Regional index of sustainable economic well-being development project: final report

This report presents results from a development project carried out by nef (the new economics foundation) on behalf of emda (the East Midlands Development Agency) and Natural England, to improve the methodologies used in the calculation of the R-ISEW (Regional Index of Sustainable Economic Well-Being)

Ha-Ras stimulates uptake and phosphorylation of ethanolamine: inhibition by wortmannin

AbstractTransformation of NIH 3T3 fibroblasts by Ha-Ras resulted in large increases in the phosphorylation of both [14C]ethanolamine (Etn) and [14C]choline (Cho) when these precursors were added to the medium. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (P13K), preferentially decreased phosphorylation of externally added Etn in the Ha-Ras transformed, but not in the untransformed, fibroblasts. However, wortmannin had no effect on the phosphorylation of Etn formed endogenously by phorbol ester-stimulated hydrolysis of phosphatidylethanolamine. Data suggest that interaction of mutated Ras with PI3K leads to specific stimulation of Etn uptake, followed by nearly quantitative phosphorylation of Etn by a Ras-activated Cho/Etn kinase

Embracing Causal Complexity: The Emergence of a Neo-Configurational Perspective

Causal complexity has long been recognized as a ubiquitous feature underlying organizational phenomena, yet current theories and methodologies in management are for the most part not well suited to its direct study. The introduction of the Qualitative Comparative Analysis (QCA) configurational approach has led to a reinvigoration of configurational theory that embraces causal complexity explicitly. We argue that the burgeoning research using QCA represents more than a novel methodology; it constitutes the emergence of a neo-configurational perspective to the study of management and organizations that enables a fine-grained conceptualization and empirical investigation of causal complexity through the logic of set theory. In this article, we identify four foundational elements that characterize this emerging neoconfigurational perspective: 1) conceptualizing cases as set theoretic configurations; 2) calibrating cases’ memberships into sets; 3) viewing causality in terms of necessity and sufficiency relations between sets; and, 4) conducting counterfactual analysis of unobserved configurations. We then present a comprehensive review of the use of QCA in management studies that aims to capture the evolution of the neo-configurational perspective among management scholars. We close with a discussion of a research agenda that can further this neoconfigurational approach and thereby shift the attention of management research away from a focus on net effects and towards examining causal complexity

The relationship between weight loss and interleukin 6 in non-small-cell lung cancer.

Markers of the inflammatory response, interleukin 6, C-reactive protein, albumin and full blood count, were measured in non-small-cell lung cancer (NSCLC) patients (n = 21) with and without weight loss ( > 5%). There were significant increases in circulating C-reactive protein (P < 0.001), interleukin 6 (P < 0.01) and platelets (P < 0.01) in the weight-losing group. Moreover, there was a statistically significant correlation (r = 0.785, P < 0.001) between interleukin 6 and C-reactive protein concentrations. These results are consistent with interleukin 6 and the acute phase response promoting weight loss in NSCLC

Comparison of hip fracture and osteoporosis medication prescription rates across Canadian provinces

Summary The study explores osteoporosis medication prescribing across Canadian provinces and any impact on hip fracture rates. Despite a marked variation in the prescribing of such medication, there is no effect on the hip fracture rate in either gender or any age group, suggesting either poor targeting or lack of efficacy. Introduction Hip fractures are the most disabling and costly of osteoporotic fractures, and a reduction in the risk of hip fracture is an expectation of osteoporosis medications. In this study, we have compared the use of osteoporosis medication across Canadian provinces with the rate of hip fractures in the same regions. Methods Three years of hip fracture data (2007–2009 inclusive) were obtained from the Canadian Institute for Health Information for all Canadian provinces excluding Quebec. Population information was obtained from Statistics Canada and medication information from the Brogan Inc. database. Because osteoporosis medication is available daily, weekly, monthly, and yearly, medication prescriptions were converted to “units” of prescribing, so that a once a year infusion represented 365 units, a monthly prescription 30 units, and so forth. Results There is a fourfold difference in prescribing across provinces but no corresponding variation in hip fracture rate. No significant correlation exists between prescribing load and hip fracture rate. This was true for all age groups, both genders, and for both intertrochanteric and subcapital hip fracture. Conclusions We find no association between osteoporosis medication prescribing and hip fracture rate. Possible explanations include insufficient numbers of at-risk patients on treatment, inappropriate targeting, and either lack of efficacy or efficacy limited to only certain subgroups of patients such as those with demonstrable trabecular osteoporosis

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes

Investigating radiatively driven, magnetized plasmas with a university scale pulsed-power generator

We present first results from a novel experimental platform which is able to access physics relevant to topics including indirect-drive magnetised ICF; laser energy deposition; various topics in atomic physics; and laboratory astrophysics (for example the penetration of B-fields into HED plasmas). This platform uses the X-Rays from a wire array Z-Pinch to irradiate a silicon target, producing an outflow of ablated plasma. The ablated plasma expands into ambient, dynamically significant B-fields (~5 T) which are supported by the current flowing through the Z-Pinch. The outflows have a well-defined (quasi-1D) morphology, enabling the study of fundamental processes typically only available in more complex, integrated schemes. Experiments were fielded on the MAGPIE pulsed-power generator (1.4 MA, 240 ns rise time). On this machine a wire array Z-Pinch produces an X-Ray pulse carrying a total energy of ~15 kJ over ~30 ns. This equates to an average brightness temperature of around 10 eV on-target

Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis

AbstractSkeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise

Measurements of dense fuel hydrodynamics in the NIF burning plasma experiments using backscattered neutron spectroscopy

The hydrodynamics of the dense confining fuel shell is of great importance in defining the behaviour of the burning plasma and burn propagation regimes of inertial confinement fusion experiments. However, it is difficult to probe due to its low emissivity in comparison to the central fusion core. In this work, we utilise the backscattered neutron spectroscopy technique to directly measure the hydrodynamic conditions of the dense fuel during fusion burn. Experimental data is fit to obtain dense fuel velocities and apparent ion temperatures. Trends of these inferred parameters with yield and velocity of the burning plasma are used to investigate their dependence on alpha heating and low mode drive asymmetry. It is shown that the dense fuel layer has an increased outward radial velocity as yield increases showing burn has continued into re-expansion, a key signature of hotspot ignition. Comparison with analytic and simulation models show that the observed dense fuel parameters are displaying signatures of burn propagation into the dense fuel layer, including a rapid increase in dense fuel apparent ion temperature with neutron yield