The Brazilian electronic theses and dissertations digital library: providing open access for scholarly information

This paper describes a project led by the Instituto Brasileiro de Informações em Ciência e Tecnologia (Ibict), a government institution, to build a national digital library for electronic theses and dissertations - Bibliteca Digital de Teses e Dissertações (BDTD). The project has been a collaborative effort among Ibict, universities and other research centers in Brazil. The developers adopted a system architecture based on the Open Archives Initiative (OAI) in which universities and research centers act as data providers and Ibict as a service provider. A Brazilian metadata standard for electronic theses and dissertations was developed for the digital library. A toolkit including open source package was also developed by Ibict to be distributed to potential data providers. BDTD has been integrated with the international initiative: the Networked Digital Library of Thesis and Dissertation (NDLTD). Discussions in the paper address various issues related to project design, development and management as well as the role played by Ibict. Conclusions highlight some important lessons learned to date and challenges for the future in expanding the BDTD project.

Evolution of gene expression in fire ants: the effects of developmental stage, caste, and species.

Ants provide remarkable examples of equivalent genotypes developing into divergent and discrete phenotypes. Diploid eggs can develop either into queens, which specialize in reproduction, or workers, which participate in cooperative tasks such as building the nest, collecting food, and rearing the young. In contrast, the differentiation between males and females generally depends upon whether eggs are fertilized, with fertilized (diploid) eggs giving rise to females and unfertilized (haploid) eggs giving rise to males. To obtain a comprehensive picture of the relative contributions of gender (sex), caste, developmental stage, and species divergence to gene expression evolution, we investigated gene expression patterns in pupal and adult queens, workers, and males of two species of fire ants, Solenopsis invicta and S. richteri. Microarray hybridizations revealed that variation in gene expression profiles is influenced more by developmental stage than by caste membership, sex, or species identity. The second major contributor to variation in gene expression was the combination of sex and caste. Although workers and queens share equivalent diploid nuclear genomes, they have highly distinctive patterns of gene expression in both the pupal and the adult stages, as might be expected given their extraordinary level of phenotypic differentiation. Overall, the difference in the proportion of differentially expressed genes was greater between workers and males than between workers and queens or queens and males, consistent with the fact that workers and males share neither gender nor reproductive capability. Moreover, between-species comparisons revealed that the greatest difference in gene expression patterns occurred in adult workers, a finding consistent with the fact that adult workers most directly experience the distinct external environments characterizing the different habitats occupied by the two species. Thus, much of the evolution of gene expression in ants may occur in the worker caste, despite the fact that these individuals are largely or completely sterile. Analyses of gene expression evolution revealed a combination of positive selection and relaxation of stabilizing selection as important factors driving the evolution of such genes.

HDR brachytherapy boost and external radiotherapy for unfavorable prostate cancer patients

Purpose/Objective: To evaluate the outcome of prostate cancer patients treated with a combination of HDR Brachytherapy boost (HDR-BT) and 3D conformal external pelvic radiotherapy (EBRT) in a dose escalation study. Materials and Methods: 162 patients were followed between November 2004 and December 2010 . Two different dose escalation groups were done: group 1 (n= 92), 1 fraction HDR boost (9-10 Gy ) followed by EBRT (60 Gy in 6 weeks) - BED: 203-216 Gy and group 2 (n=70): 2 fraction HDR boost (18-19 Gy), 6 hours interval between fractions, followed by EBRT (46 Gy in 4.5 weeks) - BED: 233.3 -247 Gy; 116 pts (71.6%) received concomitant androgen deprivation. Patients were classified according to the MSKCC criteria into high (N=137) and intermediate (N=25) risk. Phoenix biochemical failure definition was used. Toxicity was scored by Radiation Morbidity Scoring Criteria (RTOG) Results: The mean follow-up was 41 (range 7-84) months. The 7- years cancer-specific and overall survival was 100% an 92%, respectively. The 7 years actuarial biochemical control rate was 89% and 100% for group 1 and 2, respectively. One patient from group 1 and two patients from group 2 never reached a low nadir. Two patients developed distant metastases 12 and 16 months after the treatment. In a multivariate Cox-regression analysis neither treatment nor risk group (intermediate vs. high risk) were associated with increased risk for biochemical failure. The RTOG grade 3 genitourinary early toxicity was 1.0% and 8.5% while gastrointestinal/genitourinary late toxicity was 7.6% and 1.4% for group 1 and 2, respectively Conclusions: HDR BT boost followed by EBRT appears to be a safe, feasible and effective treatment for patients with unfavorable localized prostate cancer. This study shows a beneficial effect on biochemical control in group 2 pts, however without statistical significance. Higher radiation doses (BED 233.3-247 Gy) do not seem to carry extra toxicity.

Combination of androgen deprivation therapy and radiotherapy for localized prostate cancer in the contemporary era.

Currently, androgen deprivation therapy (ADT) has a well-defined role when administered together with radiotherapy (RT): neo-adjuvant and concurrent combination for intermediate risk-disease and adjuvant therapy for high risk disease. Evidence of this association was generated by randomized trials designed and led approximately 30 years ago; thus the question which arises is how relevant and portable are these data in our current clinical practice? In the present review, we examine the pitfalls of these published randomized controlled trials, their relevance to present daily clinics, where high-dose external beam RT or brachytherapy is applied, as well as the adoption of ADT in patients with concomitant cardiovascular disorders.

Electronic Bulletin Board System, HR-345, 1998

The primary objectives of the Electronic Bulletin Board System (BBS) project were to: (1) Provide an electronic communication tool which would link city and county engineering offices to each other and to other governmental agencies for messaging and data sharing; (2) Provide a dial-up site for reference information or files accessible on-demand; and (3) Provide a "stepping stone" to the world of electronic data transfer, recognizing that most local government employees face a huge complex of technology with limited knowledge of computers and communications tools. The system was designed to be as simple as possible, and to require minimal equipment and software cost to the users. The original system was an Apex 386/25 computer with MS-DOS 5.0 software and the final configuration was an HP Vectra XM Pentium 90 with MS-NT 3.51 and Mustang - Wildcat 5.0 software. The users of the BBS were county engineers and their staff, offices in the central office of the Iowa Department of Transportation (DOT) and Resident Construction Engineers at the Iowa DOT. Much of the activity was between the county engineers, and their staffs, and the Iowa DOT offices with which they have ongoing business activities. The BBS contained files for mapping, Internet e-mail service, Accident Location Analysis System (ALAS) data, Iowa DOT bid lettings, and Autocad and Intergraph maps and standards. The 800 line calls were recorded and gave the best indication of the usage and the trends that were being followed. The usage tended to be higher in the winter months when design activities are occurring and lower in the summer months when the construction is in progress. The project was judged a success. The BBS did provide a "stepping stone" to the world of electronic data transfer.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Development and validation of a clinical prediction rule for chest wall syndrome in primary care.

ABSTRACT: BACKGROUND: Chest wall syndrome (CWS), the main cause of chest pain in primary care practice, is most often an exclusion diagnosis. We developed and evaluated a clinical prediction rule for CWS. METHODS: Data from a multicenter clinical cohort of consecutive primary care patients with chest pain were used (59 general practitioners, 672 patients). A final diagnosis was determined after 12 months of follow-up. We used the literature and bivariate analyses to identify candidate predictors, and multivariate logistic regression was used to develop a clinical prediction rule for CWS. We used data from a German cohort (n = 1212) for external validation. RESULTS: From bivariate analyses, we identified six variables characterizing CWS: thoracic pain (neither retrosternal nor oppressive), stabbing, well localized pain, no history of coronary heart disease, absence of general practitioner's concern, and pain reproducible by palpation. This last variable accounted for 2 points in the clinical prediction rule, the others for 1 point each; the total score ranged from 0 to 7 points. The area under the receiver operating characteristic (ROC) curve was 0.80 (95% confidence interval 0.76-0.83) in the derivation cohort (specificity: 89%; sensitivity: 45%; cut-off set at 6 points). Among all patients presenting CWS (n = 284), 71% (n = 201) had a pain reproducible by palpation and 45% (n = 127) were correctly diagnosed. For a subset (n = 43) of these correctly classified CWS patients, 65 additional investigations (30 electrocardiograms, 16 thoracic radiographies, 10 laboratory tests, eight specialist referrals, one thoracic computed tomography) had been performed to achieve diagnosis. False positives (n = 41) included three patients with stable angina (1.8% of all positives). External validation revealed the ROC curve to be 0.76 (95% confidence interval 0.73-0.79) with a sensitivity of 22% and a specificity of 93%. CONCLUSIONS: This CWS score offers a useful complement to the usual CWS exclusion diagnosing process. Indeed, for the 127 patients presenting CWS and correctly classified by our clinical prediction rule, 65 additional tests and exams could have been avoided. However, the reproduction of chest pain by palpation, the most important characteristic to diagnose CWS, is not pathognomonic.

The ciliary smooth muscle electrotransfer: basic principles and potential for sustained intraocular production of therapeutic proteins.

BACKGROUND: We have developed a nonviral gene therapy method based on the electrotransfer of plasmid in the ciliary muscle. These easily accessible smooth muscle cells could be turned into a biofactory for any therapeutic proteins to be secreted in a sustained manner in the ocular media. METHODS: Electrical conditions, design of electrodes, plasmid formulation, method and number of injections were optimized in vivo in the rat by localizing β-galactosidase expression and quantifying reporter (luciferase) and therapeutic (anti-tumor necrosis factor) proteins secretion in the ocular media. Anatomical measurements were performed via human magnetic resonance imaging to design a human eye-sized prototype that was tested in the rabbit. RESULTS: In the rat, transscleral injection of 30 µg of plasmid diluted in half saline (77 mM NaCl) followed by application of eight square-wave electrical pulses (15 V, 10 ms, 5.3 Hz) using two platinum/iridium electrodes, an internal wire and an external sheet, delivered plasmid efficiently to the ciliary muscle fibers. Gene transfer resulted in a long-lasting (at least 5 months) and plasmid dose-/injection number- dependent secretion of different molecular weight proteins mainly in the vitreous, without any systemic exposure. Because ciliary muscle anatomical measurements remained constant among ages in adult humans, an integrated device comprising needle-electrodes was designed and manufactured. Its usefulness was validated in the rabbit. CONCLUSIONS: Plasmid electrotransfer to the ciliary muscle with a suitable medical device represents a promising local and sustained protein delivery system for treating posterior segment diseases, avoiding repeated intraocular injections.

An integer-based score to predict functional outcome in acute ischemic stroke: The ASTRAL score.

OBJECTIVE: To develop and validate a simple, integer-based score to predict functional outcome in acute ischemic stroke (AIS) using variables readily available after emergency room admission. METHODS: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based point-scoring system for each covariate of the fitted multivariate model was generated by their β-coefficients; the overall score was calculated as the sum of the weighted scores. The model was validated internally using a 2-fold cross-validation technique and externally in 2 independent cohorts (Athens and Vienna Stroke Registries). RESULTS: Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) were identified as independent predictors of unfavorable outcome in 1,645 patients in ASTRAL. Their β-coefficients were multiplied by 4 and rounded to the closest integer to generate the score. The area under the receiver operating characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22 [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771 (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50% likelihood of unfavorable outcome. CONCLUSIONS: The ASTRAL score is a simple integer-based score to predict functional outcome using 6 readily available items at hospital admission. It performed well in double external validation and may be a useful tool for clinical practice and stroke research.

The temporoparietal fascia flap: a versatile tool in head and neck reconstruction.

PURPOSE OF REVIEW: The article reviews recent significant advances and current applications of the temporoparietal fascia flap (TPFF) in head and neck surgery. RECENT FINDINGS: The recent literature describes a wide span of new applications of the TPFF in many areas. Significant developments and refinements in the reconstruction of orbitomaxillary composite defects and orbital exenteration cavities are reported. The TPFF combined with alloplastic framework is gaining in importance in external ear reconstruction. Innovative prefabricated skin or soft-tissue grafts based on the TPFF are used to restore facial contour or in the reconstruction of complex facial defects. The free TPFF finds a role in laryngotracheal reconstruction as a vascular carrier to support cartilage grafts. SUMMARY: Owing to its reliability and unequalled structural properties, the TPFF still plays a central role in facial reconstruction. Future investigation will likely incorporate the free TPFF as a vascular carrier of bioengineered tissues, such as cartilage and mucosa, for various head and neck indications.

Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T lymphocytes using three-dimensional quantitative structure-activity relationships.

The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in immunology and in particular in peptide based immunotherapy. Here we develop three-dimensional (3D) quantitative structure-activity relationships (QSARs) to predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a previously developed ab initio structure prediction approach [Fagerberg et al., J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy calculations are performed on a 3D grid to produce similarity matrices which are combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59 (1997)] to generate 3D-QSAR models. The models are extensively validated using several different approaches. During the model generation, the leave-one-out cross-validated correlation coefficient (q (2)) is used as the fitness criterion and all obtained models are evaluated based on their q (2) values. Moreover, the best model obtained for a partitioned data set is evaluated by its correlation coefficient (r = 0.92 for the external test set). The physical relevance of all models is tested using a functional dependence analysis and the robustness of the models obtained for the entire data set is confirmed using y-randomization. Finally, the validated models are tested for their utility in the setting of rational peptide design: their ability to discriminate between peptides that only contain side chain substitutions in a single secondary anchor position is evaluated. In addition, the predicted cross-recognition of the mono-substituted peptides is confirmed experimentally in chromium-release assays. These results underline the utility of 3D-QSARs in peptide mimetic design and suggest that the properties of the unbound epitope are sufficient to capture most of the information to determine the cross-recognition.