Dobutamine stress MRI in pulmonary hypertension: relationships between stress pulmonary artery relative area change, RV performance, and 10-year survival

In pulmonary hypertension (PH), right ventricular (RV) performance determines survival. Pulmonary artery (PA) stiffening is an important biomechanical event in PH and also predicts survival based on the PA relative area change (RAC) measured at rest using magnetic resonance imaging (MRI). In this exploratory study, we sought to generate novel hypotheses regarding the influence of stress RAC on PH prognosis and the interaction between PA stiffening, RV performance and survival. Fifteen PH patients underwent dobutamine stress-MRI (ds-MRI) and right heart catheterization. RACREST, RACSTRESS, and ΔRAC (RAC STRESS – RAC REST) were correlated against resting invasive hemodynamics and ds-MRI data regarding RV performance and RV-PA coupling efficiency (n’vv [RV stroke volume/RV end-systolic volume]). The impact of RAC, RV data, and n’vv on ten-year survival were determined using Kaplan–Meier analysis. PH patients with a low ΔRAC (<−2.6%) had a worse long-term survival (log-rank P = 0.045, HR for death = 4.46 [95% CI = 1.08–24.5]) than those with ΔRAC ≥ −2.6%. Given the small sample, these data should be interpreted with caution; however, low ΔRAC was associated with an increase in stress diastolic PA area indicating proximal PA stiffening. Associations of borderline significance were observed between low RACSTRESS and low n’vvSTRESS, Δη’VV, and ΔRVEF. Further studies are required to validate the potential prognostic impact of ΔRAC and the biomechanics potentially connecting low ΔRAC to shorter survival. Such studies may facilitate development of novel PH therapies targeted to the proximal PA

House price Keynesianism and the contradictions of the modern investor subject

This article conceptualises the marked downturn in UK house prices in the 2007-2009 period in relation to longer-term processes of national economic restructuring centred on a new model of homeownership. The structure of UK house prices has been impacted markedly by the Labour Government‟s efforts to ingrain a particular notion of financial literacy amid the move towards an increasingly asset-based system of welfare. New model welfare recipients and new model homeowners have thereby been co-constituted in a manner consistent with a new UK growth regime of „house price Keynesianism‟. However, the investor subjects who drive such growth are necessarily rendered uncertain as compared with the idealised image of Government policy because of their reliance on the credit-creating decisions of private financial institutions. The recent steep decline in UK house prices is explained here as an epiphenomenon of the disruptive effect on the idealised image caused by the dependence of investor subjects on pricing dynamics not of their making

Patterning and process parameter effects in 3D suspension near-field electrospinning of nanoarrays

The extracellular matrix (ECM) contains nanofibrous proteins and proteoglycans. Nanofabrication methods have received growing interest in recent years as a means of recapitulating these elements within the ECM. Near-field electrospinning (NFES) is a versatile fibre deposition method, capable of layer-by-layer nano-fabrication. The maximum layer height is generally limited in layer-by-layer NFES as a consequence of electrostatic effects of the polymer at the surface, due to residual charge and polymer dielectric properties. This restricts the total volume achievable by layer-by-layer techniques. Surpassing this restriction presents a complex challenge, leading to research innovations aimed at increasing patterning precision, and achieving a translation from 2D to 3D additive nanofabrication. Here we investigated a means of achieving this translation through the use of 3D electrode substrates. This was addressed by in-house developed technology in which selective laser melt manufactured standing pillar electrodes were combined with a direct suspension near-field electrospinning (SNFES) technique, which implements an automated platform to manoeuvre the pillar electrodes around the emitter in order to suspend fibres in the free space between the electrode support structures. In this study SNFES was used in multiple operation modes, investigating the effects of varying process parameters, as well as pattern variations on the suspended nanoarrays. Image analysis of the nanoarrays allowed for the assessment of fibre directionality, isotropy, and diameter; identifying optimal settings to generate fibres for tissue engineering applications

High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling

To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression

A Novel In Vivo Approach to Assess Radial and Axial Distensibility of Large and Intermediate Pulmonary Artery Branches

Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA distensibility protects the right ventricle (RV) from excessive increases in pressure. Loss of PA distensibility plays a critical role in the fatal progression of pulmonary arterial hypertension (PAH) toward RV failure. However, it is unclear how PA distensibility is distributed across the generations of PA branches, mainly because of the lack of appropriate in vivo methods to measure distensibility of vessels other than the large, conduit PAs. In this study, we propose a novel approach to assess the distensibility of individual PA branches. The metric of PA distensibility we used is the slope of the stretch ratio-pressure relationship. To measure distensibility, we combined invasive measurements of mean PA pressure with angiographic imaging of the PA network of six healthy female dogs. Stacks of 2D images of the PAs, obtained from either contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface models of the PA network, from the first bifurcation down to the sixth generation of branches. For each branch of the PA, we calculated radial and longitudinal stretch between baseline and a pressurized state obtained via acute embolization of the pulmonary vasculature. Our results indicated that large and intermediate PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial distensibility data, albeit affected by larger variability, suggested that the PAs distal to the first generation may not significantly elongate in vivo, presumably due to spatial constraints. Results from both angiographic techniques were comparable to data from established phase-contrast (PC) magnetic resonance imaging (MRI) and ex vivo mechanical tests, which can only be used in the first branch generation. Our novel method can be used to characterize PA distensibility in PAH patients undergoing clinical right heart catheterization (RHC) in combination with MRI

Análisis general de sistemas productivos claves y sus indicadores a nivel nacional en el contexto de crecimiento verde

El concepto de crecimiento verde fue incluido en el Plan Nacional de Desarrollo 2014-2018 “Todos por un Nuevo País” con el objetivo de buscar el desarrollo económico sostenible, la competitividad y la reducción de vulnerabilidades al cambio climático. En este informe se busca dar a conocer el estado actual de los indicadores de crecimiento verde para diferentes sistemas productivos agropecuarios en Colombia e identificar las opciones tecnológicas que permitan mejorar dichos indicadores con el fin de incrementar la productividad de la tierra sin afectar los demás indicadores de crecimiento verde. Para lograr esto se han propuesto en este estudio cinco fases que van desde la fase de preparación, un análisis general a nivel nacional, un análisis detallado a nivel regional, un análisis de barreras para la implementación de medidas y recomendaciones. Este reporte corresponde a la fase dos del estudio sobre análisis general. La línea base de expansión en área proyectada para los cinco sistemas productivos, la construcción y estimación de los indicadores a nivel nacional para cada uno de los sistemas productivos y una lista de opciones tecnológicas que pueden contribuir al crecimiento verde en estos sistemas productivos. Posteriormente se estimará el potencial que tiene cada tecnología sobre los indicadores de crecimiento verde. En este estudio también se incluye la metodología y resultados sobre el proceso de priorización de los sistemas productivos. The concept of green growth was included in the National Development Plan 2014-2018 "All for a New Country" with the objective of seeking sustainable economic development, competitiveness and the reduction of vulnerabilities in climate change. This report seeks to publicize the current status of green growth indicators for different agricultural production systems in Colombia and identify the technological options that allow improving the indicators in order to increase the productivity of the land without affecting the other indicators of green growth To achieve this, five phases have been improved in this study, ranging from the preparation phase, a general analysis at the national level, detailed analysis at the regional level, an analysis of barriers to the implementation of measures and recommendations. This report corresponds to the phase of the study on general analysis. The baseline projected in this area for the five productive systems, the construction and the estimation of the indicators at national level for each one of the productive systems and a list of technological options that can contribute to the green growth in these productive systems. Subsequently, the potential of each technology on green growth indicators will be estimated. This study also includes the methodology and results on the process of prioritization of productive systems.The concept of green growth was included in the National Development Plan 2014-2018 "All for a New Country" with the objective of seeking sustainable economic development, competitiveness and the reduction of vulnerabilities in climate change. This report seeks to publicize the current status of green growth indicators for different agricultural production systems in Colombia and identify the technological options that allow improving the indicators in order to increase the productivity of the land without affecting the other indicators of green growth To achieve this, five phases have been improved in this study, ranging from the preparation phase, a general analysis at the national level, detailed analysis at the regional level, an analysis of barriers to the implementation of measures and recommendations. This report corresponds to the phase of the study on general analysis. The baseline projected in this area for the five productive systems, the construction and the estimation of the indicators at national level for each one of the productive systems and a list of technological options that can contribute to the green growth in these productive systems. Subsequently, the potential of each technology on green growth indicators will be estimated. This study also includes the methodology and results on the process of prioritization of productive systems