Thesis advisor: Gregory R. Chiklis / Thesis advisor: Kathleen Dunn / In molecular diagnostics, the polymerase chain reaction (PCR) is used to amplify small amounts of nucleic acids found in patient samples, allowing for detection of diseases within hours of infection. This early detection allows medical professionals to diagnose and treat patients with greater success. It is crucial that internal controls, such as NATtrol™-treated microorganisms, are used in these PCR assays to avoid false-negative results and ensure accurate diagnosis of patients. NATtrol™ treatment renders microorganisms non-infectious while leaving them fully intact with their complete RNA or DNA genomes. Therefore, NATtrol™-treated microorganisms can be used in PCR as full-process internal controls that are spiked into patient samples and co-extracted and co-amplified within the sample. If the spiked NATtrol™ control returns expected results on the test, then the patient sample result can also be trusted. Here, we performed studies to validate the use of NATtrol™-treated MS2 virus as a universal full-process internal molecular control. In these studies, a quantitative, real-time, reverse-transcription PCR (qRT-PCR) assay was performed on the Roche LightCycler 480 instrument. Studies included working range validation, limit of detection, within-run precision, between-run precision, real-time stability, freeze-thaw (transport) stability, and open-vial (use-life) stability. All studies demonstrated the precision and stability of the MS2 NATtrol™ molecular control. / Thesis (BS) — Boston College, 2014. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Biology Honors Program. / Discipline: Biology.

Over 80% of colorectal cancers (CRCs) are sporadic/randomly arising tumors. Interval CRCs represent a subset of sporadic tumors that develop within 6-36 months after a negative colonoscopy. Interval CRCs are suggested to exhibit altered biological properties that contribute to rapid growth and proliferation. We hypothesize that chromosomal instability (CIN), or aberrant chromosome numbers, contributes to the etiology of Interval CRCs. We have assembled a Manitoban cohort of Interval and sporadic (control) CRC tumor samples, and established a fluorescence in situ hybridization approach to characterize CIN by enumerating specific chromosomes. The results of this study indicate that 75% of Interval CRCs exhibit a CIN phenotype, making CIN the most prevalent contributor to genomic instability in Interval CRCs. Only once we grasp a better understanding of the tumorigenic pathways through which Interval CRCs develop, can we tailor screening strategies and treatment options to specifically identify and combat this subset of sporadic CRC.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 3 uppsatser.

Forensic biology encompasses the examination of evidentiary items from crime scenes for biological fluids, often identifying the specific biological fluid present and developing a DNA profile that can be used to link a suspect to a crime. Blood identification consists of visual examination, presumptive tests based on the catalytic activity of hemoglobin, and confirmatory tests based on antigen-antibody interactions. Issues encountered in blood identification include the occurrence of false positive and false negative results. Many causes of these results are well-known but more recently three substances resulting in false negatives with catalytic color tests, chemiluminescent reagents, and immunoassays have been explored. Quebracho extract (a common leather tannin), sodium percarbonate (the main component of detergents containing active oxygen) and vitamin C-containing beverages were all found to produce false negative results at varying degrees with each of the tests mentioned. Increased knowledge of potential negative interfering agents by forensic investigators can help ensure that probative evidence is properly collected and thoroughly analyzed from a crime scene.

Made available in DSpace on 2014-07-29T15:29:21Z (GMT). No. of bitstreams: 1 dissertacao cinara.pdf: 960645 bytes, checksum: 9e3f7530f507e4177c883e16350478e2 (MD5) Previous issue date: 2010-03-03 / Introduction: The External Quality Monitoring (MEQ) was developed from recommendations of the National Cancer Institute, in order to evaluate the performance of cytopathology diagnostic of the cervix and provide subsidies for continuing education to professionals in laboratories that provide services to public health. Objectives: To evaluate the results of Pap cervical smear between the laboratories accredited by the Single Health System (SUS) according to the diagnostic of the Unit of External Quality Monitoring (UMEQ), checking the frequency of the results of Pap cervical smear, the discordant cases, false positives (FP), false negative (FN) and diagnostic agreement. Methods: A total of 14 laboratories accredited by the SUS indicated by the Municipal Secretary of Health in Goiânia-GO participated in this study. It was reviewed the period from January 2007 to December 2008, Pap cervical smear tests selected by the Information System of Cancer of the cervix including all positive cases, all unsatisfactory ones and at least 5% of negative test results which should achieve at least 10% of the monthly routine of each laboratory, totaling 10,053 tests. These were reviewed by professionals from UMEQ / Faculty of Pharmacy from Federal University of Goiás. It was considered discordant cases in which there was a change in clinical management in accordance with the criteria established by the Ministry of Health. To place the cytological cervical results the Bethesda System was used. The magnitude of agreement was evaluated between the diagnoses using the kappa coefficient. The level of agreement considering its respective confidence intervals of 95% depending on the need to assign different weights to the disagreements were classified as follows: less than 0 - very bad agreement, 0 to 0.2, bad agreement; from 0.2 to 0.4 - reasonable agreement, from 0.4 to 0.6 - good agreement, from 0.6 to 0.8 - very good agreement and from 0.8 to 1.0 excellent. Results: There was disagreement between the UMEQ and laboratories of origin in 763 (7,59%) cases, of these 110 (1,1%) were FN distributed in: 37 (0,37%) atypical squamous cells of undetermined significance (ASC-US), 22 (0,22%) intraepithelial low-grade squamous lesions (LSIL), 30 (0,30%) atypical squamous cells cannot exclude a high-grade lesion (ASC-H), 12 (0,13%) squamous intraepithelial lesions of high grade (HSIL), an (0,01%) intraepithelial lesion of high-grade with suspicious features for invasion, six (0,07%) atypical glandular cells and two (0,02%) adenocarcinomas in situ. There was a delay in clinical management in 245 (2,44%) cases, of these 85 (0,84%) were initially classified as ASC-US and 160 (1,50%) as LSIL.The cases of ASC-US were distributed in: 53 (0,53%) ASC-H, 31 (0,31%) HSIL and an (0,01%) atypical glandular. The cases of LSIL were distributed in: 19 (0,19%) ASC-H, 139 (1,38%) HSIL and two (0,02%) atypical glandular cells. It was considered 283 (2,82%) FP cases and 125 (1,24%) initially negative cases that were reclassified as unsatisfactory. The agreement between the laboratories of origin and the UMEQ was excellent (Kappa = 0.81). It was found that for the evaluation of agreement of each laboratory, the majority showed very good agreement. The agreement of the sample adequacy was considered reasonable (Kappa = 0.30). Conclusion: Most laboratories showed very good agreement, however, it is worth mentioning that MEQ is an exercise of improvement needed to establish the standardization of diagnostic criteria and improve the accuracy of cervical smear. / O Monitoramento Externo da Qualidade (MEQ) foi elaborado a partir de recomendações do Instituto Nacional do Câncer, com o intuito de avaliar o desempenho dos diagnósticos citopatológicos do colo do útero e fornecer subsídios para educação continuada aos profissionais dos laboratórios que prestam serviços à rede pública de saúde. Objetivos: Avaliar os resultados dos exames citopatológicos do colo do útero dos laboratórios credenciados pelo Sistema Único de Saúde (SUS) de acordo com o diagnóstico da Unidade de Monitoramento Externo da Qualidade (UMEQ), verificando a frequência dos resultados dos exames citopatológicos do colo do útero, dos casos discordantes, falsopositivos (FP), falso-negativos (FN) e a concordância diagnóstica. Métodos: Participaram deste estudo 14 laboratórios credenciados pelo SUS indicados pela Secretária Municipal de Saúde de Goiânia-GO. Foram revisados, no período de janeiro de 2007 a dezembro de 2008, exames citopatológicos do colo do útero selecionados pelo Sistema de Informações do Câncer do Colo do Útero incluindo todos os casos positivos, todos os insatisfatórios e no mínimo 5% dos exames negativos devendo atingir no mínimo 10% da rotina mensal de cada laboratório, totalizando 10.053 exames. Estes foram revisados por profissionais da UMEQ/ Faculdade de Farmácia da Universidade Federal de Goiás. Foram considerados discordantes os casos em que houve mudança de conduta clínica de acordo com os critérios estabelecidos pelo Ministério da Saúde. Para a classificação dos resultados citopatológicos do colo do útero utilizou-se o Sistema de Bethesda. Avaliou-se a magnitude da concordância entre os diagnósticos utilizando o coeficiente Kappa. O nível de concordância ponderado com seus respectivos intervalos de confiança de 95% em função da necessidade de se atribuir diferentes pesos para as discordâncias foi classificado da seguinte forma: menor que 0 - concordância péssima; de 0 a 0,2-concordância ruim; de 0,2 a 0,4- concordância razoável; de 0,4 a 0,6- concordância boa; de 0,6 a 0,8- concordância muito boa e de 0,8 a 1,0- excelente. Resultados: Houve discordância entre a UMEQ e os laboratórios de origem em 763 (7,59%) casos, destes, 110 (1,1%) foram FN distribuídos em: 37 (0,37%) células escamosas atípicas de significado indeterminado (ASC-US), 22 (0,22%) lesões intra-epiteliais escamosas de baixo grau (LSIL), 30 (0,30%) células escamosas atípicas não é possível excluir uma lesão de alto grau (ASC-H), 12 (0,13%) lesões intraepiteliais escamosas de alto grau (HSIL), uma (0,01%) lesão intra-epitelial de alto grau com características suspeitas de invasão, seis (0,07%) atipias glandulares e dois (0,02%) adenocarcinomas in situ. Houve retardo na conduta clínica em 245 (2,44%) casos, destes, 85 (0,84%) foram inicialmente classificados como ASC-US e 160 (1,50%) como LSIL. Os casos de ASC-US distribuíram-se em: 53 (0,53%) ASC-H, 31 (0,31%) HSIL e uma (0,01%) atipia glandular. Os casos de LSIL distribuíram-se em: 19 (0,19%) ASC-H, 139 (1,38%) HSIL e duas (0,02%) atipias glandulares. Foram considerados 283 (2,82%) casos FP e 125 (1,24%) casos inicialmente negativos foram reclassificados como insatisfatórios. A concordância entre os laboratórios de origem e a UMEQ foi excelente (Kappa=0,81). Verificou-se que para a avaliação da concordância de cada laboratório, a maioria apresentou concordância muito boa. A concordância da adequabilidade da amostra foi considerada razoável (Kappa=0,30). Conclusão: A maioria dos laboratórios apresentou concordância muito boa, no entanto, vale ressaltar que o MEQ é um exercício de aprimoramento necessário para se estabelecer a padronização dos critérios diagnósticos e melhoria da acurácia dos exames citopatológicos.

Made available in DSpace on 2014-07-29T15:25:24Z (GMT). No. of bitstreams: 1 Tese-Edna Manrique.pdf: 787735 bytes, checksum: c22ee105b30898fd35080c35bcd1fc80 (MD5) Previous issue date: 2009-06-30 / Objectives: analyze the performance of the 100% rapid re-screening in detecting falsenegative results of cervical screening cervical, in quality control, after routine screening, using the average time of one and two minutes, according to final diagnosis. Methodology: a total 5,235 smears, classified as negative and unsatisfactory by routine screening, were submitted to 100% rapid re-screening method, using the time average of one and two minutes. In these reviews, the smears classified as unsatisfactory or suspects were subjected to detailed review. The concordant results were considered final diagnosis; the differences were meeting for a consensus that defined the final diagnosis. Results: of 5,235 smears submitted rapid re-screening method, of using the time of one minute and two minutes there was sensitivity and specificity of the final method of 64.3% and 99.2% for the time of one minute and two minutes was 63.8% and 99.5%. In smears, with satisfy adequacy for analysis, the sensitivity and specificity of this method, using the time of one and two minutes, were 64.2%, 98.9%, 61.5% and 99.4% respectively. The smears, with the adequacy of the smears presented for analysis limits, the sensitivity and specificity, using the time of one minute, was 64.7%, 99.9% and for two minutes were 70.6% and 99.8%. Of the total of 5,121 cervical smears, had 958 (18.7%) clinical information, after being submitted to rapid rescreening, using the time of one minute, 18 of those were suspects, of which ten were confirmed by final diagnosis as abnormal. When submitted to rapid re-screening using the time of two minutes, 13 were suspects, nine of these were confirmed by final diagnosis as abnormal. A total 4,163 (81.3%) smears had no clinical information, after being submitted to rapid re-screening, using the time of one minute were 70 suspects, of which 35 were classified as abnormal. When submitted to rapid re-screening using the time of two minutes were 54 suspects, of which 35 were confirmed by final diagnosis as abnormal. A rapid re-screening showed a sensitivity to smear with clinical information, using the time of one minute of 83.3% and for two minutes of 75%. Conclusions: the rapid re-screening method of 100% showed no difference in the detection of falsenegative results using the time of a minute or two. The adequacy of the sample does not influence the detection of false-negative results, using both a time as two minutes, and there was no difference in the detection of false-negative smears with and without clinical information using a time-two minutes and finally, in smears with clinical information / Objetivos: analisar o desempenho da revisão rápida de 100% na detecção de resultados falso-negativos dos exames citopatológicos cervicais, no controle da qualidade, após o escrutínio de rotina, utilizando o tempo médio de um e dois minutos, de acordo com o diagnóstico final. Metodologia: um total 5.235 esfregaços, classificados como negativos e insatisfatórios pelo escrutínio de rotina, foram submetidos à revisão rápida, utilizando os tempos médios de um e dois minutos. Nessas revisões, os esfregaços classificados como insatisfatórios ou suspeitos foram submetidos à revisão detalhada. Os resultados concordantes foram considerados como diagnóstico final, os divergentes foram para reunião de consenso que definiu o diagnóstico final. Resultados: dos 5.235 esfregaços submetidos ao método de revisão rápida utilizando o tempo de um e dois minutos, verificou-se uma sensibilidade e especificidade final desse método de 64,3% e 99,2% para o tempo de um minuto e para dois minutos foi 63,8% e 99,5%. Em esfregaços, com a adequabilidade da amostra satisfatória para análise, a sensibilidade e especificidade desse método, utilizando os tempos de um e dois minutos, foram de 64,2%, 98,9%, 61,5% e 99,4%, respectivamente. Em esfregaços, com a adequabilidade da amostra apresentando limitação para análise, a sensibilidade e especificidade, utilizando o tempo de um minuto, foi de 64,7% e 99,9%, para dois minutos foram de 70,6% e 99,8%. Do total de 5.121 esfregaços citopatológicos, 958 (18,7%) tinham informações clínicas, após serem submetidos à revisão rápida, utilizando o tempo de um minuto, 18 desses foram suspeitos, dos quais 10 foram confirmados pelo diagnóstico final como alterados. Quando submetidos à revisão rápida, utilizando o tempo de dois minutos, 13 foram suspeitos, entre eles, nove foram confirmados pelo diagnóstico final como alterados. Um total de 4.163 (81,3%) esfregaços não tinha informações clínicas, após serem submetidos à revisão rápida, utilizando o tempo de um minuto, 70 foram suspeitos, dos quais 35 foram classificados como alterados. Quando submetidos à revisão rápida, utilizando o tempo de dois minutos, 54 foram suspeitos, dos quais 35 foram confirmados pelo diagnóstico final como alterados. A revisão rápida apresentou uma sensibilidade, para esfregaços com informações clínicas, utilizando o tempo de um minuto de 83,3% e para dois minutos de 75%. Conclusões: o método de revisão rápida de 100% não apresentou diferença na detecção de resultados falso-negativos utilizando o tempo de um ou dois minutos. A adequabilidade da amostra não influencia na detecção de resultados falso-negativos, utilizando tanto o tempo de um como dois minutos, bem como não houve diferença na detecção de resultados falso-negativos em esfregaços com e sem informações clínicas através do método de revisão rápida, utilizando o tempo de um e dois minutos.

Bakgrund I dagens programvara finns det problem som försämrar kvaliteten hos system och ökar kostnaderna. Det är viktigt att tänka på säkerheten redan under programmeringsfasen för att underlätta underhåll. The Open Web Application Security Project (OWASP) erbjuder dokument, verktyg och projekt för att skapa och underhålla produkter på ett säkrare sätt. För att upptäcka säkerhetsproblem i koden kan verktyg för Static Application Security Testing (SAST) användas. SAST-verktyg kan rapportera både false negatives och false positives, därför är det viktigt att undersöka hur precisa verktygen är i sin rapportering. Syfte Studien ämnar kartlägga vilka SAST-verktyg utvecklare kan ta hjälp av för att skriva säkrare kod. Undersökningen skall även jämföra hur bra de är på att hitta sårbarheter i kod och hur stort antal false positives de rapporterar. Metod En sökning gjordes för att samla information om vilka SAST-verktyg som finns tillgängliga och en lista sammanställdes med krav för att kunna genomföra likvärdiga tester. För att utföra testerna användes kod med planterade sårbarheter och resultaten från testerna genererade kvantitativa data som fördes in i en tabell. Resultat I studiens resultat kartlades tolv SAST-verktyg. Från dessa valdes HCL AppScan CodeSweep, Snyk och SonarLint ut för vidare testning. Därefter beräknades recall, precision och false positives för verktygen. Snyk hade 71,43% på både recall och precision och 33,33% false positives. HCL AppScan CodeSweep hade 28,57% på recall, 57,14% på precision och 25% på false positives. SonarLint hittade inga sårbarheter och blev därav inte analyserat. Slutsatser Studien kartlade tolv olika SAST-verktyg och valde tre för likvärdiga tester av JavaScript i Visual Studio Code. Resultaten visade att Snyk presterade bäst gällande rapportering av sårbarheter och hade högre resultat gällande precision, medan HCL AppScan CodeSweep presterade bäst på att undvika false positives. Överlag anses Snyk vara studiens bästa SAST-verktyg då det hade högst resultat på både recall och precision. / Background In today's software, there are issues that degrade system quality and increase costs. It is important to consider security during the programming phase to facilitate maintenance. The Open Web Application Security Project (OWASP) provides documentation, tools, and projects to create and maintain products in a more secure manner. To detect security issues in the code, tools for Static Application Security Testing (SAST) can be used. SAST-tools can report both false negatives and false positives, so it is important to investigate the accuracy of the tools in their reporting. Aim The study aims to map which SAST-tools developers can utilize to write more secure code. The investigation will also compare their effectiveness inidentifying vulnerabilities in code and the numberof false positives they report. Method A search was conducted to gather information on available SAST-tools, and a list was compiled with requirements to perform equivalent tests. To carry out the tests, code with planted vulnerabilities was used, and the test results generated quantitative data that were entered into a table. Results The study's results mapped twelve SAST-tools. From these, HCL AppScan CodeSweep, Snyk, and SonarLint were selected for further testing. Then, the recall, precision, and false positives were calculated for the tools. Snyk achieved 71.43% for both recall and precision and had 33.33% false positives. HCL AppScan CodeSweep achieved 28.57% recall, 57.14% precision, and 25% false positives. SonarLint did not find any vulnerabilities and was therefore not analyzed. Conclusions The study surveyed twelve different SAST-tools and selected three for tests on JavaScript in Visual Studio Code. The results showed that Snyk performed the best in terms of vulnerability reporting and achieved higher precision results, while HCL AppScan CodeSweep excelled in avoiding false positives. Overall, Snyk is considered the best SAST-tool in the study as it had the highest results in both recall and precision.

No description available.

Made available in DSpace on 2014-07-29T15:29:13Z (GMT). No. of bitstreams: 1 Dissertacao Suelene Brito do Nascimento Tavares.pdf: 1452329 bytes, checksum: 6d86236e3c08daf9227c6b9f207128b7 (MD5) Previous issue date: 2007-09-06 / Cytopathology is an effective method of screening for cervical cancer; however, this method has high rates of false-negative results (FNR). To reduce FNR, routine measures of internal and external quality control are required in laboratories. The 10% random review of negative smears (R-10%) is the most commonly used method; however, it is not effective in reducing FNR. Nevertheless, there is evidence that the review of smears selected according to clinical risk factors (RCRF) and rapid prescreening (RPS) of all smears present good results. This study evaluated the performance of RPS, R-10% and RCRF as methods of internal quality control of cervical smear testing. The sample was composed of a total of 6,135 cervical smears from women who had attended Basic Health Clinics in Goiânia Goiás between March 2006 and March 2007. The cytopathological results were classified according to the 2001 Bethesda System. Initially, 6,135 smears were submitted to RPS followed by routine scrutiny (RS). Following RS, smears classified as negative were selected on the basis of clinical risk criteria, while 10% of all the smears were selected randomly, both sets then being submitted to the respective reviews. Four cytologists were responsible for RPS, RS, R-10% and RCRF, and three for reviewing the abnormal and discordant smears from any of the reviews. The smears classified as negative in RPS, RS, R-10% and RCRF were considered to have a final diagnosis (FD) of negative. Smears considered suspect or unsatisfactory at RPS were analyzed separately by two other cytologists. Smears considered abnormal or unsatisfactory at RS, R-10% and/or RCRF were likewise reviewed. When the two reviewing cytologists reached concordant diagnoses, these were considered the FD. Discordant results were analyzed by a third cytologist and a consensus meeting was held to define the FD. All stages of the study were performed blinded except for the consensus meeting. Smears classified as negative at RS, which were suspect at RPS and/or considered abnormal at R-10% and RCRF and confirmed abnormal in the FD, were considered FN results. Of the 6,135 smears, 5,522 were classified as negative, 84 as unsatisfactory and 529 as abnormal in the FD. Sensitivity of RPS was 63.0% for all abnormalities and 96.7% for high-grade squamous intraepithelial lesion (HSIL) compared to RS. The sensitivity of RPS was 74.9% for all abnormalities and 95.0% for HSIL compared to FD. The sensitivity of R-10% was 53.8% for all abnormalities when compared to FD. R-10% failed to detect any cases of HSIL. The sensitivity of RCRF was 64.0% for all abnormalities and 75.0% for HSIL compared to the FD. RPS identified an additional 132 (2.15%) abnormal smears, whereas R-10% and RCRF identified an additional 7 (0.11%) and 32 (0.52%), respectively. In conclusion, RPS is an effective method of internal quality control and has better sensitivity than R-10% and RCRF for the detection of FN results. It also allows the FN rate of the laboratory to be monitored and permits continuous evaluation of the prescreening cytologist and the routine screening cytologist. / O exame citopatológico é um método eficiente para prevenir o câncer do colo do útero, no entanto, apresenta altas taxas de resultados falso-negativos (RFN). Para reduzir os RFN, são necessárias medidas de controle interno e externo da qualidade na rotina dos laboratórios. O método de revisão aleatória de 10% dos esfregaços negativos (R-10%) é o mais utilizado, no entanto, não é eficiente para reduzir os RFN. Porém, há evidências de que a revisão dos esfregaços selecionados por critérios clínicos de risco (RCCR) e o pré-escrutínio rápido (PER) apresentam bons resultados. Esse estudo comparou o desempenho do PER, R-10% e RCCR como métodos de controle interno da qualidade dos esfregaços cervicais. A casuística foi constituída por 6.135 esfregaços citopatológicos cervicais de mulheres atendidas nas Unidades Básicas de Saúde de Goiânia GO, no período de março de 2006 a março de 2007. Os resultados citopatológicos foram classificados de acordo com o Sistema de Bethesda 2001. Inicialmente 6.135 esfregaços foram submetidos ao PER e em seguida ao escrutínio de rotina (ER). Após o ER os esfregaços classificados como negativos foram selecionados com base em critérios clínicos de risco e aleatoriamente 10% do total de esfregaços e submetidos às respectivas revisões. Quatro citologistas foram responsáveis pelo PER, ER, R-10% e RCCR e três pelas revisões dos esfregaços alterados e discordantes em qualquer revisão. Os esfregaços com resultados negativos no PER, ER, R-10% e RCCR foram considerados diagnóstico final (DF). Os esfregaços com resultados suspeitos ou insatisfatórios, pelo PER, foram analisados separadamente por dois outros citologistas. Também os esfregaços cujos resultados foram considerados alterados ou insatisfatórios pelo ER, R-10% e/ou RCCR foram igualmente revisados. Quando os dois citologistas revisores emitiram diagnósticos concordantes estes foram considerados DF. Os resultados discordantes foram analisados por um terceiro citologista e em uma reunião de consenso foi definido o DF. Todas as etapas do estudo foram realizadas às cegas, exceto na reunião de consenso. Os esfregaços classificados como negativos pelo ER que foram suspeitos pelo PER e/ou alterados nas R-10% e RCCR e confirmados pelo DF foram considerados RFN. Dos 6.135 esfregaços, 5.522 foram classificados como negativos, 84 como insatisfatórios e 529 como alterados pelo DF. A sensibilidade do PER foi de 63,0% para todas as anormalidades e de 96,7% para lesão intra-epitelial escamosa de alto grau (HSIL) quando comparado ao ER. A sensibilidade do PER foi de 74,9% para todas as anormalidades e de 95,0% para HSIL quando comparado ao DF. A sensibilidade da R-10% foi de 53,8% para todas as anormalidades quando comparado ao DF e não detectou nenhuma HSIL, enquanto a sensibilidade da RCCR foi de 64,0% para todas as anormalidades e de 75,0% para HSIL quando comparado ao DF. O PER acrescentou 132 (2,15%) esfregaços alterados, enquanto que a R-10% e a RCCR acrescentaram sete (0,11%) e 32 (0,52%), respectivamente. Enfim, o PER é uma alternativa eficiente de controle interno da qualidade, apresentando maior sensibilidade que as R-10% e RCCR na detecção de RFN. Permite, ainda, monitorar a taxa de RFN do laboratório, assim como avaliar continuamente o desempenho tanto do pré-escrutinador quanto do escrutinador de rotina.

Pas de résumé en français / Malaria is a devastating global health problem that affected 219 million people and caused 660,000 deaths in 2010. Inaccurate estimation of the level of infection may have adverse clinical and therapeutic implications for patients, and for epidemiological endpoint measurements. The level of infection, expressed as the parasite density (PD), is classically defined as the number of asexual parasites relative to a microliter of blood. Microscopy of Giemsa-stained thick blood smears (TBSs) is the gold standard for parasite enumeration. Parasites are counted in a predetermined number of high-power fields (HPFs) or against a fixed number of leukocytes. PD estimation methods usually involve threshold values; either the number of leukocytes counted or the number of HPFs read. Most of these methods assume that (1) the distribution of the thickness of the TBS, and hence the distribution of parasites and leukocytes within the TBS, is homogeneous; and that (2) parasites and leukocytes are evenly distributed in TBSs, and thus can be modeled through a Poisson-distribution. The violation of these assumptions commonly results in overdispersion. Firstly, we studied the statistical properties (mean error, coefficient of variation, false negative rates) of PD estimators of commonly used threshold-based counting techniques and assessed the influence of the thresholds on the cost-effectiveness of these methods. Secondly, we constituted and published the first dataset on parasite and leukocyte counts per HPF. Two sources of overdispersion in data were investigated: latent heterogeneity and spatial dependence. We accounted for unobserved heterogeneity in data by considering more flexible models that allow for overdispersion. Of particular interest were the negative binomial model (NB) and mixture models. The dependent structure in data was modeled with hidden Markov models (HMMs). We found evidence that assumptions (1) and (2) are inconsistent with parasite and leukocyte distributions. The NB-HMM is the closest model to the unknown distribution that generates the data. Finally, we devised a reduced reading procedure of the PD that aims to a better operational optimization and a practical assessing of the heterogeneity in the distribution of parasites and leukocytes in TBSs. A patent application process has been launched and a prototype development of the counter is in process.