995 resultados para Harrison, Frederic,


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XVII Convocatòria d’ajuts a accions de cooperació - 2009GRECDH – UPC. Improving Energy Access In Rural sub- Saharan Africa. O-006/09. Informe

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En este trabajo se revisan algunas de las aplicaciones clásicas del bootstrap al análisis de la supervivencia. Se consideran en primer lugar el estimador bootstrap de la varianza y el estimador de la mediana corregido para el sesgo del estimador de Kaplan-Meier de la función de supervivencia. A continuación se consideran algunos aspectos mas recientes, tales como métodos para construir bandas de confianza para el estimador de la funcidn de supervivencia y contrastes aproximados para la comparación de funciones de supervivencia. En ambas situaciones el bootstrap resulta de gran utilidad para la aproximación de 10s valores críticos necesarios.

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BACKGROUND: Polyomavirus-associated nephropathy (PVAN) is a serious complication and cause of graft loss in kidney transplant recipients. In the absence of specific antiviral drugs, early detection of the disease and reduction of immunosuppressive regimen is the cornerstone of therapy. Cidofovir, a nucleoside analogue, has been found to inhibit BK virus (BKV) replication in vitro and has been proposed as treatment of refractory PVAN at low doses; however, its efficacy has never been demonstrated in randomized controlled trials. METHODS: Cidofovir therapy (0.5 mg/kg at a 2-week interval for eight consecutive doses) was initiated in two patients with biopsy-proven PVAN and persistent BKV DNA viraemia (> or = 10,000 copies/ml despite sustained reduction of the immunosuppressive regimen). In addition to these two case reports, we performed a critical review of the literature on the use of cidofovir in PVAN. RESULTS: No significant decrease of BKV viral load in blood was observed during cidofovir therapy and in follow-up of the two patients treated with cidofovir. Our literature review identified 21 publications reporting the use of cidofovir for the treatment of PVAN. All were case reports or small series. The efficacy of cidofovir therapy could not be assessed in 17 of these publications because of lack of data or concomitant reduction of immunosuppressive regimen. The four remaining publications were case reports. CONCLUSIONS: In vitro and clinical data to support the efficacy of cidofovir in the treatment of PVAN are currently lacking. More promising compounds should be identified for further clinical studies.

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In France and Finland, farmer's lung disease (FLD), a hypersensitivity pneumonitis common in agricultural areas, is mainly caused by Eurotium species. The presence of antibodies in patients' serum is an important criterion for diagnosis. Our study aimed to improve the serological diagnosis of FLD by using common fungal particles that pollute the farm environment as antigens. Fungal particles of the Eurotium species were observed in handled hay. A strain of Eurotium amstelodami was grown in vitro using selected culture media; and antigen extracts from sexual (ascospores), asexual (conidia), and vegetative (hyphae) forms were made. Antigens were tested by enzyme-linked immunosorbent assay (ELISA), which was used to test for immunoglobulin G antibodies from the sera of 17 FLD patients, 40 healthy exposed farmers, and 20 nonexposed controls. The antigens were compared by receiver operating characteristic analysis, and a threshold was then established. The ascospores contained in asci enclosed within cleistothecia were present in 38% of the hay blades observed; conidial heads of aspergillus were less prevalent. The same protocol was followed to make the three antigen extracts. A comparison of the results for FLD patients and exposed controls showed the area under the curve to be 0.850 for the ascospore antigen, 0.731 for the conidia, and 0.690 for the hyphae. The cutoffs that we determined, with the standard deviation for measures being taken into account, showed 67% for sensitivity and 92% for specificity with the ascospore antigen. In conclusion, the serological diagnosis of FLD by ELISA was improved by the adjunction of ascospore antigen.

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Iowa’s spring flooding is expected to be severe, especially along the western part of the state involving the Missouri River. River levels are expected to reach flood stage and preparations are already underway to prevent or minimize damage as a result of the impending flooding. This advisory will primarily affect Woodbury, Monona, Harrison, Pottawattamie, Mills and Fremont Counties.

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A fundamental tenet of neuroscience is that cortical functional differentiation is related to the cross-areal differences in cyto-, receptor-, and myeloarchitectonics that are observed in ex-vivo preparations. An ongoing challenge is to create noninvasive magnetic resonance (MR) imaging techniques that offer sufficient resolution, tissue contrast, accuracy and precision to allow for characterization of cortical architecture over an entire living human brain. One exciting development is the advent of fast, high-resolution quantitative mapping of basic MR parameters that reflect cortical myeloarchitecture. Here, we outline some of the theoretical and technical advances underlying this technique, particularly in terms of measuring and correcting for transmit and receive radio frequency field inhomogeneities. We also discuss new directions in analytic techniques, including higher resolution reconstructions of the cortical surface. We then discuss two recent applications of this technique. The first compares individual and group myelin maps to functional retinotopic maps in the same individuals, demonstrating a close relationship between functionally and myeloarchitectonically defined areal boundaries (as well as revealing an interesting disparity in a highly studied visual area). The second combines tonotopic and myeloarchitectonic mapping to localize primary auditory areas in individual healthy adults, using a similar strategy as combined electrophysiological and post-mortem myeloarchitectonic studies in non-human primates.

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The reelin gene encodes an extracellular protein that is crucial for neuronal migration in laminated brain regions. To gain insights into the functions of Reelin, we performed high-resolution in situ hybridization analyses to determine the pattern of reelin expression in the developing forebrain of the mouse. We also performed double-labeling studies with several markers, including calcium-binding proteins, GAD65/67, and neuropeptides, to characterize the neuronal subsets that express reelin transcripts. reelinexpression was detected at embryonic day 10 and later in the forebrain, with a distribution that is consistent with the prosomeric model of forebrain regionalization. In the diencephalon, expression was restricted to transverse and longitudinal domains that delineated boundaries between neuromeres. During embryogenesis,reelin was detected in the cerebral cortex in Cajal-Retzius cells but not in the GABAergic neurons of layer I. At prenatal stages, reelin was also expressed in the olfactory bulb, and striatum and in restricted nuclei in the ventral telencephalon, hypothalamus, thalamus, and pretectum. At postnatal stages, reelin transcripts gradually disappeared from Cajal-Retzius cells, at the same time as they appeared in subsets of GABAergic neurons distributed throughout neocortical and hippocampal layers. In other telencephalic and diencephalic regions,reelin expression decreased steadily during the postnatal period. In the adult, there was prominent expression in the olfactory bulb and cerebral cortex, where it was restricted to subsets of GABAergic interneurons that co-expressed calbindin, calretinin, neuropeptide Y, and somatostatin. This complex pattern of cellular and regional expression is consistent with Reelin having multiple roles in brain development and adult brain function.

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The Missouri River floods of 2011 will go down in history as the longest duration flooding event this state has seen to date. The combination of above normal snowfall in the upper Missouri River basin followed by the equivalent of nearly one year’s worth of rainfall in May created an above normal runoff situation which filled the Missouri River and the six main reservoirs within the basin. Compounding this problem was colder than normal temperatures which kept much of the snowpack in the upper basin on the ground longer into the spring, setting the stage for this historic event. The U.S. Army Corps of Engineers (USACE) began increasing the outflow at Gavin’s Point, near Yankton, South Dakota in May. On June 14, 2011, the outflow reached a record rate of over 160,000 cubic feet per second (cfs), over twice the previous record outflow set in 1997. This increased output from Gavin’s Point caused the Missouri River to flow out of its banks covering over 283,000 acres of land in Iowa, forcing hundreds of evacuations, damaging 255,000 acres of cropland and significantly impacting the levee system on the Missouri River basin. Over the course of the summer, approximately 64 miles of primary roads closed due to Missouri River flooding, including 54 miles of Interstate Highway. Many county secondary roads were closed by high water or overburdened due to the numerous detours and road closures in this area. As the Missouri River levels began to increase, municipalities and counties aided by State and Federal agencies began preparing for a sustained flood event. Citizens, businesses, state agencies, local governments and non‐profits made substantial preparations, in some cases expending millions of dollars on emergency protective measures to protect their facilities from the impending flood. Levee monitors detected weak spots in the levee system in all affected counties, with several levees being identified as at risk levees that could potentially fail. Of particular concern was the 28 miles of levees protecting Council Bluffs. Based on this concern, Council Bluffs prepared an evacuation plan for the approximately 30,000 residents that resided in the protected area. On May 25, 2011, Governor Branstad directed the execution of the Iowa Emergency Response Plan in accordance with Section 401 of the Stafford Act. On May 31, 2011, HSEMD Administrator, Brigadier General J. Derek Hill, formally requested the USACE to provide technical assistance and advanced measures for the communities along the Missouri River basin. On June 2, 2011 Governor Branstad issued a State of Iowa Proclamation of Disaster Emergency for Fremont, Harrison, Mills, Monona, Pottawattamie, and Woodbury counties. The length of this flood event created a unique set of challenges for Federal, State and local entities. In many cases, these organizations were conducting response and recovery operations simultaneously. Due to the length of this entire event, the State Emergency Operations Center and the local Emergency Operations Centers remained open for an extended period of time, putting additional strain on many organizations and resources. In response to this disaster, Governor Branstad created the Missouri River Recovery Coordination Task Force to oversee the State’s recovery efforts. The Governor announced the creation of this Task Force on October 17, 2011 and appointed Brigadier General J. Derek Hill, HSEMD Administrator as the chairman. This Task Force would be a temporary group of State agency representatives and interested stakeholders brought together to support the recovery efforts of the Iowa communities impacted by the Missouri River Flood. Collectively, this group would analyze and share damage assessment data, coordinate assistance across various stakeholders, monitor progress, capture best practices and identify lessons learned.

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The electronic and magnetic structures of the LaMnO3 compound have been studied by means of periodic calculations within the framework of spin polarized hybrid density-functional theory. In order to quantify the role of approximations to electronic exchange and correlation three different hybrid functionals have been used which mix nonlocal Fock and local Dirac-Slater exchange. Periodic Hartree-Fock results are also reported for comparative purposes. The A-antiferromagnetic ground state is properly predicted by all methods including Hartree-Fock exchange. In general, the different hybrid methods provide a rather accurate description of the band gap and of the two magnetic coupling constants, strongly suggesting that the corresponding description of the electronic structure is also accurate. An important conclusion emerging from this study is that the nature of the occupied states near the Fermi level is intermediate between the Hartree-Fock and local density approximation descriptions with a comparable participation of both Mn and O states.

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The central structure of the symbiotic association between plants and arbuscular mycorrhizal (AM) fungi is the fungal arbuscule that delivers minerals to the plant. Our earlier transcriptome analyses identified two half-size ABCG transporters that displayed enhanced mRNA levels in mycorrhizal roots. We now show specific transcript accumulation in arbusculated cells of both genes during symbiosis. Presently, arbuscule-relevant factors from monocotyledons have not been reported. Mutation of either of the Oryza sativa (rice) ABCG transporters blocked arbuscule growth of different AM fungi at a small and stunted stage, recapitulating the phenotype of Medicago truncatula stunted arbuscule 1 and 2 (str1 and str2) mutants that are deficient in homologous ABCG genes. This phenotypic resemblance and phylogenetic analysis suggest functional conservation of STR1 and STR2 across the angiosperms. Malnutrition of the fungus underlying limited arbuscular growth was excluded by the absence of complementation of the str1 phenotype by wild-type nurse plants. Furthermore, plant AM signaling was found to be intact, as arbuscule-induced marker transcript accumulation was not affected in str1 mutants. Strigolactones have previously been hypothesized to operate as intracellular hyphal branching signals and possible substrates of STR1 and STR2. However, full arbuscule development in the strigolactone biosynthesis mutants d10 and d17 suggested strigolactones to be unlikely substrates of STR1/STR2. Interestingly, rice STR1 is associated with a cis-natural antisense transcript (antiSTR1). Analogous to STR1 and STR2, at the root cortex level, the antiSTR1 transcript is specifically detected in arbusculated cells, suggesting unexpected modes of STR1 regulation in rice.

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Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFalpha levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders.

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Background: BK virus associated nephropathy occurs in 1-10% of kidney transplant recipients and may be a cause of graft loss. This infection is difficult to manage because of the absence of specific therapy. Cidofovir, a DNA polymerase inhibitor approved for the treatment of CMV retinitis, has shown in vitro activity against BK virus and some clinical efficacy when used at low-dose in uncontrolled series. Objective: To assess the efficacy of low-dose Cidofovir in the treatment of BK virus associated nephropathy. Method: Two adult kidney transplant recipients with biopsy-proven BK nephropathy and persistent high viremia (>10,000 copies/ml) despite 3-month reduction of immunosuppressive therapy were treated by Cidofovir 0.5 mg/kg fortnightly for a total of 16 weeks (8 doses). Clinical response was assessed by following BK viremia. Results: No decrease in BK viremia was observed at any point during cidofovir therapy (see figure). Creatinine clearance remained stable during therapy and no side-effects of Cidofovir were observed. Conclusions: Low-dose Cidofovir therapy was not associated with a clearance or with a significant decrease of BK viremia. This pilot study does not confirm previous reports suggesting clinical efficacy of Cidofovir for BK virus associated nephropathy.

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During adolescence numerous of important social abilities are acquired within interactions with peers. Severe psychiatric disorders interfere with the acquisition of these social skills. For example, due to excessive shyness, adolescents with psychiatric disorders may not experiment positive social interactions. Social skills training (SKT) may help adolescents to remediate to these diffi culties. This exploratory study aims to assess the SKT's effect on assertivity, in a population of adolescents presenting psychiatric disorder and attending a day care unit for adolescents. The SKT, delivered in group, deals with different themes such as contact, conversation, problem solving, confl ict, fail, success, learning, effort, separation, breakdown, and project. In this context, 38 adolescents (19 suffering from anxiety / mood disorder and 19 suffering from psychotic disorder) rate their level of assertivity before and after a SKT with the Rathus assertivity scale. This scale allows to differentiate between inhibited, assertive and assertiveaggressive adolescents. Results showed a general improvement on assertivity after the SKT. More specifi cally, adolescents suffering from anxiety disorder and the 'inhibited' adolescents showed the higher benefi t from the SKT. Thus, two hours per week of SKT seems to enhance social abilities in a population with severe psychiatric disorders. More specifi - cally, adolescents with anxiety / mood disorders reported more benefi ts of the SKT on their assertivity. Nevertheless, adolescents with psychotic disorders did not report strong benefi ts from the SKT despite the improvement observed at a clinical level. This observation raises questions about the usefulness of self-reported questionnaire to measure such benefi t for adolescents with psychosis.