Dkk4 and Eda Regulate Distinctive Developmental Mechanisms for Subtypes of Mouse Hair

The mouse hair coat comprises protective “primary” and thermo-regulatory “secondary” hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda-/y) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda

Electronic Cigarettes Regulation in the UK: A Case Study in Evidence Informed Policy Making

This chapter argues that policy debates on electronic cigarettes (e-cigarettes) are structured around competing evidence claims between proponents and sceptics, who remain bitterly divided on the issue. The confusion and intransigence which has emerged between these camps is, in part, the result of an insufficiently nuanced understanding of the value-centred and highly political nature of the policy process, and the highly circumscribed (yet nonetheless important) role which evidence can play within this. Key policy actors, often from biomedical backgrounds, or trained in the natural sciences, have been unable to recognise the limits of evidence to resolve protracted policy controversies such as that surrounding e-cigarettes. The chapter highlights the value of insights, derived from interpretative social science, about the multiple potential framings of an issue and the need for reflexivity on the part of policy actors to move beyond the current impasse

Children at high altitude: an international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001.

International audienceThis article presents a cartographic system to facilitate cooperative manoeuvres among autonomous vehicles in a well-known environment. The main objective is to design an extended cartographic system to help in the navigation of autonomous vehicles. This system has to allow the vehicles not only to access the reference points needed for navigation, but also noticeable information such as the location and type of traffic signals, the proximity to a crossing, the streets en route, etc. To do this, a hierarchical representation of the information has been chosen, where the information has been stored in two levels. The lower level contains the archives with the Universal Traverse Mercator (UTM) coordinates of the points that define the reference segments to follow. The upper level contains a directed graph with the relational database in which streets, crossings, roundabouts and other points of interest are represented. Using this new system it is possible to know when the vehicle approaches a crossing, what other paths arrive at that crossing, and, should there be other vehicles circulating on those paths and arriving at the crossing, which one has the highest priority. The data obtained from the cartographic system is used by the autonomous vehicles for cooperative manoeuvres

Building global development strategies for cf therapeutics during a transitional cftr modulator era

As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies. To this end, we must identify areas for which harmonization is lacking and for which efficiencies can be gained to promote ethical, feasible, and credible study designs amidst the changing CF care landscape. This article summarizes the counsel from core advisors across multiple international regions and clinical trial networks, developed during a one-day workshop in October 2019. The goal of the workshop was to identify, in consideration of the highly transitional era of CFTR modulator availability, the drug development areas for which global alignment is currently uncertain, and paths forward that will enable advancement of CF therapeutic development. (C) 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved