Mobilizing Public Markets to Finance Renewable Energy Projects: Insights from Expert Stakeholders

Financing renewable energy projects in the United States can be a complex, time consuming, and expensive process. Currently, most equity investment in new renewable power production facilities is supported by tax credits and accelerated depreciation benefits, and is constrained by the pool of potential investors that can fully use these tax benefits and are willing to engage in complex financial structures. For debt financing, non-government lending to renewables has largely been provided by foreign banks that may be under future lending constraints due to economic and regulatory conditions.To discuss these and other renewable energy financing challenges and to identify new sources of capital to the U.S. market, two roundtable discussions were held with renewable energy and financing experts in April 2012. This report summarizes the key messages of those discussions and is designed to provide insights to the U.S. market and inform the international conversation on renewable energy financing innovations

Dynamical mean-field theory of indirect magnetic exchange

To analyze the physical properties arising from indirect magnetic exchange between several magnetic adatoms and between complex magnetic nanostructures on metallic surfaces, the real-space extension of dynamical mean-field theory (R-DMFT) appears attractive as it can be applied to systems of almost arbitrary geometry and complexity. While R-DMFT describes the Kondo effect of a single adatom exactly, indirect magnetic (RKKY) exchange is taken into account on an approximate level only. Here, we consider a simplified model system consisting of two magnetic Hubbard sites ("adatoms") hybridizing with a non-interacting tight-binding chain ("substrate surface"). This two-impurity Anderson model incorporates the competition between the Kondo effect and indirect exchange but is amenable to an exact numerical solution via the density-matrix renormalization group (DMRG). The particle-hole symmetric model at half-filling and zero temperature is used to benchmark R-DMFT results for the magnetic coupling between the two adatoms and for the magnetic properties induced in the substrate. In particular, the dependence of the local adatom and the nonlocal adatom-adatom static susceptibilities as well as the magnetic response of the substrate on the distance between the adatoms and on the strength of their coupling with the substrate is studied. We find both, excellent agreement with the DMRG data even on subtle details of the competition between RKKY exchange and the Kondo effect but also complete failure of the R-DMFT, depending on the parameter regime considered. R-DMFT calculations are performed using the Lanczos method as impurity solver. With the real-space extension of the two-site DMFT, we also benchmark a simplified R-DMFT variant.Comment: 14 pages, 8 figure

A functional genomic screen in Saccharomyces cerevisiae reveals divergent mechanisms of resistance to different alkylphosphocholine chemotherapeutic agents

The alkylphosphocholine (APC) class of antineoplastic and antiprotozoal drugs, such as edelfosine and miltefosine, are structural mimics of lyso-phosphatidylcholine (lyso-PC), and are inhibitory to the yeast Saccharomyces cerevisiae at low micromolar concentrations. Cytotoxic effects related to inhibition of phospholipid synthesis, induction of an unfolded protein response, inhibition of oxidative phosphorylation, and disruption of lipid rafts have been attributed to members of this drug class, however, the molecular mechanisms of action of these drugs remain incompletely understood. Cytostatic and cytotoxic effects of the APCs exhibit variability with regard to chemical structure, leading to differences in effectiveness against different organisms or cell types. We now report the comprehensive identification of S. cerevisiae titratableessential gene and haploid nonessential gene deletion mutants that are resistant to the APC drug miltefosine (hexadecyl-O-phosphocholine). Fifty-eight strains out of~5600 tested displayed robust and reproducible resistance to miltefosine. This gene set was heavily enriched in functions associated with vesicular transport steps, especially those involving endocytosis and retrograde transport of endosome derived vesicles to the Golgi or vacuole, suggesting a role for these trafficking pathways in transport of miltefosine to potential sites of action in the endoplasmic reticulum and mitochondrion. In addition, we identified mutants with defects in phosphatidylinositol-4-phosphate synthesis (TetO::STT4) and hydrolysis (sac1Δ), an oxysterol binding protein homolog (osh2Δ), a number of ER-resident proteins, and multiple components of the eisosome. These findings suggest that ER-plasma membrane contact sites and retrograde vesicle transport are involved in the interorganelle transport of lyso-PtdCho and related lyso-phospholipid-like analogs to their intracellular sites of cytotoxic activity

Is it enough to be willing to win or do you have to be smart? The relationship between competitive worldviews, cognitive abilities, and applicant faking in personality tests

Recent research has highlighted competitive worldviews as a key predictor of faking—the intentional distortion of answers by candidates in the selection context. According to theoretical assumptions, applicants’ abilities, and especially their cognitive abilities, should influence whether faking motivation, triggered by competitive worldviews, can be turned into successful faking behavior. Therefore, we examined the influence of competitive worldviews on faking in personality tests and investigated a possible moderation of this relationship by cognitive abilities in three independent high school and university student samples (N1 = 133, N2 = 137, N3 = 268). Our data showed neither an influence of the two variables nor of their interaction on faking behavior. We discuss possible reasons for these findings and give suggestions for further research

Short-term clinical outcomes of hip arthroscopy versus physical therapy in patients with femoroacetabular impingement: A systematic review and meta-analysis of randomized controlled trials

Background: Both physical therapy (PT) and surgery are effective in treating femoroacetabular impingement (FAI), but their relative efficacy has not been well established until recently. Several randomized controlled trials (RCTs) comparing the early clinical outcomes of these treatments have been published, with contradictory results. Purpose/Hypothesis: The purpose of this study was to perform a meta-analysis of RCTs that compared early patient-reported outcomes (PROs) of hip arthroscopy versus PT in patients with symptomatic FAI. The hypothesis was that surgical treatment of FAI leads to better short-term outcomes than PT. Study Design: Systematic review; Level of evidence, 1. Methods: In March 2019, a systematic review was performed to identify RCTs comparing hip arthroscopy and PT in patients with symptomatic FAI. A total of 819 studies were found among 6 databases; of these, 3 RCTs met eligibility (Griffin et al, 2018; Mansell et al, 2018; and Palmer et al, 2019). All 3 RCTs reported international Hip Outcome Tool--33 (iHOT-33) scores, and 2 reported Hip Outcome Score (HOS)-Activities of Daily Living (ADL) and HOS-Sport results. In a random-effects meta-analysis, between-group differences in postintervention scores were assessed according to intention-to-treat and as-treated approaches. Quality was assessed with CONSORT, CERT, TiDieR, and the Cochrane Collaboration tool. Results: The 3 RCTs included 650 patients with FAI; the mean follow-up ranged from 8 to 24 months. All studies reported PRO improvement from baseline to follow-up for both PT and surgery. The quality of the Griffin and Palmer studies was good, with minimal bias. In the Mansell study, a 70% crossover rate from PT to surgery increased the risk of bias. The meta-analysis demonstrated improved iHOT-33 outcomes with surgery compared with PT for intention-to-treat (mean difference [MD], 11.3; Conclusion: In patients with FAI, the combined results of 3 RCTs demonstrated superior short-term outcomes for surgery versus PT. However, PT did result in improved outcomes and did not appear to compromise the surgical outcomes of patients for whom therapy failed and who progressed to surgery

Projecting Pharmaceutical Expenditure in EU5 to 2021: Adjusting for the Impact of Discounts and Rebates

Within (European) healthcare systems, the main goal for pharmaceutical expenditure is cost containment. This is due to a general belief among healthcare policy makers that pharmaceutical expenditure—driven by high prices—will be unsustainable unless further reforms are enacted.The aim of the research published in this paper is to provide more realistic expectations of pharmaceutical expenditure for all key stakeholder groups by estimating pharmaceutical expenditure at ‘net’ prices. We also aim to estimate any gaps developing between list and net pharmaceutical expenditure for the EU5 countries (i.e. France, Germany, Italy, Spain, and the UK). We adjusted an established forecast of pharmaceutical expenditure for the EU5 countries, from 2017 to 2021, by reflecting discounts and rebates not previously considered, i.e. we moved from ‘list’ to ‘net’ prices, as far as data were available.We found an increasing divergence between expenditure measured at list and net prices. When the forecasts for the five countries were aggregated, the EU5 (unweighted) average historical growth (2010–2016) rate fell from 3.4% compound annual growth rate at list to 2.5% at net. For the forecast, the net growth rate was estimated at 1.5 versus 2.9% at list.Our results suggest that future growth in pharmaceutical expenditure in Europe is likely to be (1) lower than previously understood from forecasts based on list prices and (2) below predicted healthcare expenditure growth in Europe and in line with long-term economic growth rates. For policy makers concerned about the sustainability of pharmaceutical expenditure, this study may provide some comfort, in that the perceived problem is not as large as expected

Influence of patient symptoms and physical findings on general practitioners' treatment of respiratory tract infections: a direct observation study

BACKGROUND: The high rate of antibiotic prescriptions general practitioners (GPs) make for respiratory tract infections (RTI) are often explained by non-medical reasons e.g. an effort to meet patient expectations. Additionally, it is known that GPs to some extent believe in the necessity of antibiotic treatment in patients with assumed bacterial infections and therefore attempt to distinguish between viral and bacterial infections by history taking and physical examination. The influence of patient complaints and physical examination findings on GPs' prescribing behaviour was mostly investigated by indirect methods such as questionnaires. METHODS: Direct, structured observation during a winter "cough an cold period" in 30 (single handed) general practices. All 273 patients with symptoms of RTI (age above 14, median 37 years, 51% female) were included. RESULTS: The most frequent diagnoses were 'uncomplicated upper RTI/common cold' (43%) followed by 'bronchitis' (26%). On average, 1.8 (95%-confidence interval (CI): 1.7–2.0) medicines per patient were prescribed (cough-and-cold preparations in 88% of the patients, antibiotics in 49%). Medical predictors of antibiotic prescribing were pathological findings in physical examination such as coated tonsils (odds ratio (OR) 15.4, 95%-CI: 3.6–66.2) and unspecific symptoms like fatigue (OR 3.1, 95%-CI 1.4–6.7), fever (OR 2.2, 95%-CI: 1.1–4.5) and yellow sputum (OR 2.1, 95%-CI: 1.1–4.1). Analysed predictors explained 70% of the variance of antibiotic prescribing (R(2 )= 0,696). Efforts to reduce antibiotic prescribing, e.g. recommendations for self-medication, counselling on home remedies or delayed antibiotic prescribing were rare. CONCLUSIONS: Patient complaints and pathological results in physical examination were strong predictors of antibiotic prescribing. Efforts to reduce antibiotic prescribing should account for GPs' beliefs in those (non evidence based) predictors. The method of direct observation was shown to be accepted both by patients and GPs and offered detailed insights into the GP-patient-interaction

Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN

Modeling the TNFα-Induced Apoptosis Pathway in Hepatocytes

The proinflammatory cytokine TNFα fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Recently, we showed that TNFα is able to sensitize primary murine hepatocytes cultured on collagen to Fas ligand-induced apoptosis and presented a mathematical model of the sensitizing effect. Here, we analyze how TNFα induces apoptosis in combination with the transcriptional inhibitor actinomycin D (ActD). Accumulation of reactive oxygen species (ROS) in response to TNFR activation turns out to be critical for sustained activation of JNK which then triggers mitochondrial pathway-dependent apoptosis. In addition, the amount of JNK is strongly upregulated in a ROS-dependent way. In contrast to TNFα plus cycloheximide no cFLIP degradation is observed suggesting a different apoptosis pathway in which the Itch-mediated cFLIP degradation and predominantly caspase-8 activation is not involved. Time-resolved data of the respective pro- and antiapoptotic factors are obtained and subjected to mathematical modeling. On the basis of these data we developed a mathematical model which reproduces the complex interplay regulating the phosphorylation status of JNK and generation of ROS. This model was fully integrated with our model of TNFα/Fas ligand sensitizing as well as with a published NF-κB-model. The resulting comprehensive model delivers insight in the dynamical interplay between the TNFα and FasL pathways, NF-κB and ROS and gives an example for successful model integration