suppression durations across 12 subjects. The individual differences in suppression durations could be predicted by the amplitudes of the retinotopic activity in extrastriate visual areas (V3 and V4v) evoked by the invisible probe. Weaker responses were associated with longer suppression durations. These results demonstrate that retinotopic representations in early visual areas play a role in the dynamics of perceptual alternations during BR. (shrink)

We present some ideas on logical process descriptions, using relations from the DIO (Drug Interaction Ontology) as examples and explaining how these relations can be naturally decomposed in terms of more basic structured logical process descriptions using terms from linear logic. In our view, the process descriptions are able to clarify the usual relational descriptions of DIO. In particular, we discuss the use of logical process descriptions in proving linear logical theorems. Among the types of reasoning supported by DIO one (...) can distinguish both (1) basic reasoning about general structures in reality and (2) the domain-specific reasoning of experts. We here propose a clarification of this important distinction between (realist) reasoning on the basis of an ontology and rule-based inferences on the basis of an expert’s view. (shrink)

I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University (...) (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)