Mammography-based screening program: preliminary results from a first 2-year round in a Brazilian region using mobile and fixed units

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths among women worldwide. The use of mobile mammography units to offer screening to women living in remote areas is a rational strategy to increase the number of women examined. This study aimed to evaluate results from the first 2 years of a government-organized mammography screening program implemented with a mobile unit (MU) and a fixed unit (FU) in a rural county in Brazil. The program offered breast cancer screening to women living in Barretos and the surrounding area. Methods: Based on epidemiologic data, 54 238 women, aged 40 to 69 years, were eligible for breast cancer screening. The study included women examined from April 1, 2003 to March 31, 2005. The chi-square test and Bonferroni correction analyses were used to evaluate the frequencies of tumors and the importance of clinical parameters and tumor characteristics. Significance was set at p < 0.05. Results: Overall, 17 964 women underwent mammography. This represented 33.1% of eligible women in the area. A mean of 18.6 and 26.3 women per day were examined in the FU and MU, respectively. Seventy six patients were diagnosed with breast cancer (41 (54%) in the MU). This represented 4.2 cases of breast cancer per 1000 examinations. The number of cancers detected was significantly higher in women aged 60 to 69 years than in those aged 50 to 59 years (p < 0.001) or 40 to 49 years (p < 0.001). No difference was observed between women aged 40 to 49 years and those aged 50 to 59 years (p = 0.164). The proportion of tumors in the early (EC 0 and EC I) and advanced (CS III and CS IV) stages of development were 43.4% and 15.8%, respectively. Conclusions: Preliminary results indicate that this mammography screening program is feasible for implementation in a rural Brazilian territory and favor program continuation.

Haplotype frequencies based on eight polymorphic sites at the 3' untranslated region of the HLA-G gene in individuals from two different geographical regions of Brazil

The Brazilian population represents an admixture of native Amerindians, Portuguese settlers and Africans who were brought as slaves during the colonization period that began in the 16th century and was followed by waves of immigrations of Europeans and Asians in the 20th century. The contribution of these different ethnic groups to the constitution of Brazilian populations from different geographic regions is variable and, in addition to environmental factors, might act by determining different allele profiles among Brazilian populations from different regions. We studied polymorphic sites at the 3' untranslated region of the HLA-G gene in individuals from a Northeastern Brazilian region and compared them to our previously published data about a Southeastern Brazilian region, located at a distance of 2589 km. Our results showed that most polymorphic sites present a similar distribution in both populations, except for the lower frequency of the +3003C allele in the Northeastern population compared to the Southeastern population. Although differences in genotypic distribution were only significant for the +3003 locus (P = 0.0201), the diversity of haplotypes was distinct for each population. These results are important for casecontrol studies on the association of human leucocyte antigen-G polymorphism with disease and also in terms of the genetic structure of two distinct Brazilian populations.

Epidemiology of vampire bat-transmitted rabies virus in Goiás, central Brazil: re-evaluation based on G-L intergenic region

Abstract Background Vampire bat related rabies harms both livestock industry and public health sector in central Brazil. The geographical distributions of vampire bat-transmitted rabies virus variants are delimited by mountain chains. These findings were elucidated by analyzing a high conserved nucleoprotein gene. This study aims to elucidate the detailed epidemiological characters of vampire bat-transmitted rabies virus by phylogenetic methods based on 619-nt sequence including unconserved G-L intergenic region. Findings The vampire bat-transmitted rabies virus isolates divided into 8 phylogenetic lineages in the previous nucleoprotein gene analysis were divided into 10 phylogenetic lineages with significant bootstrap values. The distributions of most variants were reconfirmed to be delimited by mountain chains. Furthermore, variants in undulating areas have narrow distributions and are apparently separated by mountain ridges. Conclusions This study demonstrates that the 619-nt sequence including G-L intergenic region is more useful for a state-level phylogenetic analysis of rabies virus than the partial nucleoprotein gene, and simultaneously that the distribution of vampire bat-transmitted RABV variants tends to be separated not only by mountain chains but also by mountain ridges, thus suggesting that the diversity of vampire bat-transmitted RABV variants was delimited by geographical undulations.

Comparative performance evaluation of hepatitis C virus genotyping based on the 5' untranslated region versus partial sequencing of the NS5B region of brazilian patients with chronic hepatitis C

Background Genotyping of hepatitis C virus (HCV) has become an essential tool for prognosis and prediction of treatment duration. The aim of this study was to compare two HCV genotyping methods: reverse hybridization line probe assay (LiPA v.1) and partial sequencing of the NS5B region. Methods Plasma of 171 patients with chronic hepatitis C were screened using both a commercial method (LiPA HCV Versant, Siemens, Tarrytown, NY, USA) and different primers targeting the NS5B region for PCR amplification and sequencing analysis. Results Comparison of the HCV genotyping methods showed no difference in the classification at the genotype level. However, a total of 82/171 samples (47.9%) including misclassification, non-subtypable, discrepant and inconclusive results were not classified by LiPA at the subtype level but could be discriminated by NS5B sequencing. Of these samples, 34 samples of genotype 1a and 6 samples of genotype 1b were classified at the subtype level using sequencing of NS5B. Conclusions Sequence analysis of NS5B for genotyping HCV provides precise genotype and subtype identification and an accurate epidemiological representation of circulating viral strains.

Determinants of cesarean delivery, a population-based study in the Emilia Romagna Region

Cesarean Delivery (CD) rates are rising in many parts of the world. In order to define strategies to reduce them, it is important to explore the role of clinical and organizational factors. This thesis has the objective to describe the contemporary CD practice and study clinical and organizational variables as determinants of CD in all women who gave birth between 2005 and June 2010 in the Emilia Romagna region (Italy). All hospital discharge abstracts of women who delivered between 2005 and mid 2010 in the region were selected and linked with birth certificates. In addition to descriptive statistics, in order to study the role of clinical and organizational variables (teaching or non-teaching hospital, birth volumes, time and day of delivery) multilevel Poisson regression models and a classification tree were used. A substantial inter-hospital variability in CD rate was found, and this was only partially explained by the considered variables. The most important risk factors of CD were: previous CD (RR 4,95; 95%CI: 4,85-5,05), cord prolapse (RR 3,51; 95% CI:2,96-4,16), and malposition/malpresentation (RR 2,72; 95%CI: 2,66-2,77). Delivery between 7 pm and 7 am and during non working days protect against CD in all subgroups including those with a small number of elective CDs while delivery at a teaching hospital and birth volumes were not statistically significant risk factors. The classification tree shows that previous CD and malposition/malpresentation are the most important variables discriminating between high and low risk of CD. These results indicate that other not considered factors might explain CD variability and do not provide clear evidence that small hospitals have a poor performance in terms of CD rate. Some strategies to reduce CD could be found by focusing on the differences in delivery practice between day and night and between working and no-working day deliveries.

Maternal Smoking Impact on the Delivery Cost: a population-based study in the Emilia-Romagna region

This doctoral thesis is devoted to the study of the causal effects of the maternal smoking on the delivery cost. The interest of economic consequences of smoking in pregnancy have been studied fairly extensively in the USA, and very little is known in European context. To identify the causal relation between different maternal smoking status and the delivery cost in the Emilia-Romagna region two distinct methods were used. The first - geometric multidimensional - is mainly based on the multivariate approach and involves computing and testing the global imbalance, classifying cases in order to generate well-matched comparison groups, and then computing treatment effects. The second - structural modelling - refers to a general methodological account of model-building and model-testing. The main idea of this approach is to decompose the global mechanism into sub-mechanisms though a recursive decomposition of a multivariate distribution.

Novel algorithms for electronic structure based molecular dynamics with linear system-size scaling

Die vorliegende Arbeit behandelt die Entwicklung und Verbesserung von linear skalierenden Algorithmen für Elektronenstruktur basierte Molekulardynamik. Molekulardynamik ist eine Methode zur Computersimulation des komplexen Zusammenspiels zwischen Atomen und Molekülen bei endlicher Temperatur. Ein entscheidender Vorteil dieser Methode ist ihre hohe Genauigkeit und Vorhersagekraft. Allerdings verhindert der Rechenaufwand, welcher grundsätzlich kubisch mit der Anzahl der Atome skaliert, die Anwendung auf große Systeme und lange Zeitskalen. Ausgehend von einem neuen Formalismus, basierend auf dem großkanonischen Potential und einer Faktorisierung der Dichtematrix, wird die Diagonalisierung der entsprechenden Hamiltonmatrix vermieden. Dieser nutzt aus, dass die Hamilton- und die Dichtematrix aufgrund von Lokalisierung dünn besetzt sind. Das reduziert den Rechenaufwand so, dass er linear mit der Systemgröße skaliert. Um seine Effizienz zu demonstrieren, wird der daraus entstehende Algorithmus auf ein System mit flüssigem Methan angewandt, das extremem Druck (etwa 100 GPa) und extremer Temperatur (2000 - 8000 K) ausgesetzt ist. In der Simulation dissoziiert Methan bei Temperaturen oberhalb von 4000 K. Die Bildung von sp²-gebundenem polymerischen Kohlenstoff wird beobachtet. Die Simulationen liefern keinen Hinweis auf die Entstehung von Diamant und wirken sich daher auf die bisherigen Planetenmodelle von Neptun und Uranus aus. Da das Umgehen der Diagonalisierung der Hamiltonmatrix die Inversion von Matrizen mit sich bringt, wird zusätzlich das Problem behandelt, eine (inverse) p-te Wurzel einer gegebenen Matrix zu berechnen. Dies resultiert in einer neuen Formel für symmetrisch positiv definite Matrizen. Sie verallgemeinert die Newton-Schulz Iteration, Altmans Formel für beschränkte und nicht singuläre Operatoren und Newtons Methode zur Berechnung von Nullstellen von Funktionen. Der Nachweis wird erbracht, dass die Konvergenzordnung immer mindestens quadratisch ist und adaptives Anpassen eines Parameters q in allen Fällen zu besseren Ergebnissen führt.

Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy

BACKGROUND: The activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme of pyrimidine catabolism, is thought to be an important determinant for the occurrence of severe toxic reactions to 5-fluorouracil (5-FU), which is one of the most commonly prescribed chemotherapeutic agents for the treatment of solid cancers. Genetic variation in the DPD gene (DPYD) has been proposed as a main factor for variation in DPD activity in the population. However, only a small proportion of severe toxicities in 5-FU based chemotherapy can be explained with such rare deleterious DPYD mutations resulting in severe enzyme deficiencies. Recently, hypermethylation of the DPYD promoter region has been proposed as an alternative mechanism for DPD deficiency and thus as a major cause of severe 5-FU toxicity. METHODS: Here, the prognostic significance of this epigenetic marker with respect to severe 5-FU toxicity was assessed in 27 cancer patients receiving 5-FU based chemotherapy, including 17 patients experiencing severe toxic side effects following drug administration, none of which were carriers of a known deleterious DPYD mutation, and ten control patients. The methylation status of the DPYD promoter region in peripheral blood mononuclear cells was evaluated by analysing for each patient between 19 and 30 different clones of a PCR-amplified 209 base pair fragment of the bisulfite-modified DPYD promoter region. The fragments were sequenced to detect bisulfite-induced, methylation-dependent sequence differences. RESULTS: No evidence of DPYD promoter methylation was observed in any of the investigated patient samples, whereas in a control experiment, as little as 10% methylated genomic DNA could be detected. CONCLUSION: Our results indicate that DYPD promoter hypermethylation is not of major importance as a prognostic factor for severe toxicity in 5-FU based chemotherapy.

Algorithms for spacecraft formation flying navigation based on wireless positioning system measurements

Spacecraft formation flying navigation continues to receive a great deal of interest. The research presented in this dissertation focuses on developing methods for estimating spacecraft absolute and relative positions, assuming measurements of only relative positions using wireless sensors. The implementation of the extended Kalman filter to the spacecraft formation navigation problem results in high estimation errors and instabilities in state estimation at times. This is due tp the high nonlinearities in the system dynamic model. Several approaches are attempted in this dissertation aiming at increasing the estimation stability and improving the estimation accuracy. A differential geometric filter is implemented for spacecraft positions estimation. The differential geometric filter avoids the linearization step (which is always carried out in the extended Kalman filter) through a mathematical transformation that converts the nonlinear system into a linear system. A linear estimator is designed in the linear domain, and then transformed back to the physical domain. This approach demonstrated better estimation stability for spacecraft formation positions estimation, as detailed in this dissertation. The constrained Kalman filter is also implemented for spacecraft formation flying absolute positions estimation. The orbital motion of a spacecraft is characterized by two range extrema (perigee and apogee). At the extremum, the rate of change of a spacecraft’s range vanishes. This motion constraint can be used to improve the position estimation accuracy. The application of the constrained Kalman filter at only two points in the orbit causes filter instability. Two variables are introduced into the constrained Kalman filter to maintain the stability and improve the estimation accuracy. An extended Kalman filter is implemented as a benchmark for comparison with the constrained Kalman filter. Simulation results show that the constrained Kalman filter provides better estimation accuracy as compared with the extended Kalman filter. A Weighted Measurement Fusion Kalman Filter (WMFKF) is proposed in this dissertation. In wireless localizing sensors, a measurement error is proportional to the distance of the signal travels and sensor noise. In this proposed Weighted Measurement Fusion Kalman Filter, the signal traveling time delay is not modeled; however, each measurement is weighted based on the measured signal travel distance. The obtained estimation performance is compared to the standard Kalman filter in two scenarios. The first scenario assumes using a wireless local positioning system in a GPS denied environment. The second scenario assumes the availability of both the wireless local positioning system and GPS measurements. The simulation results show that the WMFKF has similar accuracy performance as the standard Kalman Filter (KF) in the GPS denied environment. However, the WMFKF maintains the position estimation error within its expected error boundary when the WLPS detection range limit is above 30km. In addition, the WMFKF has a better accuracy and stability performance when GPS is available. Also, the computational cost analysis shows that the WMFKF has less computational cost than the standard KF, and the WMFKF has higher ellipsoid error probable percentage than the standard Measurement Fusion method. A method to determine the relative attitudes between three spacecraft is developed. The method requires four direction measurements between the three spacecraft. The simulation results and covariance analysis show that the method’s error falls within a three sigma boundary without exhibiting any singularity issues. A study of the accuracy of the proposed method with respect to the shape of the spacecraft formation is also presented.

A comparison of pixel and object-based land cover classification. A case study of the Asmara region, Eritrea

In this paper we compare the performance of two image classification paradigms (object- and pixel-based) for creating a land cover map of Asmara, the capital of Eritrea and its surrounding areas using a Landsat ETM+ imagery acquired in January 2000. The image classification methods used were maximum likelihood for the pixel-based approach and Bhattacharyya distance for the object-oriented approach available in, respectively, ArcGIS and SPRING software packages. Advantages and limitations of both approaches are presented and discussed. Classifications outputs were assessed using overall accuracy and Kappa indices. Pixel- and object-based classification methods result in an overall accuracy of 78% and 85%, respectively. The Kappa coefficient for pixel- and object-based approaches was 0.74 and 0.82, respectively. Although pixel-based approach is the most commonly used method, assessment and visual interpretation of the results clearly reveal that the object-oriented approach has advantages for this specific case-study.