Janus kinase inhibition and its effect upon the therapeutic landscape for myelofibrosis:from palliation to cure?

Following the discovery of the Janus kinase (JAK) 2 V617F mutation in 2005 the explosion of research and drug development activity has not only advanced our understanding of the pathogenesis of myeloproliferative neoplasms (MPNs) but also triggered debate about classification, allowed revised diagnostic and response criteria, provided a target for treatment and a mode of monitoring its success. These changes and the resultant clinical research are discussed in this article where we argue that discovery of the JAK2 V617F mutation has signalled the much delayed change in therapeutic paradigm for myelofibrosis and possibly other MPNs from palliation and allowing us to move closer to, but not yet attain, a cure.

Pain in the preterm neonate:behavioural and physiological indices

The impact of invasive procedures on preterm neonates has received little systematic attention. We examined facial activity, body movements, and physiological measures in 56 preterm and full-term newborns in response to heel lancing, along with comparison preparatory and recovery intervals. The measures were recorded in special care and full-term nurseries during routine blood sampling. Data analyses indicated that in all measurement categories reactions of greatest magnitude were to the lancing procedure. Neonates with gestational ages as short as 25-27 weeks displayed physiological responsivity to the heel lance, but only in the heart rate measure did this vary with gestational age. Bodily activity was diminished in preterm neonates in general, relative to full-term newborns. Facial activity increased with the gestational age of the infant. Specificity of the response to the heel lance was greatest on the facial activity measure. Identification of pain requires attention to gestational age in the preterm neonate.

Late Pleistocene climate change and landscape dynamics in the Eastern Alps: the inner-alpine Unterangerberg record (Austria)

Drill cores from the inner-alpine valley terrace of Unterangerberg, located in the Eastern Alps of Austria, offer first insights into a Pleistocene sedimentary record that was not accessible so far. The succession comprises diamict, gravel, sand, lignite and thick, fine grained sediments. Additionally, cataclastic deposits originating from two paleo-landslide events are present. Multi-proxy analyses including sedimentological and palynological investigations as well as radiocarbon and luminescence data record the onset of the last glacial period (Wurmian) at Unterangerberg at similar to 120-110 ka. This first time period, correlated to the MIS 5d, was characterised by strong fluvial aggradation under cold climatic conditions, with only sparse vegetation cover. Furthermore, two large and quasi-synchronous landslide events occurred during this time interval. No record of the first Early Wiirmian interstadial (MIS 5c) is preserved. During the second Early Wiirmian interstadial (MIS 5a), the local vegetation was characterised by a boreal forest dominated by Picea, with few thermophilous elements. The subsequent collapse of the vegetation is recorded by sediments dated to similar to 70-60 ka (i.e. MIS 4), with very low pollen concentrations and the potential presence of permafrost. Climatic conditions improved again between similar to 55 and 45 ka (MIS 3) and cold-adapted trees re-appeared during interstadials, forming an open forest vegetation. MIS 3 stadials were shorter and less severe than the MIS 4 at Unterangerberg, and vegetation during these cold phases was mainly composed of shrubs, herbs and grasses, similar to what is known from today's alpine timberline. The Unterangerberg record ended at similar to 45 ka and/or was truncated by ice during the Last Glacial Maximum. (C) 2013 Elsevier Ltd. All rights reserved.

Papers in Italian Archaeology IV - Vol 1 Landscape in Italian Archaeology:The Cambridge Conference

Malone, C.A.T. and S.K.F. Stoddart. (eds.). IV. S243 1985. Cambridge: British Archaeological Reports.

Power in Context: the Lismore landscape project.

Redhouse, D.I., Anderson, M., Cockerell, T., Gilmour, S., Housley, R., *Malone, C., *Stoddart,S.

Data Structure Report of the Lismore Landscape project.: Submitted to Historic Scotland. 2004, Historic Scotland: Edinburgh.

Stoddart, S. and C. Malone,

Data Structure Report of the Lismore Landscape project.:Submitted to Historic Scotland.

Stoddart, S., C. Malone, and D. Redhouse, 2005.

In search of common grounds: Stitching the divided landscape of urban parks in Belfast's interface zones

Political and spatial contestation in divided cities contributes to strategies of self-defense that utilize physical and spatial settings to enable the constitution of social boundaries, borders and territories.
Urban parks that are designed to ease division through an open transitional landscape can instead facilitate further segregation through their spatial order and facility layout. This paper investigates the role of the spatial design and material landscape of integrated parks in Belfast interface areas as instruments of engagement or division. It does so by analyzing the spatial organization of the parks’ facilities and the resultant ‘social voids.’ Space, time and distance were found to be effective tools for the negotiation of privacy, the manifestation of power, and the interplay of dominance and self-confidence. In the context of a divided city, strong community-culture tends to reproduce new boundaries and territories within the shared landscape. Through user interviews and spatial analysis, this paper outlines the design principles that influence spatial behavior in the urban parks of contested urban landscapes. It argues that despite granting equal access to shared public facilities, social voids and physical gaps can instill practices of division that deepen territorial barriers, both psychologically and spatially.

Response of farmland biodiversity to the introduction of bioenergy crops: effects of local factors and surrounding landscape context

The recent growth in bioenergy crop cultivation, stimulated by the need to implement measures to reduce net CO emissions, is driving major land-use changes with consequences for biodiversity and ecosystem service provision. Although the type of bioenergy crop and its associated management is likely to affect biodiversity at the local (field) scale, landscape context and its interaction with crop type may also influence biodiversity on farms. In this study, we assessed the impact of replacing conventional agricultural crops with two model bioenergy crops (either oilseed rape Brassica napus or Miscanthus × giganteus) on vascular plant, bumblebee, solitary bee, hoverfly and carabid beetle richness, diversity and abundance in 50 sites in Ireland. We assessed whether within-field biodiversity was also related to surrounding landscape structure. We found that local- and landscape-scale variables correlated with biodiversity in these agricultural landscapes. Overall, the differences between the bioenergy crops and the conventional crops on farmland biodiversity were mostly positive (e.g. higher vascular plant richness in Miscanthus planted on former conventional tillage, higher solitary bee abundance and richness in Miscanthus and oilseed rape compared with conventional crops) or neutral (e.g. no differences between crop types for hoverflies and bumblebees). We showed that these crop type effects were independent of (i.e. no interactions with) the surrounding landscape composition and configuration. However, surrounding landscape context did relate to biodiversity in these farms, negatively for carabid beetles and positively for hoverflies. Although we conclude that the bioenergy crops compared favourably with conventional crops in terms of biodiversity of the taxa studied at the field scale, the effects of large-scale planting in these landscapes could result in very different impacts. Maintaining ecosystem functioning and the delivery of ecosystem services will require a greater understanding of impacts at the landscape scale to ensure the sustainable development of climate change mitigation measures.