Submitted by Rodolfo Santos Rossi null (rodolfosrossi@gmail.com) on 2017-06-20T19:44:52Z No. of bitstreams: 1 Rossi - Dissertação Repositório UNESP.pdf: 1649974 bytes, checksum: eab3c6db952f25d7d6aa51700765d11b (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-06-21T14:07:38Z (GMT) No. of bitstreams: 1 rossi_rs_me_bot.pdf: 1649974 bytes, checksum: eab3c6db952f25d7d6aa51700765d11b (MD5) / Made available in DSpace on 2017-06-21T14:07:38Z (GMT). No. of bitstreams: 1 rossi_rs_me_bot.pdf: 1649974 bytes, checksum: eab3c6db952f25d7d6aa51700765d11b (MD5) Previous issue date: 2017-04-27 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O objetivo deste estudo foi avaliar novas estratégias de identificação e tratamento de mastite subclínica causada por Streptococcus agalactiae. Dois estudos foram conduzidos para alcançar os objetivos propostos: 1) um ensaio clínico randomizado, para avaliar a eficácia do tratamento de S. agalactiae com cloxacilina intramamária (CLOXIMM), cefquinoma intramamária (CEFIMM) e cefquinoma intramuscular (CEFIM); e avaliar a não-inferioridade da CLOXIMM em relação a CEFIMM. E, 2) um estudo de acurácia diagnóstica, para estimar a acurácia do Somaticell, California Mastitis Test (CMT) e do exame microbiológico do leite composto (leite dos quatro quartos) na detecção de quartos e animais infectados com S. agalactiae. Os resultados indicaram que quartos tratados com CEFIM apresentaram menor taxa de cura bacteriológica (55%) do que aqueles tratados com CLOXIMM (86%) ou CEFIMM (98%). A diferença na proporção de cura bacteriológica entre CEFIMM e CLOXIMM foi de 0,121 (intervalo de confiança de 95%: 0,056 - 0,184). A CLOXIMM foi considerada não inferior a CEFIMM quando margens de não inferioridade de 0,20 e 0,25 foram utilizadas. Contudo, a determinação da não inferioridade foi inconclusiva para margens de 0,10 e 0,15. A cultura do leite composto apresentou acurácia diagnóstica satisfatória (95,7%) quando comparada a cultura individual por quarto. Para identificação dos quartos infectados com S. agalactiae, o ponto de corte considerado mais adequado foi de 205.000 células/mL para o teste Somaticell e escore 1 para o teste CMT. O teste Somaticell foi considerado mais acurado para uso em programas de erradicação, pois apresentou maior sensibilidade e menor proporção de resultados falso-negativos. Resultados deste estudo podem ser aplicados diretamente em nível de campo, para aumentar a eficiência de programas de erradicação de S. agalactiae. / The objective of the present study was to assess new strategies to identify and treat Streptococcus agalactiae subclinical mastitis. Two studies were conducted to achieve the proposed objectives: 1) a randomized clinical trial, to assess the efficacy of intramammary cloxacillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular cefquinome (CEFIM), to treat S. agalactiae intramammary infections (IMI); and assess whether CLOXIMM was non-inferior to CEFIMM to treat S. agalactiae IMI. And, 2) a diagnostic accuracy study, to estimate the accuracy of the Somaticell, California Mastitis Test (CMT), and the composite milk microbiological examination of milk to detect S. agalactiae IMI. Results indicated that the bacteriological cure rate was lower for quarters treated with CEFIM (55%), as compared with CLOXIMM (86%) or CEFIMM (98%). The bacteriological cure difference between CEFIMM and CLOXIMM was 0.121 (95% confidence interval: 0.056 - 0.184). The CLOXIMM was considered non-inferior to CEFIMM when the non-inferiority margins of 0.20 and 0.25 were considered. Nevertheless, determination of non-inferiority was inconclusive for margins of 0.10 and 0.15. Microbiological examination of composite milk was of high accuracy (95.7%), as compared with microbiological examination of quarter milk samples. The thresholds of 205,000 cells/mL for the Somaticell and of score 1 for the CMT can be considered the most appropriate for diagnosing S. agalactiae IMI. The higher sensitivity and lower proportion of false-negative results are characteristics that can justify the use of the Somaticell in S. agalactiae eradication programs, as an alternative to the CMT. Results of this study can be directly applied at the farm level, to improve the efficiency of S. agalactiae eradication programs. / CNPq: 132538-2015-6

In this work we want to examine selected models with nonlinear volatility and their properties. At the beginning we define models with non-constant variance, especially ARCH, GARCH and EGARCH models. Then we study the probability distributions that are mainly used in the EGARCH model. Then we focus on the EGARCH model, describe the conditions for stationarity and invertibility of the model, define diagnostic tests and QMLE estimates of parameters. In the last chapter we perform simulation studies of the selected models and their application to real data. 1

Syftet med den aktuella studien var att undersöka tillförlitligheten av apikal palpation och perkussion vid diagnostik av symtomatisk apikal parodontit och asymptomatisk apikal parodontit på icke rotfyllda tänder.Femton patienter undersöktes; åtta patienter med symtomatisk apikal parodontit och sju patienter med asymptomatisk apikal parodontit. Patienterna rekryterades från tre kliniker i södra Sverige. Först besvarade patienterna frågor om aktuellt läkemedelsintag och graderade sin smärta på en Visuell Analog Skala. Observatören utförde de två diagnostiska testerna på testtanden, kontrolltanden samt deras intilliggande tänder. Som referenstest kontrollerades pulpans tillstånd genom direkt inspektion vid kavumpreparation av testtanden. För apikal palpation, vid diagnostik av symtomatisk apikal parodontit/asymptomatisk apikal parodontit, var sensitiviteten 0,50/0,14, specificiteten 1/1, det positiva prediktiva värdet 1/1 samt det negativa prediktiva värdet 0,67/0,54. För perkussion, vid diagnostik av symtomatisk apikal parodontit/asymptomatisk apikal parodontit, var sensitiviteten 0,38/0,29, specificiteten 1/1, det positiva prediktiva värdet 1/1 samt det negativa prediktiva värdet 0,62/0,58. Inga generella slutsatser kan dras från studien på grund av den begränsade studiepopulationen. Resultatet indikerar dock att tillförlitligheten för apikal palpation och perkussion vid diagnostik av symtomatisk apikal parodontit och asymptomatisk apikal parodontit på icke-rotfyllda tänder är låg. Dessa två diagnostiska tester bör inte användas enskilt för att identifiera tänder med symtomatisk apikal parodontit och asymptomatisk apikal parodontit. / The aim of this study was to evaluate the accuracy of apical palpation and percussion when diagnosing symptomatic apical periodontitis and asymptomatic apical periodontitis in non-root filled teeth.Fifteen patients participated in the study; eight patients with symptomatic apical periodontitis and seven with asymptomatic apical periodontitis. The patients were recruited from three different clinics in the south of Sweden. Initially, the patients answered questions concerning recent intake of medication and graded their pain on a Visual Analogue Scale. The observer performed the two diagnostic tests on the test tooth, the control tooth and their adjacent teeth. As reference test, the pulp condition was examined by direct inspection at the access opening of the test tooth. For apical palpation, when diagnosing symptomatic apical periodontitis/asymptomatic apical periodontitis, the sensitivity was 0.50/0.14, the specificity was 1/1, the positive predictive value was 1/1 and the negative predictive value was 0.67/0.54. For percussion, when diagnosing symptomatic apical periodontitis /asymptomatic apical periodontitis, the sensitivity was 0.38/0.29, the specificity was 1/1, the positive predictive value was 1/1 and the negative predictive value was 0.62/0.58.No general conclusions can be made from this study due to the small population size. However, the results indicate that the accuracy of apical palpation and percussion when diagnosing symptomatic apical periodontitis and asymptomatic apical periodontitis in non-root filled teeth is low. The two diagnostic tests should not be used alone to identify teeth with symptomatic apical periodontitis and asymptomatic apical periodontitis.

Background: The standard of care for mediastinal staging during endobronchial ultrasound (EBUS) is Systematic Sampling (SS) where a minimum of 3 lymph node (LN) stations are biopsied, even if they appear normal on imaging. When LNs appear normal on PET and CT, the Canada Lymph Node Score can also identify if they appear normal on EBUS. For these Triple Normal LNs, the pretest probability of malignancy is < 6%, and routine biopsy may not be required. This preliminary study introduced Selective Targeted Sampling (STS), which omits biopsy of Triple Normal LNs and compared it firsthand to SS. Methods: A prospective, feasibility RCT was conducted to determine whether the progression of a definitive trial was warranted. Primary outcomes and their progression criterium were recruitment rate (70% acceptable minimum); procedure length (no overlap between sampling methods’ 95%CIs); and missed nodal metastasis (overlap between sampling methods’ diagnostic accuracy 95%CIs and crossing of the null for the percent difference in diagnosis). cN0-N1 NSCLC patients undergoing EBUS were randomized to the STS or SS arm. Patients in the STS arm were then crossed over to the SS arm to receive standard of care. Wilson’s CI method and McNemar’s test of paired proportions were used for statistical comparison. Surgical pathology was the reference standard. Results: Thirty-eight patients met the eligibility criteria, and all were recruited (100%; 95%CI: 90.82 to 100.00%). The median procedure lengths, in minutes, for STS and SS were 3.07 (95%CI: 2.33 to 5.52) and 19.07 (95%CI: 15.34 to 20.05) respectively. STS had a diagnostic accuracy of 100% (95%CI: 74.65% to 100.00%), whereas SS was 93.75% (95%CI: 67.71% to 99.67%) with the inclusion of inconclusive results. Percent difference in diagnosis between sampling method was 5.35% (95%CI: -0.54% to 11.25%). Conclusion: With the progression criteria successfully met, a subsequent multicentered, non-inferiority crossover trial comparing STS to SS is warranted. / Thesis / Master of Science (MSc) / Before deciding on treatment for patients with lung cancer, a critical step in the investigations is finding out whether the lymph nodes in the chest contain cancer. This is best done with a needle that biopsies those lymph nodes through the walls of the airway, known as endobronchial ultrasound transbronchial needle aspiration. Guidelines require that every lymph node in the chest be biopsied through a process called Systematic Sampling. However, new research has suggested that some lymph nodes may not need a biopsy. These lymph nodes are ones with a very low chance of cancer, based on their imaging tests. In this study, Selective Targeted Sampling was introduced whereby lymph nodes that appeared normal were not initially biopsied. The study followed a feasibility design, which proved sufficient patient interest, adequate safety and possible benefits in pursuing a larger trial comparing Selective Targeted Sampling to Systematic Sampling.

La majorité des personnes âgées atteintes de démence présente des symptômes comportementaux et psychologiques. Plusieurs instruments de mesure sont disponibles afin d’évaluer les troubles de comportement des personnes résidant en centre d’hébergement mais peu d’entre eux ont été traduits et validés en français. Ce mémoire a pour objectif principal de déterminer la structure factorielle de la version française du Nursing Home Behavior Problem Scale (NHBPS) auprès de personnes atteintes de démence et résidant en centre d’hébergement. Un objectif secondaire est de documenter les variables associées aux dimensions sous-jacentes de cet instrument. Les participants (N=155) ont un diagnostic de démence et sont usagers de trois centres d’hébergement et d’une unité de soins de longue durée d’un hôpital. Une infirmière a évalué les troubles du comportement des participants à l’aide du NHBPS ainsi que leurs caractéristiques personnelles. Une analyse factorielle confirmatoire montre un manque d’adéquation des données à deux solutions factorielles de la version anglaise du NHBPS. Une analyse en composantes principales révèle cinq dimensions expliquant 58 % de la variance. Plusieurs variables, notamment la consommation d’antipsychotiques, la présence d’un delirium, la douleur et la dépression, sont associées au score total du NHBPS et à ses différentes dimensions sous-jacentes. Bien que la solution factorielle de la version française du NHBPS soit similaire à celle de la version originale anglaise, nos résultats montrent également des différences qui peuvent dépendre de facteurs méthodologiques et culturels.

The diagnosis of Parkinson’s disease (PD) follows the UK Brain Bank Criteria, which demands bradykinesia and one additional symptom, i.e. rigidity, resting tremor or postural instability. The latter is not a useful sign for the early diagnosis of PD, because it does not appear before Hoehn and Yahr stage 3. Early symptoms of PD which precede the onset of motor symptoms are hyposmia, REM sleep behavioral disorder, constipation, and depression. In addition, an increasing number of patients whose PD is related to a genetic defect are being described. Thus, genetic testing may eventually develop into a tool to identify at-risk patients. The clinical diagnosis of PD can be supported by levodopa or apomorphine tests. Imaging studies such as cranial CT or MRI are helpful to distinguish idiopathic PD from atypical or secondary PD. SPECT and PET methods are valuable to distinguish PD tremor from essential tremor if this is clinically not possible. Using all of these methods, we may soon be able to make a premotor diagnosis of PD, which will raise the question whether early treatment is possible and ethically and clinically advisable. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Many continuous medical tests often rely on a threshold for diagnosis. There are two sequential testing strategies of interest: Believe the Positive (BP) and Believe the Negative (BN). BP classifies a patient positive if either the first test is greater than a threshold θ1 or negative on the first test and greater than θ2 on the second test. BN classifies a patient positive if the first test is greater than a threshold θ3 and greater than θ4 on the second test. Threshold pairs θ = (θ1, θ2) or (θ3, θ4), depending on strategy, are defined as optimal if they maximized GYI = Se + r(Sp – 1). Of interest is to determine if these optimal threshold, or optimal operating point (OOP), estimates are “good” when calculated from a sample. The methods proposed in this dissertation derive formulae to estimate θ assuming tests follow a binormal distribution, using the Newton-Raphson algorithm with ridging. A simulation study is performed assessing bias, root mean square error, percentage of over estimation of Se/Sp, and coverage of simultaneous confidence intervals and confidence regions for sets of population parameters and sample sizes. Additionally, OOPs are compared to the traditional empirical approach estimates. Bootstrapping is used to estimate the variance of each optimal threshold pair estimate. The study shows that parameters such as the area under the curve, ratio of standard deviations of disease classification groups within tests, correlation between tests within a disease classification, total sample size, and allocation of sample size to each disease classification group were all influential on OOP estimation. Additionally, the study shows that this method is an improvement over the empirical estimate. Equations for researchers to use in estimating total sample size and SCI width are also developed. Although the models did not produce high coefficients of determination, they are a good starting point for researchers when designing a study. A pancreatic cancer dataset is used to illustrate the OOP estimation methodology for sequential tests.

Pharmakodiagnostische Tests eröffnen die Möglichkeit, Krebstherapien individueller auf den Patienten zugeschnitten zu verschreiben. Die vorliegende Dissertation widmet sich deshalb der Frage, wie diese Gruppen in Deutschland sowie den USA in Bezug auf diese Tests Entscheidungen treffen. Alle im Rahmen dieser Arbeit durchgeführten Studien waren unterteilt in eine Vorstudie und eine Hauptsstudie. Die Ergebnisse der Vorstudie wurden im Rahmen der Hauptstudie zur Entwicklung eines Fall-Vignetten Fragebogens benutzt,um die Verwendung von kompensatorischen und nicht-kompensatorischen Entscheidungsstrategien zu untersuchen. Mit Studie I wurde gezeigt, dass sowohl deutsche als auch amerikanische Onkologen eine hohe Bereitschaft haben, solche Tests anzuwenden. Die entsprechenden Entscheidungen wurden am besten durch ein kompensatorisches Modell (Franklin’s Rule)vorhergesagt. Eine Leitlinien-Empfehlung führte nahezu immer zu einer Test-Entscheidung. Verschiedene Bedingungen machten eine Entscheidung für nicht-empfohlene Tests jedoch wahrscheinlicher. Studie II zeigte, dass Pathologen nur zu einem beschränkten Ausmaß bereit waren, von dem etablierten Test-Standard für neuartige Test-Prozeduren abzuweichen. Die Entscheidungsstrategie beider Gruppen wurde gleich gut durch die jeweiligen kompensatorischen Modelle (Franklin’s und Dawes’ Rule) sowie durch das nicht-kompensatorische Modell (Take The Best) vorhergesagt. Für die mit Studie III untersuchten Krebspatienten zeigte sich, dass ein nicht-kompensatorisches Modell (Matching Heuristic) die besten Entscheidungs-Vorhersagen machte.Während die Entscheidungen der US Patienten jedoch maßgeblich von einer Arzt-Empfehlung geleitet waren, fand sich dies nicht für die deutschen Patienten. Die sich aus den Befunden ergebenden Implikationen für die hier untersuchten Gruppen, für die mit der Leitlinien-Entwicklung beauftragten Autoritäten als auch für das Gesundheitssystem im Allgemeinen wurden abschließend diskutiert. / Upcoming pharmacodiagnostic tests offer the opportunity to better tailor cancer treatment decisions to individual patient needs. However, they put oncologists, pathologists, and cancer patients in the position of having to deal with a new technology, which often comes with its own specific risks. Little is known about how these different groups will handle this situation. This thesis is a first effort to examine, within Germany and the USA, how the respective groups would deal with a decision on applying such a test to a cancer treatment decision. All accomplished studies were divided into an explorative pilot study and a main study. Results of the pilot study were used for the main study to develop a case vignette questionnaire in order to investigate compensatory and noncompensatory decision-making strategies.In Study I, it was found that both, German and US oncologists’ decision-making policies were best described by a compensatory model (Franklin’s rule). A recommendation of a test by guidelines triggered nearly always a choice for having the test, although under different conditions also choices for nonrecommended tests were likely. Study II found that pathologists were, to a rather small extent, prepared to opt for more sophisticated test alternatives, compared to standard procedures. For both samples, decision making was equally well-predicted by two compensatory models (Franklin’s rule and Dawes’ rule), as it was by a noncompensatory model (Take The Best.Study III focused on cancer patients. The German as well as the US patients’ decisions were best predicted by a noncompensatory model (Matching Heuristic), while for the US patients, the most impacting cue was the recommendation by an oncologist, what could not be found for the German sample.Several implications of these findings for the respective groups, for authorities in charge of developing guidelines, as well as for the health systems in general, are discussed.

Made available in DSpace on 2016-04-27T16:58:31Z (GMT). No. of bitstreams: 1 Maria da Conceicao de Oliveira Malaspina.pdf: 2306045 bytes, checksum: 84a5df81fa1b298e1b3d2d212661d47e (MD5) Previous issue date: 2007-10-02 / Secretaria da Educação do Estado de São Paulo / The purpose of this dissertation was to do an interventionist study for the introduction of the fraction concept to 2nd graders. The study proposed to answer the following research question: What are the effects that each of the four meanings of the fraction (part-whole, quotient, multiplicative operator and measurement) bring to the initial learning of 2nd graders about this concept? For such, a study with 61 students was done, coming from two classes of a state public school of the Santo André zone, which composed two groups, one of the groups passed through a planned intervention of teaching about the fraction theme Experimental Group (GE) and the other group did not pass though any intervention about the theme, and because of that, it was called Control Group (GC). Both groups have never had contact, from the formal view of the school, with the fraction object. The theoretical foundation of the research counted with the Theory of Conceptual Fields proposed by Vergnaud (1988; 2001) and the theoretical ideas from Nunes et al. (2003) with relation to the different meanings of fractions. The methodology counted with a near-experimental study divided into two steps: the first one, denominated step &#56256;&#56388;, referred to the collective application of three diagnostic tests (pre, intermediate and pos test) for both students from GE and GC that answered individually. The second one, called step &#56256;&#56389;, turned itself to the intervention phase, moment in which the students from the GE and the GC were divided into 4 subgroups in which two meanings of fractions were taught. The data were analyzed inside these two moments, one turned to the quantitative analysis in which was tried to relate the percentage of right answers, with help from the SPSS (Statistical Package for Social Science) The second moment referred to the analysis of the data from a qualitative point of view, aiming at identifying kind of mistakes made by the students, as well as to analyze its strategies in the resolution. The results showed that each of the meanings had an important role in the learning of the fraction by the students and they all brought contributions to the beginning of the appropriation of this object. Thus, it was possible to find distinct effects in the initial learning of fraction, depending on the meaning that was used to introduce this concept / A presente dissertação teve por objetivo realizar um estudo intervencionista para introdução do conceito de fração com alunos da 2ª série do Ensino Fundamental. O estudo propôs-se a responder à seguinte questão de pesquisa: Quais os efeitos que cada um dos quatro significados para fração (parte-todo, quociente, operador multiplicativo e medida) traz para a aprendizagem inicial dos alunos do 1º ciclo (2ª série) do Ensino Fundamental sobre esse conceito? Para tanto, foi realizado um estudo com 61 alunos, advindos de duas turmas de uma escola pública estadual da região de Santo André, que compuseram dois grupos; um dos grupos passou por uma intervenção planejada de ensino sobre o tema fração Grupo Experimental (GE) e o outro grupo não passou por qualquer intervenção sobre o tema, e por isso, foi chamado de Grupo Controle (GC). Ambos os grupos, nunca tiveram contato, do ponto de vista formal da escola, com o objeto fração. A fundamentação teórica da pesquisa contou com a Teoria dos Campos Conceituais proposta por Vergnaud (1988; 2001) e as idéias teóricas de Nunes et al. (2003) com relação aos diferentes significados da fração. A metodologia constou de um estudo quase-experimental dividido em duas etapas: a primeira, denominada etapa &#56256;&#56388;, referiu-se a aplicação coletiva dos três testes-diagnóstico (pré, intermediário e pós-teste) tanto aos alunos do GE quanto GC que responderam individualmente. A segunda, chamada de etapa &#56256;&#56389;, voltou-se para fase de intervenção, momento em que dividimos aos alunos do GE em quatro subgrupos nos quais foram ensinados dois significados da fração.Os dados foram analisados dentro de dois momentos: um voltado à análise quantitativa em que se buscou relacionar os percentuais de acerto, com ajuda a do pacote estatístico SPSS (Statistical Package for Social Sciene). O segundo momento referiu-se a análise dos dados do ponto de vista qualitativo, visando identificar os tipos de erros cometidos pelos alunos, bem como analisar suas estratégias na resolução. Os resultados mostraram que cada um dos significados teve papel importante na aprendizagem da fração pelos alunos e todos trouxeram contribuições para o início da apropriação desse objeto. Dessa forma, foi possível encontrar efeitos distintos na aprendizagem inicial de fração, dependendo do significado que se utilizou para introduzir esse conceito

<p>This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.</p><p>GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.</p><p>In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.</p> / On the day of the public defence the status of the articles IV and V was: Accepted.