Greece’s Three-Act Tragedy:A Simple Model of Grexit vs. Staying Afloat inside the Single Currency Area

Against the backdrop of the Greek three-act tragedy, we present a theoretical framework for studying Greece’s recent debt and currency crisis. The model is built on two essential blocks: first, erratic macroeconomic policymaking in Greece is described using a stochastic regimeswitching model; second, the euro area governments’ responses to uncertain macroeconomic policies in Greece are considered. The model’s mechanism and assumptions allow either for a Grexit from the euro area or, conversely, the avoidance of Greece’s default against its creditors. The model also offers useful guidance to understand key drivers of the long-winded negotiations between the Syiza government and the euro area governments

PROTOCOL: Residential energy efficiency interventions: An effectiveness systematic review

This review aims to identify, appraise and synthesise the evidence available on the effectiveness of energy efficiency measure installations, including those bundled with behavioural interventions. The synthesis will estimate the overall impact of these interventions as well as examine possible causes of variation in impacts. We will also attempt to assess the cost-effectiveness of residential energy efficiency interventions

Energy efficiency in the British housing stock: Energy demand and the Homes Energy Efficiency Database

The UK Government has unveiled an ambitious retrofit programme that seeks significant improvement to the energy efficiency of the housing stock. High quality data on the energy efficiency of buildings and their related energy demand is critical to supporting and targeting investment in energy efficiency. Using existing home improvement programmes over the past 15 years, the UK Government has brought together data on energy efficiency retrofits in approximately 13 million homes into the Homes Energy Efficiency Database (HEED), along with annual metered gas and electricity use for the period of 2004–2007. This paper describes the HEED sample and assesses its representativeness in terms of dwelling characteristics, the energy demand of different energy performance levels using linked gas and electricity meter data, along with an analysis of the impact retrofit measures has on energy demand. Energy savings are shown to be associated with the installation of loft and cavity insulation, and glazing and boiler replacement. The analysis illustrates this source of ‘in-action’ data can be used to provide empirical estimates of impacts of energy efficiency retrofit on energy demand and provides a source of empirical data from which to support the development of national housing energy efficiency retrofit policies

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Integrated groundwater management: An overview of concepts and challenges

Managing water is a grand challenge problem and has become one of humanity’s foremost priorities. Surface water resources are typically societally managed and relatively well understood; groundwater resources, however, are often hidden and more difficult to conceptualize. Replenishment rates of groundwater cannot match past and current rates of depletion in many parts of the world. In addition, declining quality of the remaining groundwater commonly cannot support all agricultural, industrial and urban demands and ecosystem functioning, especially in the developed world. In the developing world, it can fail to even meet essential human needs. The issue is: how do we manage this crucial resource in an acceptable way, one that considers the sustainability of the resource for future generations and the socioeconomic and environmental impacts? In many cases this means restoring aquifers of concern to some sustainable equilibrium over a negotiated period of time, and seeking opportunities for better managing groundwater conjunctively with surface water and other resource uses. However, there are many, often-interrelated, dimensions to managing groundwater effectively. Effective groundwater management is underpinned by sound science (biophysical and social) that actively engages the wider community and relevant stakeholders in the decision making process. Generally, an integrated approach will mean “thinking beyond the aquifer”, a view which considers the wider context of surface water links, catchment management and cross-sectoral issues with economics, energy, climate, agriculture and the environment. The aim of the book is to document for the first time the dimensions and requirements of sound integrated groundwater management (IGM). The primary focus is on groundwater management within its system, but integrates linkages beyond the aquifer. The book provides an encompassing synthesis for researchers, practitioners and water resource managers on the concepts and tools required for defensible IGM, including how IGM can be applied to achieve more sustainable socioeconomic and environmental outcomes, and key challenges of IGM. The book is divided into five parts: integration overview and problem settings; governance; socioeconomics; biophysical aspects; and modelling and decision support. However, IGM is integrated by definition, thus these divisions should be considered a convenience for presenting the topics rather than hard and fast demarcations of the topic area

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study.

INTRODUCTION:Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception. METHODS AND ANALYSIS:The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0-2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design. ETHICS AND DISSEMINATION:Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations