969 resultados para Ongoing concessions


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Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.

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The recent strides of democracy in Latin America have been associated to conflicting outcomes. The expectation that democracy would bring about peace and prosperity have been only partly satisfied. While political violence has been by and large eradicated from the sub-continent, poverty and social injustice still prevail and hold sway. Our study argues that democracy matters for inequality through the growing strength of center left and left parties and by making political leaders in general more responsive to the underprivileged. Furthermore, although the pension reforms recently enacted in the region generated overall regressive outcomes on income distribution, democratic countries still benefit from their political past: where democratic tradition was stronger, such outcomes have been milder. Democratic tradition and the specific ideological connotations of the parties in power, on the other hand, did not play an equally crucial role in securing lower levels of political violence: during the last wave of democratizations in Latin America, domestic peace was rather an outcome of political and social concessions to those in distress. In sum, together with other factors and especially economic ones, the reason why recent democratizations have provided domestic peace in most cases, but have been unable so far to solve the problem of poverty and inequality, is that democratic traditions in the subcontinent have been relatively weak and, more specifically, that this weakness has undermined the growth of left and progressive parties, acting as an obstacle to redistribution. Such weakness, on the other hand, has not prevented the drastic reduction of domestic political violence, since what mattered in this case was a combination of symbolic or material concessions and political agreements among powerful élites and counter-élites.

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BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

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The relationship between infrastructures and productivity has been the subject of an ongoing debate during the last two decades. The available empirical evidence is inconclusive and its interpretation is complicated by econometric problems that have not been fully solved. This paper surveys the relevant literature, focusing on studies that estimate aggregate production functions or growth regressions, and extracts some tentative conclusions. On the whole, my reading of the evidence is that there are sufficient indications that public infrastructure investment contributes significantly to productivity growth, at least for countries where a saturation point has not been reached. The returns to such investment are probably quite high in early stages, when infrastructures are scarce and basic networks have not been completed, but fall sharply thereafter. Hence, appropriate infrastructure provision is probably a key input for development policy, even if it does not hold the key to rapid productivity growth in advanced countries where transportation and communications needs are already adequately served.

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In ongoing studies on experimental transmission of Plasmodium falciparum in the city of Yaounde gametocyte carriers are daily being identified among dispensary patients with malaria-like complaints. This species comprises 93 of all parasitemias and because of the selection criteria most patients have it as a recent infection. 17 of all P. falciparum-positives carry detectable gametocytes with little difference between youngsters and adults. Blood of adult carriers is taken and infection of Anopheles gambiae mosquitoes is attempted by membrane feeding; the establishment of infection is judged by the presence of oocysts.

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Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

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Sampling issues represent a topic of ongoing interest to the forensic science community essentially because of their crucial role in laboratory planning and working protocols. For this purpose, forensic literature described thorough (Bayesian) probabilistic sampling approaches. These are now widely implemented in practice. They allow, for instance, to obtain probability statements that parameters of interest (e.g., the proportion of a seizure of items that present particular features, such as an illegal substance) satisfy particular criteria (e.g., a threshold or an otherwise limiting value). Currently, there are many approaches that allow one to derive probability statements relating to a population proportion, but questions on how a forensic decision maker - typically a client of a forensic examination or a scientist acting on behalf of a client - ought actually to decide about a proportion or a sample size, remained largely unexplored to date. The research presented here intends to address methodology from decision theory that may help to cope usefully with the wide range of sampling issues typically encountered in forensic science applications. The procedures explored in this paper enable scientists to address a variety of concepts such as the (net) value of sample information, the (expected) value of sample information or the (expected) decision loss. All of these aspects directly relate to questions that are regularly encountered in casework. Besides probability theory and Bayesian inference, the proposed approach requires some additional elements from decision theory that may increase the efforts needed for practical implementation. In view of this challenge, the present paper will emphasise the merits of graphical modelling concepts, such as decision trees and Bayesian decision networks. These can support forensic scientists in applying the methodology in practice. How this may be achieved is illustrated with several examples. The graphical devices invoked here also serve the purpose of supporting the discussion of the similarities, differences and complementary aspects of existing Bayesian probabilistic sampling criteria and the decision-theoretic approach proposed throughout this paper.

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Approximately 50 publications have become available in the international literature on ultrasonography in schistosomiasis in Africa. Geographically these cover Congo, Egypt, Kenya, Mali, Mauritius, Niger, Senegal, Sudan, Tanzania and East African Islands as well as Zimbabwe. Further studies are ongoing in many countries, such as Burundi, Ghana, Madagaskar and Uganda. It was shown that ultrasonography is useful in the detection of morbidity induced by schistosomiasis on an individual basis and on the community level. There is indication for varying morbidity patterns in different African foci. Post-treatment monitoring has provided evidence for reversibility of pathological lesions induced by Schistosoma (S.) haematobium and S. mansoni, even though evidence for reversibility of periportal fibrosis in adults is not yet satisfactorily substantiated. A standardized set of criteria for ultrasonographical observations has been worked out and is presently in the process of being refined. It is thus hoped that standardization will contribute to render studies in different endemic settings comparable on a global basis.

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The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.

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En este trabajo se exploran los condicionantes sociológicos e institucionales del mercado del servicio doméstico en Europa. Para ello se trabajó, básicamente, en tres líneas de investigación que aun están en curso. La primera, consiste en una exploración filosófica republicana, histórica y jurídica de la familia y la empresa capitalistas como instituciones que tienen una raigambre histórica común –la antigua domus, donde se desarrollaban todas las actividades productivas y reproductivas y que se caracterizaba constitutivamente por relaciones de dominación entre el propietario de los medios de producción y todos aquéllos que dependían de éste para subsistir-. Bajo el capitalismo, la familia –entendida ya como el hombre, su mujer e hijos legítimos- se constituyó en una institución eminentemente privada y las actividades desarrolladas en su seno quedaron fuera de lo que se consideró trabajo susceptible de reconocimiento económico. En este sentido, la normativa que regula al servicio doméstico como una relación laboral de carácter “especial” es un reflejo de la desvalorización socioeconómica de que ha sido objeto el trabajo reproductivo y la asociación conceptual entre la “improductividad” del ama de casa y la empleada doméstica. En la segunda línea del trabajo se exploraron las variaciones cuantitativas del mercado del servicio doméstico en Europa, cuya trayectoria presenta una forma de U entre la década de 1880 y mediados de la década de 1990. También mediante el análisis de fuentes secundarias de datos se pudieron establecer las profundas diferencias regionales que ha comportado este resurgimiento del empleo en servicios domésticos y su peso dentro de la estructura de empleo de cada sociedad. Por último, en la tercera se indagó la fluctuación histórica y geográfica de la oferta de trabajadoras domésticas en Europa, que pasó de las migraciones internas a las internacionales, coincidiendo con periodos de fuerte desigualdad económica entre las zonas expulsoras y receptoras.

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Malonate, methylmalonate and propionate are potentially neurotoxic metabolites in branched-chain organic acidurias. Their effects were tested on cultured 3D rat brain cell aggregates, using dosages of 0.1, 1.0 and 10.0 mM with a short but intense (twice a day over 3 days) and a longer but less intense treatment (every 3 rdday over 9 days). CNS cell-specific immunohistochemical stainings allowed the follow-up of neurons (axons, phosphorylated medium-weight neurofilament), astrocytes (glial fibrillary acidic protein) and oligodendrocytes (myelin basic protein). Methylmalonate and malonate were quantified by tandem mass spectrometry. Tandem mass spectrometry analysis of harvested brain cell aggregates revealed clear intracellular accumulation of methylmalonate and malonate. In immunohistochemical stainings oligodendrocytes appeared the most affected brain cells. The MBP signal disappeared already at 0.1 mM treatment with each metabolite. Mature astrocytes were not affected by propionate, while immature astrocytes on intense treatment with propionate developed cell swelling. 1 mM methylmalonate induced cell swelling of both immature and mature astrocytes , while 1 mM malonate only affected mature astrocytes. Neurons were not affected by methylmalonate, but 10.0 mM malonate on less intense treatment and 0.1, 1.0 and 10.0 mM propionate on intense treatment affected axonal growth. Our study shows significant uptake and deleterious effects of these metabolites on brain cells, principally on astrocytes and oligodendrocytes. This may be explained by the absence of the pathway in glial cells, which thus are not able to degrade these metabolites. Further studies are ongoing to elucidate the underlying mechanisms of the observed neurotoxic effects.

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The Cinque Torri group (Cortina d'Ampezzo, Italy) is an articulated system of unstable carbonatic rock monoliths located in a very important tourism area and therefore characterized by a significant risk. The instability phenomena involved represent an example of lateral spreading developed over a larger deep seated gravitational slope deformation (DSGSD) area. After the recent fall of a monolith of more than 10 000 m3, a scientific study was initiated to monitor the more unstable sectors and to characterize the past movements as a fundamental tool for predicting future movements and hazard assessment. To achieve greater insight on the ongoing lateral spreading process, a method for a quantitative analysis of rotational movements associated with the lateral spreading has been developed, applied and validated. The method is based on: i) detailed geometrical characterization of the area by means of laser scanner techniques; ii) recognition of the discontinuity sets and definition of a reference frame for each set, iii) correlation between the obtained reference frames related to a specific sector and a stable external reference frame, and iv) determination of the 3D rotations in terms of Euler angles to describe the present settlement of the Cinque Torri system with respect to the surrounding stable areas. In this way, significant information on the processes involved in the fragmentation and spreading of a former dolomitic plateau into different rock cliffs has been gained. The method is suitable to be applied to similar case studies.

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En el projecte Ampliació i millora d’un vehicle teledirigit s’ha dut a terme l’ampliació d’un prototip de vehicle ràdio controlat fent servir dues plaques Arduino Duemilanove. Una es situa en el comandament i l’altra en el vehicle i controlen el comportament dels dos dispositius. Es transmet la informació necessària entre elles a través de dos mòduls XBee que posteriorment se’ls hi incorpora. Les plaques fetes servir en el prototip inicial eren unes SARD-13192 de Freescale i el primer que es fa en aquest sentit és una revisió del codi font utilitzat i l’adaptació a les plaques Arduino. Un acceleròmetre ADXL335 que s’incorpora a una de les plaques permet que el prototip es pugui controlar segons la posició del comandament. A més, un cop finalitzat el nou prototip és capaç de desplaçar-se endavant i endarrere, girar aturat i en moviment, i a diferents velocitats que es representen en tot moment en uns LEDs. També guarda l’últim circuit efectuat que es pot reproduir a voluntat de l’usuari, i emmagatzema les dades del recorregut de tota una sessió per exportar a l’ordinador. Per últim s’han dut a terme les proves necessàries per constatar que totes les millores s’han implementat amb èxit.

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Glutaryl-CoA dehydrogenase (GCDH, EC 1.3.99.7) deficiency, known as glutaric acidemia type I, is one of the more common organic acidurias. To investigate the role of this pathway in different organs we studied the tissue-specific expression pattern of rat Gcdh. The open reading frame cDNA of the rat Gcdh gene was cloned from rat brain mRNA by RT-PCR, allowing the synthesis of digoxigenin-labeled in situ hybridization (ISH) riboprobes. Gcdh mRNA expression was analyzed by ISH on cryosections of adult rat brain, kidney, liver, spleen and heart muscle, as well as on E15 and E18 rat embryos. Gcdh was found expressed in the whole rat brain, almost exclusively in neurons. Gcdh was absent from astrocytes but expressed in rare oligodendrocytes. Strong Gcdh expression was found in liver and spleen, where expression appears predominant to lymphatic nodules. In kidney, the highest Gcdh expression is found in the juxtamedullar cortex (but not in glomerula), and at lower levels in medulla. Heart muscle was negative. During embryonic development, Gcdh was found well expressed in liver, intestinal mucosa and skin, as well as at lower levels in CNS. Further studies are ongoing to provide evidence on the presence of the entire pathway in CNS in order to understand the mechanisms leading to neurotoxicity in glutaric aciduria. The high expression of Gcdh in kidney may explain why certain patients with residual enzyme activity are low excretors at the urine metabolite level.

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In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.