Trends and Cycles : an Historical Review of the Euro Area.

We analyze the euro area business cycle in a medium scale DSGE model where we assume two stochastic trends: one on total factor productivity and one on the inflation target of the central bank. To justify our choice of integrated trends, we test alternative specifications for both of them. We do so, estimating trends together with the model's structural parameters, to prevent estimation biases. In our estimates, business cycle fluctuations are dominated by investment specific shocks and preference shocks of households. Our results cast doubts on the view that cost push shocks dominate economic fluctuations in DSGE models and show that productivity shocks drive fluctuations on a longer term. As a conclusion, we present our estimation's historical reading of the business cycle in the euro area. This estimation gives credible explanations of major economic events since 1985.New Keynesian model, Business Cycle, Bayesian estimation.

Aging and passivation of magnetic properties in Co/Gd bilayers

Synthetic ferrimagnets based on Co and Gd bear promise for directly bridging the gap between volatile information in the photonic domain and non-volatile information in the magnetic domain, without the need for any intermediary electronic conversion. Specifically, these systems exhibit strong spin-orbit torque effects, fast domain wall motion and single-pulse all-optical switching of the magnetization. An important open challenge to bring these materials to the brink of applications is to achieve long-term stability of their magnetic properties. In this work, we address the time-evolution of the magnetic moment and compensation temperature of magnetron sputter grown Pt/Co/Gd trilayers with various capping layers. Over the course of three months, the net magnetic moment and compensation temperature change significantly, which we attribute to quenching of the Gd magnetization. We identify that intermixing of the capping layer and Gd is primarily responsible for this effect, which can be alleviated by choosing nitrides for capping as long as reduction of nitride to oxide is properly addressed. In short, this work provides an overview of the relevant aging effects that should be taken into account when designing synthetic ferrimagnets based on Co and Gd for spintronic applications.Comment: 9 pages, 5 figure

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

<p>Abstract</p> <p>Background</p> <p>Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.</p> <p>Methods</p> <p>Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm²for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to <it>in vivo </it>studies on pig esophagi.</p> <p>Results</p> <p>Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases.</p> <p>Conclusion</p> <p>This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.</p

High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series

BACKGROUND: The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy. METHODS: An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated. RESULTS: A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135-759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P = 0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir <= 0.5 mu g ml(-1) at 12 months, with 57.8% achieving <= 0.2 mu g ml(-1). Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 mu g ml(-1) or negative biopsy if nadir not achieved) after one HIFU session in 92.4% ( 159 out of 172) of patients. CONCLUSION: HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment. British Journal of Cancer (2009) 101, 19-26. doi: 10.1038/sj.bjc.6605116 www.bjcancer.com Published online 9 June 2009 (C) 2009 Cancer Research U

CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L, and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway may be attractive therapeutic approach for SLE treatment

CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation

Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca2+-dependent protein that promotes NF-κB-dependent endothelial cell activation, Ccl2 induction and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the prometastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

Background: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial injury and extensive inflammation of the pulmonary parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling in ARDS provide insights into understanding of molecular mechanisms of the pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA interactions in a rat model of ARDS by combining miRNA and mRNA microarray analyses.Methods: Rat model of ARDS was induced by saline lavage and mechanical ventilation. The expression profiles of both mRNAs and miRNAs in rat ARDS model were performed by microarray analyses. Microarray data were further verified by quantitative RT-PCR. Functional annotation on dys-regulated mRNAs and miRNAs was carried out by bioinformatics analysis.Results: The expression of 27 miRNAs and 37 mRNAs were found to be significantly changed. The selected miRNAs and genes were further verified by quantitative real-time PCR. The down-regulated miRNAs included miR-24, miR-26a, miR-126, and Let-7a, b, c, f. The up-regulated miRNAs were composed of miR-344, miR-346, miR-99a, miR-127, miR-128b, miR-135b, and miR-30a/b. Gene ontology and functional annotation analyses indicated that up-regulated mRNAs, such as Apc, Timp1, and Sod2, were involved in the regulation of apoptosis. Bioinformatics analysis showed the inverse correlation of altered miRNAs with the expression of their predicted target mRNAs. While Sod2 was inversely correlated with Let-7a, b, c, f., Ebf1 and Apc were inversely correlated with miR-24 and miR-26a, respectively. miR-26a, miR-346, miR-135b, miR-30a/b, miR-344, and miR-18a targeted multiple altered mRNAs. Gabrb1, Sod2, Eif2ak1, Fbln5, and Tspan8 were targeted by multiple altered miRNAs.Conclusion: The expressions of miRNAs and mRNAs were altered in a rat model of ARDS. The identified miRNA-mRNA pairs may play critical roles in the pathogenesis of ARDS.Peer reviewedPathobiologyOklahoma Center for Respiratory and Infectious DiseasesPhysiological Science

[Locally recurrent prostatic adenocarcinoma after exclusive radiotherapy: results of high intensity focused ultrasound].

OBJECTIVES: To determine the efficacy and adverse effects of high intensity focused ultrasound (HIFU) for the treatment of local recurrence of prostate cancer after exclusive external beam radiotherapy. MATERIAL AND METHODS: Seventy-two patients with histologically and biologically documented local recurrence after radiotherapy were treated by HIFU. The mean age was 68.27+/-5.93 years, and mean PSA was 6.64+/-7.26ng/ml. Thirty patients were treated according to standard parameters and 42 according to specific parameters. ASTRO 2005 criteria, specific for salvage therapy (Phoenix consensus), were used to define recurrence. Progression-free survival was calculated by the Kaplan-Meier method. RESULTS: Mean follow-up was 39+/-28 months. The negative biopsy rate was 80% and the median nadir PSA was 0.10ng/ml. Specific survival was 94% at three years and 90% at five years, and progression-free survival was 50% at three years and 44% at five years. The urinary incontinence rate was 44% (grade 1 : 12%, grade 2/3 : 32%) and the urethral stricture or bladder neck stenosis rate was 30%. The use of specific parameters reduced the incidence of severe incontinence (19% versus 50, P=0.005) and stenosis (24% versus 40). CONCLUSIONS: Treatment with HIFU achieved a five-year progression-free survival of 44%, but patients must be clearly informed about the high rate of adverse effects