Wavefront curvature sensing for the human eye

In this paper we present a curvature wavefront sensor for the eye. The layout proposed is novel, whilst the algorithm used has been adapted from previously published work [Roddier, F.; Roddier, C. Appl. Opt. 1991, 30, 1325–1327]. The design of the set-up incorporates two field lenses that, together with a beam separator, define the distance Δz between the two sampled planes. We present a feasibility study to use this particular combination of optical configuration and retrieval algorithm in the eye. We present calibration curves and results from three real eyes

Loss of heterozygosity and SOSTDC1 in adult and pediatric renal tumors

<p>Abstract</p> <p>Background</p> <p>Deletions within the short arm of chromosome 7 are observed in approximately 25% of adult and 10% of Wilms pediatric renal tumors. Within Wilms tumors, the region of interest has been delineated to a 2-Mb minimal region that includes ten known genes. Two of these ten candidate genes, <it>SOSTDC1 </it>and <it>MEOX2</it>, are particularly relevant to tumor development and maintenance. This finding, coupled with evidence that SOSTDC1 is frequently downregulated in adult renal cancer and regulates both Wingless-Int (Wnt)- and bone morphogenetic protein (BMP)-induced signaling, points to a role for SOSTDC1 as a potential tumor suppressor.</p> <p>Methods</p> <p>To investigate this hypothesis, we interrogated the Oncomine database to examine the SOSTDC1 levels in adult renal clear cell tumors and pediatric Wilms tumors. We then performed single nucleotide polymorphism (SNP) and sequencing analyses of <it>SOSTDC1 </it>in 25 pediatric and 36 adult renal tumors. Immunohistochemical staining of patient samples was utilized to examine the impact of <it>SOSTDC1 </it>genetic aberrations on SOSTDC1 protein levels and signaling.</p> <p>Results</p> <p>Within the Oncomine database, we found that SOSTDC1 levels were reduced in adult renal clear cell tumors and pediatric Wilms tumors. Through SNP and sequencing analyses of 25 Wilms tumors, we identified four with loss of heterozygosity (LOH) at 7p and three that affected <it>SOSTDC1</it>. Of 36 adult renal cancers, we found five with LOH at 7p, two of which affected <it>SOSTDC1</it>. Immunohistochemical analysis of SOSTDC1 protein levels within these tumors did not reveal a relationship between these instances of <it>SOSTDC1 </it>LOH and SOSTDC1 protein levels. Moreover, we could not discern any impact of these genetic alterations on Wnt signaling as measured by altered beta-catenin levels or localization.</p> <p>Conclusions</p> <p>This study shows that genetic aberrations near <it>SOSTDC1 </it>are not uncommon in renal cancer, and occur in adult as well as pediatric renal tumors. These observations of <it>SOSTDC1 </it>LOH, however, did not correspond with changes in SOSTDC1 protein levels or signaling regulation. Although our conclusions are limited by sample size, we suggest that an alternative mechanism such as epigenetic silencing of <it>SOSTDC1 </it>may be a key contributor to the reduced SOSTDC1 mRNA and protein levels observed in renal cancer.</p

Analytic Considerations in Economic Evaluations of Multinational Cardiovascular Clinical Trials

OBJECTIVES: The growing number of economic evaluations that use data collected in multinational clinical trials raises numerous questions regarding their execution and interpretation. Although recommendations for conducting economic evaluations have been widely disseminated, relatively little guidance has been given for conducting economic evaluations alongside clinical trials, particularly multinational trials. METHODS: Building on a literature review that was conducted in preparation for an expert workshop, we evaluated a subset of methodological issues related to conducting economic evaluations alongside multinational clinical trials. RESULTS: We found wide variation in the types of costs included as part of the analyses and in the methods used to assign costs to hospitalization events. Furthermore, we found that the extrapolation of costs and survival outcomes beyond the trial period is an inconsistent practice and is often not dependent on whether a survival benefit was observed in the trial or on the epidemiology or practice patterns in the country to which the findings are directed. CONCLUSIONS: Although the limited sample size precluded a quantitative analysis of trial characteristics and their associations with the methodologies employed, our findings highlight the need for more guidance to analysts regarding the execution of economic evaluations using data from multinational clinical trials. As the research community grapples with the complexities of methodological and logistical issues involved in multinational economic evaluations, the development of a standardized format to report the basic methodological characteristics of such studies would help to improve transparency and comparability for other analysts and decision-makers

How to prioritize bridge maintenance using a functional priority index

The progressive aging of civil infrastructures makes it essential to develop managerial tools and instrument for planning maintenance activities. As public entities, typically in charge of the management of infrastructures, have limited resources, it is crucial to define clear prioritization criteria. Addressing this need, this work introduces the usage of a functional priority index for ranking infrastructures on the basis of the impact of their closure. The impact is expressed in terms of induced travel delay for people due to path detour. To estimate this delay an analytical strategy is introduced and applied to assess the priority index on a sample of 290 bridges in Lombardy. Relevant information are gathered integrating two data sources providing information on the transportation network and on the travel demand, i.e. road network data and Origin Destination matrices. The results of this application show that the method enables the identification of the most critical infrastructures and the detection, for each bridge closure, of the most impacted areas of the region and the most impacted hours of the day

Amyloid peptide β 1-42 induces integrin α IIb β 3 activation, platelet adhesion, and thrombus formation in a NADPH Oxidase-Dependent Manner

The progression of Alzheimer's dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects of β amyloid peptides on the function of platelets, the cells driving haemostasis. Amyloid peptide β1-42 (Aβ1-42), Aβ1-40, and Aβ25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to Aβ1-42 compared to other Aβ peptides. In addition, significant platelet spreading was observed over Aβ1-42, while Aβ1-40, Aβ25-35, and the scAβ1-42 control did not seem to induce any platelet spreading, which suggested that only Aβ1-42 activates platelet signalling in our experimental conditions. Aβ1-42 also induced significant platelet adhesion and thrombus formation in whole blood under venous flow condition, while other Aβ peptides did not. The molecular mechanism of Aβ1-42 was investigated by flow cytometry, which revealed that this peptide induces a significant activation of integrin αIIbβ3, but does not induce platelet degranulation (as measured by P-selectin membrane translocation). Finally, Aβ1-42 treatment of human platelets led to detectable levels of protein kinase C (PKC) activation and tyrosine phosphorylation, which are hallmarks of platelet signalling. Interestingly, the NADPH oxidase (NOX) inhibitor VAS2870 completely abolished Aβ1-42-dependent platelet adhesion in static conditions, thrombus formation in physiological flow conditions, integrin αIIbβ3 activation, and tyrosine- and PKC-dependent platelet signalling. In summary, this study highlights the importance of NOXs in the activation of platelets in response to amyloid peptide β1-42. The molecular mechanisms described in this manuscript may play an important role in the neurovascular impairment observed in Alzheimer's patients

The transplant iron score as a predictor of stem cell transplant survival

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections

Amyloid peptide β1-42 induces integrin αIIbβ3 activation, platelet adhesion and thrombus formation in a NADPH oxidase-dependent manner

This is the final version. Available on open access from Hindawi Publishing Corporation via the DOI in this recordThe progression of Alzheimer’s dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects of β amyloid peptides on the function of platelets, the cells driving haemostasis. Amyloid peptide β1-42 (Aβ1-42), Aβ1-40, and Aβ25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to Aβ1-42 compared to other Aβ peptides. In addition, significant platelet spreading was observed over Aβ1-42, while Aβ1-40, Aβ25-35, and the scAβ1-42 control did not seem to induce any platelet spreading, which suggested that only Aβ1-42 activates platelet signalling in our experimental conditions. Aβ1-42 also induced significant platelet adhesion and thrombus formation in whole blood under venous flow condition, while other Aβ peptides did not. The molecular mechanism of Aβ1-42 was investigated by flow cytometry, which revealed that this peptide induces a significant activation of integrin αIIbβ3, but does not induce platelet degranulation (as measured by P-selectin membrane translocation). Finally, Aβ1-42 treatment of human platelets led to detectable levels of protein kinase C (PKC) activation and tyrosine phosphorylation, which are hallmarks of platelet signalling. Interestingly, the NADPH oxidase (NOX) inhibitor VAS2870 completely abolished Aβ1-42-dependent platelet adhesion in static conditions, thrombus formation in physiological flow conditions, integrin αIIbβ3 activation, and tyrosine- and PKC-dependent platelet signalling. In summary, this study highlights the importance of NOXs in the activation of platelets in response to amyloid peptide β1-42. The molecular mechanisms described in this manuscript may play an important role in the neurovascular impairment observed in Alzheimer’s patients.Alzheimer´s Research UKBritish Heart FoundationNational Institute for Health Research (NIHR

LA COERCIÓN CONSENSUADA: VIOLENCIA INSTITUCIONAL EN TERRITORIOS DE RELEGACIÓN

En este trabajo nos interesa indagar sobre el modo en que opera el control social gestionado a través de normas jurídicas, o expresado a través de la actividad estatal desplegada por sus fuerzas de seguridad. Nos interesan estos elementos cuando están encaminados a gestionar conflictos violentos y el modo en que tales prácticas y normas jurídicas son requeridas y aceptadas de manera diferencial en el seno de la sociedad. Intentaremos dar cuenta de la existencia de cambios operados en la sociedad civil respecto del tratamiento de la violencia, que emergen luego como una reacción frente a las instituciones del Estado y le reclaman a estas mayor intervención coercitiva a través de normas que intensifican el control punitivo. Nos interesa también conocer el grado de operatividad de las normas jurídicas para ser aceptadas como legítimas o por el contrario conocer la capacidad de algunos grupos que las resisten mientras articulan un tipo de relación especial con las agencias estatales de seguridad, para instituir nuevas reglas que de manera contradictoria operan en sus relaciones. La cuestión de la construcción de los sujetos peligrosos por medio de maniobras que fusionan la coerción y el consenso atraviesa este trabajo pues constituye otra de las preocupaciones de nuestro equipo de investigacion. Nos interesa preguntarnos cómo se manipula el consenso en la sociedad civil para profundizar el ejercicio de la violencia (legítima o ilegítima) cuando se debe mantener el estado de cosas existente