1000 resultados para substitution strategies


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The precise sampling of soil, biological or micro climatic attributes in tropical forests, which are characterized by a high diversity of species and complex spatial variability, is a difficult task. We found few basic studies to guide sampling procedures. The objective of this study was to define a sampling strategy and data analysis for some parameters frequently used in nutrient cycling studies, i. e., litter amount, total nutrient amounts in litter and its composition (Ca, Mg, Κ, Ν and P), and soil attributes at three depths (organic matter, Ρ content, cation exchange capacity and base saturation). A natural remnant forest in the West of São Paulo State (Brazil) was selected as study area and samples were collected in July, 1989. The total amount of litter and its total nutrient amounts had a high spatial independent variance. Conversely, the variance of litter composition was lower and the spatial dependency was peculiar to each nutrient. The sampling strategy for the estimation of litter amounts and the amount of nutrient in litter should be different than the sampling strategy for nutrient composition. For the estimation of litter amounts and the amount of nutrients in litter (related to quantity) a large number of randomly distributed determinations are needed. Otherwise, for the estimation of litter nutrient composition (related to quality) a smaller amount of spatially located samples should be analyzed. The determination of sampling for soil attributes differed according to the depth. Overall, surface samples (0-5 cm) showed high short distance spatial dependent variance, whereas, subsurface samples exhibited spatial dependency in longer distances. Short transects with sampling interval of 5-10 m are recommended for surface sampling. Subsurface samples must also be spatially located, but with transects or grids with longer distances between sampling points over the entire area. Composite soil samples would not provide a complete understanding of the relation between soil properties and surface dynamic processes or landscape aspects. Precise distribution of Ρ was difficult to estimate.

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Aquest treball fa un repàs a les diferents teories relacionades amb el camp d’estudi de les estratègies d’aprenentatge de segones llengües i respon a preguntes de recerca relacionades amb la freqüència d’ús de les estratègies i la relació amb les diferències individuals. La primera part és una introducció on s’hi plantegen les preguntes de recerca en les quals es basa el treball. La segona part, consisteix en un resum de les teories relacionades amb el tema de les estratègies d’estudi de segones llengües, i una posada en comú d’aquestes per mostrar les dificultats que hi ha per trobar consens en quant a la identificació i classificació de les estratègies. La tercera part, presenta la metodologia utilitzada per a la recollida de dades per tal de contestar les preguntes de recerca. En la quarta part es desenvolupa la recerca duta a terme; i finalment es presenten les conclusions extretes de cada pregunta de recerca plantejada.

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Resistance to alkylating agents via direct DNA repair by O(6)-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O(6)-benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.

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Understanding factors that shape ranges of species is central in evolutionary biology. Species distribution models have become important tools to test biogeographical, ecological and evolutionary hypotheses. Moreover, from an ecological and evolutionary perspective, these models help to elucidate the spatial strategies of species at a regional scale. We modelled species distributions of two phylogenetically, geographically and ecologically close Tupinambis species (Teiidae) that occupy the southernmost area of the genus distribution in South America. We hypothesized that similarities between these species might have induced spatial strategies at the species level, such as niche differentiation and divergence of distribution patterns at a regional scale. Using logistic regression and MaxEnt we obtained species distribution models that revealed interspecific differences in habitat requirements, such as environmental temperature, precipitation and altitude. Moreover, the models obtained suggest that although the ecological niches of Tupinambis merianae and T. rufescens are different, these species might co-occur in a large contact zone. We propose that niche plasticity could be the mechanism enabling their co-occurrence. Therefore, the approach used here allowed us to understand the spatial strategies of two Tupinambis lizards at a regional scale.

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We report the study of a large American family displaying autosomal dominant retinitis pigmentosa with reduced penetrance, a form of hereditary retinal degeneration. Although the inheritance pattern and previous linkage mapping pointed to the involvement of the PRPF31 gene, extensive screening of all its exons and their boundaries failed in the past to reveal any mutation. In this work, we sequenced the entire PRPF31 genomic region by both the classical Sanger method and ultrahigh throughput (UHT) sequencing. Among the many variants identified, a single-base substitution (c.1374+654C>G) located deep within intron 13 and inside a repetitive DNA element was common to all patients and obligate asymptomatic carriers. This change created a new splice donor site leading to the synthesis of two mutant PRPF31 isoforms, degraded by nonsense-mediated mRNA decay. As a consequence, amounts of PRPF31 mRNA derived from the mutant allele were very reduced, with no evidence of mutant proteins being synthesized. Our results indicate that c.1374+654C>G causes retinitis pigmentosa via haploinsufficiency, similar to the vast majority of PRPF31 mutations described so far. We discuss the potential of UHT sequencing technologies in mutation screening and the continued identification of pathogenic splicing mutations buried deep within intronic regions.

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Essential hypertension is a very heterogeneous disease. The availability of antihypertensive drugs lowering blood pressure by various mechanisms allows most often to tailor the treatment, i.e. to find for each patient a drug regimen that is both efficient and well tolerated. Frequently medications given as monotherapy are not effective enough so that the use of drug combinations is required. When combined, low doses of antihypertensive agents are generally sufficient, so that tolerability is optimally preserved. Unfortunately many patients do not have their blood pressure controlled during antihypertensive therapy. These patients therefore do not benefit maximally from the cardiovascular protection afforded by blood pressure lowering. It is also imperative to correct all cardiovascular risk factors in each hypertensive patient. Such a multifactorial approach is known to improve effectively the prevention of cardiovascular diseases.

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L’èxit de l’iniciativa ciutadana europea (ICE) com a instrument de democràcia directa a nivell europeu està directament relacionat amb la seva promulgació. Els ciutadans d’arreu Europa han d’estar informats sobre aquest nou mecanisme per tal que es dugui a terme, la qual cosa suposa una dificultat. Aquest estudi qualitatiu ens mostra els recursos i problemes en la divulgació de les ICE. Una anàlisi basat en entrevistes amb diferents organitzadors d’aquestes ICE que ens dona algunes idees sobre les seves estratègies de comunicació, així com l’ús d’eines de comunicació i relacions amb els mitjans de comunicació. A banda de les dificultats lingüístiques i financeres hi ha altres obstacles més específics relacionats amb l’ICE.

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L'a. cherche à dater l'historiographie deutéronomiste et à établir une transformation à l'intérieur de cette historiographie. Les écrits de propagande de l'époque de Josias (Rois, Deutéronome, Josué, Exode et Nombres) ont été changés après la catastrophe de 597/87 en récit historique prenant une distance et présentant la Tora prenant la relève de l'autorité perdue du Temple. L'A. peut ainsi pencher pour une rédaction de ce courant historiographique datant de l'époque post-éxilique.

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Advances in the management of non-small cell lung cancer (NSCLC) over the past 30 years have led to small increases in 5-year survival rates across Europe, though further improvements may require new treatment strategies. In order to improve efficiency and reduce the cost of development, future trials for new targeted agents in NSCLC should aim to recruit patients on the basis of tumour biology rather than clinical characteristics. However, identification of predictive biomarkers is required to maximise the benefits of new approaches and expedite the drug development process. Nevertheless, the NSCLC landscape is changing rapidly, and recent improvements in our understanding of the molecular biology of the disease will help in the identification of novel targeted agents as well as assisting in the development of personalised strategies for the numerous small subsets of defined NSCLC. Progress in imaging and treatment delivery is also likely to improve outcomes for patients with the disease. This article outlines recent progress in the treatment of NSCLC, identifies current challenges and describes proposals for improving the future management of the disease. It is hoped that implementation of some of these strategies will go some way to improving the outlook for patients with NSCLC.

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IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

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Com a resultat de les politiques i estratègies de col·laboració entre la universitat de Vic i de l’hospital i de la voluntat de realitzar activitats formatives conjuntes , s’estableix un línia de treball orientada a l’estudi i anàlisi de la situació logística interna actual del laboratori d’anàlisis clíniques de l’Hospital General de Vic. El treball es centra en el procés intern del laboratori i l’abast de l’estudi es troba limitat a les àrees especifiques d’hematologia i coagulació i bioquímica. D’aquestes dues àrees el treball realitza un estudi exhaustiu del seu procés intern, identifica les seves activitats i la seva metodologia de treball amb l’objectiu d’elaborar el Value Stream Map de cadascuna de les àrees. Les àrees de Microbiologia, Banc de Sang i Urgències resten fora d’aquest estudi exhaustiu tot i que són presents en el treball per la inevitable interacció que tenen en la globalitat del procés. El treball es centra bàsicament en els processos automatitzats tot i que els processos que es duen a terme en el laboratori són tant automatitzats com manuals. També es limita al sistema productiu intern del laboratori tot i la interacció que té aquest sistema intern amb altres centres productius del sistema com ara són els centres d’atenció primària, els diversos hospitals i centres d’atenció sociosanitària. El laboratori es troba immers en el moment de l’elaboració d’aquest treball en un situació de canvi i millora del seus processos interns que consisteixen principalment en la substitució de part la maquinària actual que obliguen a la definició d’un nou layout i d’una nova distribució de la producció a cada màquina. A nivell extern també s’estan produint millores en el sistema informàtic de gestió que afecten a part del seu procés. L’objectiu del treball és donar visibilitat total al procés de logística interna actual del laboratori, identificant clarament com són i quina seqüència tenen els processos logístics interns i els mètodes de treball actuals, tant de recursos màquina com recursos persona, per poder identificar sota una perspectiva de generació de valor, aquells punts concrets de la logística interna que poden ser millorats en quant a eficiència i productivitat amb l’objectiu que un cop identificats es puguin emprendre accions i/o projectes de millora. El treball finalitza amb un anàlisis final del procés logística interna des d’una òptica Lean. Per fer-ho, identifica aquelles activitats que no aporten valor al procés o MUDA i les classifica en set categories i es realitzen diverses propostes de millora com són la implantació d’un flux continu , anivellat i basat en un concepte pull , identifica activitats que poden ser estandarditzades i/o simplificades i proposa modificacions en les infraestructures físiques per donar major visibilitat al procés. L’aspecte humà del procés es planteja des d’un punt de vist de metodologia, formació, comunicació i aplicació de les 5S.

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This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work.

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Hormone replacement therapy (HRT) is an established approach for the treatment and the prevention of osteoporosis. Many studies with bone mineral density as primary outcome have shown significant efficacy. Observational studies have indicated a significant reduction of hip fracture risk in cohorts of women who maintained HRT therapy. The Women's Health Initiative is the first prospective randomised controlled study which showed a positive effect of HRT in terms of reduction of vertebral and hip fractures risk. Unfortunately, this study has been interrupted after 5.2 years because of the unsupportable increase of risk of cardiovascular disease and breast cancer. Compliance with HRT, however, is typically poor because of the potential side effects and possible increased risk of breast or endometrial cancer. Nevertheless, there is now evidence that lower doses of estrogens in elderly women may prevent bone loss while minimizing the side effects seen with higher doses. Combination therapies using low doses estrogen should probably be reserved for patients who continue to fracture on single therapy. Selective estrogen receptor modulators (SERMs) are very interesting drugs. The goal of these agents is to maximize the beneficial effect of estrogen on bone and to minimize or antagonize the deleterious effects on the breast and endometrium. Raloxifene, approved for the prevention and the treatment of osteoporosis, has been shown to reduce the risks of vertebral fracture in large clinical trials. However, they don't reduce non vertebral fractures. Tibolone is a synthetic steroid that increased bone mineral density at lumbar spine and femoral neck. But no trial has been performed with fractures as end point.

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Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients.It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.