Estimating Prices for R&D Investment in the 2007 R&D Satellite Account

This paper is part of a series that provides the details behind the Bureau of Economic Analysis's (BEA) satellite account on research and development (R&D) activity. In the current work, the focus is on the theoretical underpinnings and empirical implementation of the R&D price index used to construct real R&D output. We examine four alternative price indexes. For each, we lay out the theoretical assumptions needed for the approach to be valid and examine how well the approach works in practice. We then compare these four alternative price indexes and explain the choice of our preferred price index.

Methodology for the Industry Estimates in the 2007 R&D Satellite Account

This paper is part of a series that provides the details behind the Bureau of Economic Analysis's (BEA) satellite account on research and development (R&D) activity. It describes the data and experimental methodology used to create the GDP-by-Industry component of the satellite account for thirteen R&D-intensive industries and an aggregation of all other for-profit industries.

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)[superscript +] macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE[superscript −/−] mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques

Volatility in the Housing Market: Evidence on Risk and Return in the London Sub-market

The impact of volatility in housing market analysis is reconsidered via examination of the risk-return relationship in the London housing market is examined. In addition to providing the first empirical results for the relationship between risk (as measured by volatility) and returns for this submarket, the analysis offers a more general message to empiricists via a detailed and explicit evaluation of the impact of empirical design decisions upon inferences. In particular, the negative risk-return relationship discussed frequently in the housing market literature is examined and shown to depend upon typically overlooked decisions concerning components of the empirical framework from which statistical inferences are drawn

Myocardial Infarction Accelerates Atherosclerosis

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, apoE$^{−/−}$ mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. The progenitors then seeded the spleen yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression

MCL-1 is essential for survival but dispensable for metabolic fitness of FOXP3+ regulatory T cells

FOXP3+ regulatory T (Treg) cells are essential for maintaining immunological tolerance. Given their importance in immune-related diseases, cancer and obesity, there is increasing interest in targeting the Treg cell compartment therapeutically. New pharmacological inhibitors that specifically target the prosurvival protein MCL-1 may provide this opportunity, as Treg cells are particularly reliant upon this protein. However, there are two distinct isoforms of MCL-1; one located at the outer mitochondrial membrane (OMM) that is required to antagonize apoptosis, and another at the inner mitochondrial membrane (IMM) that is reported to maintain IMM structure and metabolism via ATP production during oxidative phosphorylation. We set out to elucidate the relative importance of these distinct biological functions of MCL-1 in Treg cells to assess whether MCL-1 inhibition might impact upon the metabolism of cells able to resist apoptosis. Conditional deletion of Mcl1 in FOXP3+ Treg cells resulted in a lethal multiorgan autoimmunity due to the depletion of the Treg cell compartment. This striking phenotype was completely rescued by concomitant deletion of the apoptotic effector proteins BAK and BAX, indicating that apoptosis plays a pivotal role in the homeostasis of Treg cells. Notably, MCL-1-deficient Treg cells rescued from apoptosis displayed normal metabolic capacity. Moreover, pharmacological inhibition of MCL-1 in Treg cells resistant to apoptosis did not perturb their metabolic function. We conclude that Treg cells require MCL-1 only to antagonize apoptosis and not for metabolism. Therefore, MCL-1 inhibition could be used to manipulate Treg cell survival for clinical benefit without affecting the metabolic fitness of cells resisting apoptosis

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Seeds, Agricultural Systems and Socio-natures: Towards an Actor-Network Theory Informed Political Ecology of Agriculture

Agriculture has recently been the subject of considerable research and policy attention. Events such as the 2008 ‘world food price crisis’ and concerns over the future of global food security have led to calls for a ‘New Green Revolution’, with an emphasis on boosting yields through new transgenic crop varieties. However, critics have raised concerns over the growing role of global agribusiness and transnational capital in agriculture, as well as the potential social and ecological impacts of new technologies. An analysis of emerging agricultural trends thus demands a framework that is able to negotiate the complex multi-scalar interplay between environmental, technological, scientific, political and economic factors. In this paper, we focus on the potential contribution of a synthesis between political ecology and Actor–Network Theory to our understanding of agricultural networks. We review the literature with a view to teasing out key insights and sketching out future research priorities. We focus on questions surrounding power and agency, the political ecology of scale and the role of situated knowledges and practices.Natasha Watts was supported by an Economic and Social Research Council Studentship (Award KFW/301419246). Ivan Scales was supported by an Early Career Fellowship from the Centre for Research on the Arts, Social Sciences and Humanities at the University of Cambridge and a Royal Geographical Society–Institute of British Geographers. Small Research Grant.This is the author accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1111/gec3.12212/abstract

Recombination spectra of Helium-Like Ions

We calculate the recombination spectra of the He-like ions He~I, C~V, N~VI, O~VII, Ne~IX, Mg~XI, Si~XIII, S~XV, Ar~XVII, Ca~XIX, and Fe~XXV. We include the following physical processes: radiative recombination, dielectronic recombination, three-body recombination, electron impact ionization, and collisional excitation by electrons, protons, and $\alpha$-particles. The calculations account for the effects of lowering of the continuum at high densities and high density corrections to dielectronic recombination. Then we construct models for He-like ions for fast computation of their spectra. Every model includes 29 bound levels up to n=5 and 6 doubly excited levels that account for the most important satellite lines. The models are constructed in a way that allows for proper approach to LTE under appropriate conditions. These models can simultaneously solve for the H/He-like ionization balance in photoionized or collisionally ionized plasmas and compute emission spectra including the combined effects of radiative and dielectronic recombination, collisional excitation, photoionization from excited levels, fluorescence, and line trapping. The models can be used for any temperature between 100 and $10^9$K and electron densities of up to $10^{18}$ \cm3. The models can be easily used within spectral modeling codes or as stand-alone tools for spectral analysis. We present comparisons between the results of the present models and previous work. Significant differences are found between the present effective recombination rate coefficients to the $n=2$ and those of previous estimates. Later, we study various emission line ratio diagnostics under collisional ionization and photoionized conditions.Comment: 28 pages, 5 figures. To appear in the Ap