Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Drivers of collaboration to mitigate climate change: An illustration of Swiss climate policy over 15 years

Climate change mitigation policy is driven by scientific knowledge and involves actors from the international, national and local decision-making levels. This multi-level and cross-sectoral context requires collaborative management when designing mitigation solutions over time and space. But collaboration in general policymaking settings, and particularly in the complex domain of climate mitigation, is not an easy task. This paper addresses the question of what drives collaboration among collective actors involved in climate mitigation policy. We wish to investigate whether common beliefs or power structures influence collaboration among actors. We adopt a longitudinal approach to grasp differences between the early and more advanced stages of mitigation policy design. We use survey data to investigate actors’ collaboration, beliefs and power, and apply a Stochastic Actor-oriented Model for network dynamics to three subsequent networks in Swiss climate policy between 1995 and 2012. Results show that common beliefs among actors, as well as formal power structures, have a higher impact on collaboration relations than perceived power structures. Furthermore, those effects hold true for decision-making about initial mitigation strategies, but less so for the implementation of those measures.

Jewish life in oriental countries : a list of books and manuscripts exhibited at the New York public library March 30th to December 31st, 1926

Prepared and arranged by Joshua Bloch

A guide to reading in social ethics and allied subjects: lists of books and articles selected and described for the use of general readers

by teachers in Harvard University.

Lists of books in the Harvard College Library, undated

This folder contains six leaves with undated book and shelf lists.

Catalog of books in the chest sent by Thomas Hollis to Boston, 1720 January 1

This one-page document contains a list of books sent to Increase Mather (1639-1723; Harvard AB 1656) by Captain Chadder on behalf of English Harvard benefactor Thomas Hollis (1659-1731).

List of books received, Oct. 24, 1763 with 1764 addition

This document also lists volumes donated by a Mr. Bradstreet and Mr. Harris, as well as a list of "books saved [from the 1764 fire] by being borrowed" by individuals named Sewall, Parker, Cushing, Appleton, Brigden, Marsh, Cooke, Bowdoin, and Chardon.

List of books received, October 1, 1766

Notation indicates that books were transported by a Captain Marshall.

List of books received, May 11, 1767(?)

The date of this list is written on the document in pencil, possibly in the hand of John Langdon Sibley. Its source and the reason for its attribution are not currently known.

List of books received, Aug. 15, 1767(?)

The date of this list is written on the document in pencil, possibly in the hand of John Langdon Sibley. Its source and the reason for its attribution are not currently known. Document indicates that books arrived "in the two Boxes marked R. O."