Showing papers by "State University of Campinas published in 2006"

Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response

Abstract: We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 x 10(12) vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of approximately 8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Abstract: Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.

Abstract: Summary: Purpose: To assess which antiepileptic medications (AEDs) have the best evidence for long-term efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy. Methods: A 10-member subcommission of the Commission on Therapeutic Strategies of The International League Against Epilepsy (ILAE), including adult and pediatric epileptologists, clinical pharmacologists, clinical trialists, and a statistician evaluated available evidence found through a structured literature review including MEDLINE, Current Contents and the Cochrane Library for all applicable articles from 1940 until July 2005. Articles dealing with different seizure types (for different age groups) and two epilepsy syndromes were assessed for quality of evidence (four classes) based on predefined criteria. Criteria for class I classification were a double-blind randomized controlled trial (RCT) design, ≥48-week treatment duration without forced exit criteria, information on ≥24-week seizure freedom data (efficacy) or ≥48-week retention data (effectiveness), demonstration of superiority or 80% power to detect a ≤20% relative difference in efficacy/effectiveness versus an adequate comparator, and appropriate statistical analysis. Class II studies met all class I criteria except for having either treatment duration of 24 to 47 weeks or, for noninferiority analysis, a power to only exclude a 21–30% relative difference. Class III studies included other randomized double-blind and open-label trials, and class IV included other forms of evidence (e.g., expert opinion, case reports). Quality of clinical trial evidence was used to determine the strength of the level of recommendation. Results: A total of 50 RCTs and seven meta-analyses contributed to the analysis. Only four RCTs had class I evidence, whereas two had class II evidence; the remainder were evaluated as class III evidence. Three seizure types had AEDs with level A or level B efficacy and effectiveness evidence as initial monotherapy: adults with partial-onset seizures (level A, carbamazepine and phenytoin; level B, valproic acid), children with partial-onset seizures (level A, oxcarbazepine; level B, None), and elderly adults with partial-onset seizures (level A, gabapentin and lamotrigine; level B, None). One adult seizure type [adults with generalized-onset tonic–clonic (GTC) seizures], two pediatric seizure types (GTC seizures and absence seizures), and two epilepsy syndromes (benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy) had no AEDs with level A or level B efficacy and effectiveness evidence as initial monotherapy. Conclusions: This evidence-based guideline focused on AED efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy. The absence of rigorous comprehensive adverse effects data makes it impossible to develop an evidence-based guideline aimed at identifying the overall optimal recommended initial-monotherapy AED. There is an especially alarming lack of well-designed, properly conducted RCTs for patients with generalized seizures/epilepsies and for children in general. The majority of relevant existing RCTs have significant methodologic problems that limit their applicability to this guideline's clinically relevant main question. Multicenter, multinational efforts are needed to design, conduct and analyze future clinically relevant RCTs that can answer the many outstanding questions identified in this guideline. The ultimate choice of an AED for any individual patient with newly diagnosed or untreated epilepsy should include consideration of the strength of the efficacy and effectiveness evidence for each AED along with other variables such as the AED safety and tolerability profile, pharmacokinetic properties, formulations, and expense. When selecting a patient's AED, physicians and patients should consider all relevant variables and not just efficacy and effectiveness.

Observation of muon neutrino disappearance with the MINOS detectors in the NuMI neutrino beam

Abstract: This letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rate and energy spectra of charged current muon neutrino interactions are compared in two detectors located along the beam axis at distances of 1 km and 735 km. With 1.27 x 10^{20} 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336 \\\\\\\\\\\\\\\\pm 14.4 events. The data are consistent with muon neutrino disappearance via oscillation with |\\\\\\\\\\\\\\\\Delta m^2_{23}| = 2.74^{+0.44}_{-0.26} x 10^{-3} eV^2/c^4 and sin^2(2\\\\\\\\\\\\\\\\theta_{23}) > 0.87 (at 60% C.L.).

The Role of Sucrose in Cariogenic Dental Biofilm Formation—New Insight

Abstract: Dental caries is a biofilm-dependent oral disease, and fermentable dietary carbohydrates are the key environmental factors involved in its initiation and development. However, among the carbohydrates, sucrose is considered the most cariogenic, because, in addition to being fermented by oral bacteria, it is a substrate for the synthesis of extracellular (EPS) and intracellular (IPS) polysaccharides. Therefore, while the low pH environment triggers the shift of the resident plaque microflora to a more cariogenic one, EPS promote changes in the composition of the biofilms’ matrix. Furthermore, it has recently been shown that the biofilm formed in the presence of sucrose presents low concentrations of Ca, Pi, and F, which are critical ions involved in de- and remineralization of enamel and dentin in the oral environment. Thus, the aim of this review is to explore the broad role of sucrose in the cariogenicity of biofilms, and to present a new insight into its influence on the pathogenesis of dental caries.

AtALMT1, which encodes a malate transporter, is identified as one of several genes critical for aluminum tolerance in Arabidopsis

Abstract: Aluminum (Al) tolerance in Arabidopsis is a genetically complex trait, yet it is mediated by a single physiological mechanism based on Al-activated root malate efflux. We investigated a possible molecular determinant for Al tolerance involving a homolog of the wheat Al-activated malate transporter, ALMT1. This gene, named AtALMT1 (At1g08430), was the best candidate from the 14-memberAtALMT family to be involved with Al tolerance based on expression patterns and genomic location. Physiological analysis of a transferred DNA knockout mutant for AtALMT1 as well as electrophysiological examination of the protein expressed in Xenopus oocytes showed that AtALMT1 is critical for Arabidopsis Al tolerance and encodes the Al-activated root malate efflux transporter associated with tolerance. However, gene expression and sequence analysis of AtALMT1 alleles from tolerant Columbia (Col), sensitive Landsberg erecta (Ler), and other ecotypes that varied in Al tolerance suggested that variation observed at AtALMT1 is not correlated with the differences observed in Al tolerance among these ecotypes. Genetic complementation experiments indicated that the Ler allele of AtALMT1 is equally effective as the Col allele in conferring Al tolerance and Al-activated malate release. Finally, fine-scale mapping of a quantitative trait locus (QTL) for Al tolerance on chromosome 1 indicated that AtALMT1 is located proximal to this QTL. These results indicate that AtALMT1 is an essential factor for Al tolerance in Arabidopsis but does not represent the major Al tolerance QTL also found on chromosome 1.

Improving the analyses of nestedness for large sets of matrices

Abstract: Nestedness is a property of binary matrices of ecological data and quantified by the matrix's temperature, T. The program widely used to calculate T is Nestedness Temperature Calculator (NTC). NTC analyses matrices individually, turning the analysis of large sets time-consuming. We introduce ANINHADO, a program developed to perform rapid and automatic calculation of T over 10,000 matrices. ANINHADO can be useful to minimize the time spent in analysis and to compare real data against a variety of null models that typically generate a large number of replicates.

First direct observation of Dirac fermions in graphite

Abstract: Originating from relativistic quantum field theory, Dirac fermions have been invoked recently to explain various peculiar phenomena in condensed-matter physics, including the novel quantum Hall effect in graphene1,2, the magnetic-field-driven metal–insulator-like transition in graphite3,4, superfluidity in 3He (ref. 5) and the exotic pseudogap phase of high-temperature superconductors6,7. Despite their proposed key role in those systems, direct experimental evidence of Dirac fermions has been limited. Here, we report the first direct observation of relativistic Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H, which coexist with quasiparticles that have a parabolic dispersion near another BZ corner K. In addition, we also report a large electron pocket that we attribute to defect-induced localized states. Thus, graphite presents a system in which massless Dirac fermions, quasiparticles with finite effective mass and defect states all contribute to the low-energy electronic dynamics.

Structure in plant–animal interaction assemblages

Abstract: We present a comprehensive approach to detect pattern in assemblages of plant and animal species linked by interactions such as pollination, frugivory or herbivory. Simple structural models produce gradient, compartmented or nested patterns of interaction; intermediate patterns between a gradient and compartments are possible, and nesting within compartments produces a combined model. Interaction patterns can be visualized and analyzed either as matrices, as bipartite networks or as multivariate sets through correspondence analysis. We argue that differences among patterns represent outcomes of distinct evolutionary and ecological processes in these highly diversified assemblages. Instead of choosing one model a priori, assemblages should be probed for a suite of patterns. A plant-pollinator assemblage exemplifies a simple nested pattern, whereas a plant-herbivore assemblage illustrates a compound pattern with nested structures within compartments. Compartmentation should reflect coevolutionary histories and constraints, whereas differences in species abundance or dispersal may generate nestedness.

Stability and stabilization of discrete time switched systems

Abstract: This paper addresses two strategies for stabilization of discrete time linear switched systems. The first one is of open loop nature (trajectory independent) and is based on the determination of an upper bound of the minimum dwell time by means of a family of quadratic Lyapunov functions. The relevant point on dwell time calculation is that the proposed stability condition does not require the Lyapunov function be uniformly decreasing at every switching time. The second one is of closed loop nature (trajectory dependent) and is designed from the solution of what we call Lyapunov–Metzler inequalities from which the stability condition is expressed. Being non-convex, a more conservative but simpler to solve version of the Lyapunov–Metzler inequalities is provided. The theoretical results are illustrated by means of examples.

Guideliness in paracoccidioidomycosis

Abstract: 1.Departamento de Molestias Infecciosas e Parasitarias da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP. 2. Departamento de Saude Comunitaria da Universidade Federal do Parana, Curitiba, PR. 3. Departamento de Doencas Tropicais e Diagnostico por Imagem da Faculdade de Medicina Botucatu da Universidade Estadual de Sao Paulo, Sao Paulo, SP. 4. Departamento de Medicina da Escola Paulista de Medicina, Sao Paulo, SP. 5. Departamento de Clinica Medica da Faculdade Ciencias Medicas da Universidade Estadual de Campinas, Campinas, SP. *Consultores do Consenso em Paracoccidioidomicose: Adriana Kono, Antonia Terezinha Tresoldi, Bodo Wanke, Carlos Roberto Carvalho, Gil Benard, Luiz Carlos Severo, Marcelo Simao Ferreira, Mario Leon Silva Vergara, Roberto Martinez, Rogerio Jesus Pedro, Silvio Alencar Marques, Zarifa Khoury. Patrocinio sem conflito de interesse com entidades privadas: Sociedade Brasileira de Medicina Tropical, Sociedade Brasileira de Infectologia e Sociedade Paulista de Infectologia. Endereco para correspondencia: Dra. Maria Aparecida Shikanai-Yasuda. Laboratorio de Imunologia. Av. Eneias de Carvalho Aguiar 500, Terreo, Sala 4, 05403-000 Sao Paulo, Brasil. Tel: 11 3066-7048, Fax:11 3069-7507 e-mail: lim48imuno@yahoo.com.br Recebido para publicacao em 20/5/2006 Aceito em 2/6/2006 1. INTRODUCAO

Desorption sonic spray ionization for (high) voltage-free ambient mass spectrometry

Abstract: Sonic spray ionization is shown to create a supersonic cloud of charged droplets able to promote efficient desorption and ionization of drugs directly from the surfaces of commercial drug tablets at ambient conditions. Compared with desorption electrospray ionization (DESI), desorption sonic spray ionization (DeSSI) is advantageous since it uses neither heating nor high voltages at the spray capillary. DeSSI therefore provides a more friendly environment in which to perform ambient mass spectrometry (MS). DeSSI-MS is herein evaluated for the analysis of drug tablets, and found to be, in general, as sensitive as DESI-MS. The (high) voltage-free DeSSI method provides, however, cleaner mass spectra with less abundant solvent cluster ions and with enough abundant analyte signal for tandem mass spectrometry (MS/MS). These features may therefore facilitate the DeSSI-MS detection of low molar mass components or impurities, or both. The higher-velocity supersonic DeSSI spray also facilitates matrix penetration thus providing more homogenous sampling and longer lasting ion signals.

Spectral residual method without gradient information for solving large-scale nonlinear systems of equations

Abstract: A fully derivative-free spectral residual method for solving largescale nonlinear systems of equations is presented. It uses in a systematic way the residual vector as a search direction, a spectral steplength that produces a nonmonotone process and a globalization strategy that allows for this nonmonotone behavior. The global convergence analysis of the combined scheme is presented. An extensive set of numerical experiments that indicate that the new combination is competitive and frequently better than well-known Newton-Krylov methods for largescale problems is also presented.

Consenso em paracoccidioidomicose

Abstract: Universidade de Sao Paulo Faculdade de Medicina Departamento de Molestias Infecciosas e Parasitarias

Stimulated Brillouin scattering from multi-GHz-guided acoustic phonons in nanostructured photonic crystal fibres

Abstract: Wavelength-scale periodic microstructuring dramatically alters the optical properties of materials. An example is glass photonic crystal fibre1 (PCF), which guides light by means of a lattice of hollow micro/nanochannels running axially along its length. In this letter, we explore stimulated Brillouin scattering in PCFs with subwavelength-scale solid silica glass cores. The large refractive-index difference between air and glass allows much tighter confinement of light than is possible in all-solid single-mode glass optical fibres made using conventional techniques. When the silica-air PCF has a core diameter of around 70% of the vacuum wavelength of the launched laser light, we find that the spontaneous Brillouin signal develops a highly unusual multi-peaked spectrum with Stokes frequency shifts in the 10-GHz range. We attribute these peaks to several families of guided acoustic modes each with different proportions of longitudinal and shear strain, strongly localized to the core2,3. At the same time, the threshold power for stimulated Brillouin scattering4 increases fivefold. The results show that Brillouin scattering is strongly affected by nanoscale microstructuring, opening new opportunities for controlling light—sound interactions in optical fibres.

Microstructured-core optical fibre for evanescent sensing applications.

Abstract: The development of microstructured fibres offers the prospect of improved fibre sensing for low refractive index materials such as liquids and gases. A number of approaches are possible. Here we present a new approach to evanescent field sensing, in which both core and cladding are microstructured. The fibre was fabricated and tested, and simulations and experimental results are shown in the visible region to demonstrate the utility of this approach for sensing.

Photosensitization of in vitro biofilms by toluidine blue O combined with a light-emitting diode

Abstract: the viability of 5-d biofilms. Both the number of micro-organisms and the concentration of water-insoluble polysaccharide increased with the age of the biofilms. A significant reduction (� 95%) in viability was observed for S. mutans and S. sobrinus biofilms following photosensitization, with a > 99.9% reduction in the viability of S. sanguinis biofilms. In conclusion, a biofilm model was shown to be suitable for studying changes in bacterial numbers and enamel mineralization and for demonstrating the potential value of photosensitization in the control of in vitro biofilms.

Desigualdades sociais na prevalência de doenças crônicas no Brasil, PNAD-2003

Abstract: Os inqueritos de saude de base populacional constituem o principal instrumento utilizado para conhecer a prevalencia de doencas cronicas, de restricoes de atividades e de uso de servicos de saude. Com base nos dados da PNAD-2003, foram estimadas as prevalencias das 12 doencas cronicas pesquisadas, segundo sexo, idade, cor, escolaridade, macrorregiao de residencia e situacao urbana ou rural do domicilio. Foram analisados a presenca de limitacoes e o uso de servicos de saude segundo a presenca de doenca cronica. Utilizando regressao de Poisson, foram estimadas as razoes de prevalencias ajustadas por idade, sexo, macrorregiao de residencia e tipo de respondente. A prevalencia de pelo menos uma doenca cronica aumentou com a idade, foi maior entre mulheres, indigenas, pessoas com menor escolaridade, cidadaos detentores de plano de saude, migrantes de outros estados, residentes em areas urbanas e moradores da regiao Sul. A presenca de doenca cronica provocou aumento de limitacao de atividades e da demanda por servicos de saude. As condicoes mais prevalentes foram: doenca de coluna, hipertensao, artrite e depressao. Foi detectada significativa desigualdade social no padrao das doencas cronicas, segundo genero, cor/raca, nivel de escolaridade, regiao de residencia e situacao do domicilio.