Thesis (Ph. D.)--University of Michigan.

Thesis (Ph. D.)--University of Michigan.

No description available.

<p>We developed a mathematical model to investigate the transmission dynamics of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Our main model is built on the Susceptible-Exposed-Infected-Recovered framework to account for the unique characteristics of COVID-19. In a particular case of the main model, we assessed the optimal allocation of resources to mitigate the spread of the virus. Additionally, we expanded the main model to include another vaccination compartment to explore the strategic distribution of vaccinations. Our findings provided insights into the management of COVID-19 and could guide evidence-based decision-making for public health authorities.</p>

No description available.

This research aims at exploring the existence of a relationship between the use of multimedia in teaching and instructional design guidelines (IDG). An ontology of types of media and teaching methods was developed. Semi-structured interviews have been conducted with 20 instructors. Qualitative and quantitative methodologies were employed. While these are results from a pilot study with a small sample, the analyses suggests a relationship between the use of media in teaching and IDG that is influenced by years of teaching experience and field of study (i.e., Social Sciences). The instructors’ self-assessment of IDG and media usage was not reliable and further validation of a self-assessment instrument is needed. This pilot study demonstrates the feasibility of the methodology which can be used in future research with more participants. / Graduate

A simultaneous survey of canine and human gastrointestinal (GI) parasites was conducted in three socioeconomically disadvantaged, tea-growing communities in Assam, India. The aims of this study were to determine the epidemiology of GI parasites of zoonotic significance in dogs and geohelminth infection in humans using a combination of molecular biological and classical parasitological and epidemiological tools. A total of 328 and 101 dogs participated in the study. The prevalence of GI parasites in dogs was 99%. Parasitic stages presumed to be host-specific for humans such as Ascaris spp., Trichuris trichiura and Isospora belli were also encountered in dog faeces. A polymerase chain reaction - linked restriction fragment length polymorphism (PCRRFLP) was developed to identify the species of Ascaris eggs in dog faeces. The results supported the dog's role as a significant disseminator and environmental contaminator of Ascaris lumbricoides, in communities where promiscuous defecation by humans exist. The prevalence, intensity and associated risk factors for infection with Ascaris, hookworms and Trichuris were also determined among the human population. The overall prevalence of Ascaris was 38% and 43% for both hookworms and Trichuris. The strongest predictors for the intensity of geohelminths included socioeconomic status, age, household crowding, level of education and lack of footwear when outdoors. The zoonotic potential of canine Giardia was investigated by genetically characterising G. duodenalis isolates recovered from humans and dogs at three different loci. Phylogenetic analysis placed canine Giardia isolates within the genetic groupings of human isolates. Further evidence for zoonotic transmission was supported by strong epidemiological data. A highly sensitive and specific PCR RFLP based test was developed to detect and differentiate the species of canine hookworms directly from eggs in faeces. Thirty-six percent of dogs were found to harbour single infections with A. caninum, 24% single infections with A. braziliense and 38% mixed infections with both species. This newly developed PCR-based test provided a rapid, highly sensitive and specific tool for the epidemiological screening of canine Ancylostoma species in a community. A combination of canine population management, effective anthelmintic regimes and improvements in health education and sanitation is recommended for the control of canine and human gastrointestinal parasites in these communities.

O objetivo do trabalho foi descrever, em uma perspectiva histÃrica, o perfil epidemiolÃgico da peste no Estado do Cearà a partir de 1900 e a evoluÃÃo das aÃÃes de controle desse agravo no perÃodo de 1980 a 2008. Realizou-se um estudo descritivo, de natureza histÃrica, com associaÃÃo da abordagem da histÃria oral, para construÃÃo dos cenÃrios epidemiolÃgicos e operacionais e uma revisÃo de informaÃÃes histÃrico-epidemiolÃgicas do programa de controle. Para consubstanciar as informaÃÃes obtidas, foram realizadas entrevistas abertas com especialistas na Ãrea. Os registros histÃricos dos casos humanos foram recuperados somente a partir de 1935 e perÃodos de intensa atividade e outros de quiescÃncia foram identificados. Destaca-se que na dÃcada de 1980 a peste persistiu, atà 1986, de forma endÃmica na Serra da Ibiapaba. No perÃodo de 1982 a 1985 ocorreu um surto na Serra de Baturità tendo sido confirmados 89 casos humanos, registrada elevada densidade populacional de roedores e verificado considerÃvel incremento das aÃÃes do programa. Na dÃcada de 1990 apenas trÃs casos humanos foram confirmados na Serra da Ibiapaba e em 2005 mais um caso foi confirmado na Serra da Pedra Branca. O declÃnio dos casos humanos a partir de 1986 levou à reduÃÃo de todas as aÃÃes. Por vÃrias dÃcadas as aÃÃes do Programa de Controle da Peste (PCP) incluÃam educaÃÃo em saÃde, busca ativa de atividade pestosa e coleta de espÃcimes para anÃlises bacteriolÃgicas e sorolÃgicas. InquÃritos sorolÃgicos em carnÃvoros domÃsticos (cÃes e gatos) predadores de roedores foram introduzidos na rotina do PCP em 1989 visando o monitoramento da circulaÃÃo da Y. pestis e se revelou a ferramenta mais eficaz para detecÃÃo da atividade da zoonose. Foram detectados picos de positivaÃÃo em 1997, 2001 e 2005, e mesmo assim essa atividade vem sendo enfraquecida no estado e a recomendaÃÃo atual à restringir os inquÃritos sorolÃgicos apenas a amostras caninas. Os focos do Cearà estÃo localizados nos complexos ecolÃgicos das Serras de BaturitÃ, do Machado, das Matas, da Pedra Branca, de Uruburetama, da Ibiapaba e Chapada do Araripe. As aÃÃes inicialmente desenvolvidas nos focos como unidade ecolÃgica, apÃs a divisÃo polÃtico/administrativa das Ãreas, com a descentralizaÃÃo, passaram a ser organizadas em nÃvel de Regionais. Os focos do Cearà destacam-se como os mais importantes no Brasil, tanto pela ocorrÃncia de casos humanos quanto pela evidÃncia de circulaÃÃo permanente da bactÃria. A persistÃncia da peste no estado deve, pois, ser considerada uma ameaÃa real e permanente de acometimento humano nessas regiÃes, que pode estender-se para outros lugares, inclusive centros urbanos, tornando-se imperativo que os profissionais de saÃde estejam preparados. Por isso, para garantir o monitoramento dos focos na totalidade, torna-se imprescindÃvel a manutenÃÃo da vigilÃncia na perspectiva de foco, para permitir a adoÃÃo de medidas de controle adequadas para proteÃÃo das populaÃÃes humanas nas Ãreas focais. / Our objective was to describe, in a historical perspective, the epidemiological profile of plague in the State of Cearà since 1900 and the evolution of the activities of the disease control from 1980 to 2008. We carried out a descriptive study using an historical approach based on the oral history for the construction of epidemiological and operational scenarios and a review of the historical and epidemiological information about the plague control program. To strengthen the information obtained, we conducted interviews with experts in the area. Historical records of human cases have been recovered only from 1935, and periods of intense activity and others of quiescence were identified. It is noteworthy that in the years 1980 plague persisted as endemic in Serra da Ibiapaba until 1986. In the period from 1982 to 1985 there was an outbreak in Serra de Baturità with 89 confirmed human cases; a rise of the rodentsâ population and significant increasing in the activities of the program were observed. In the 1990s, only three human cases were confirmed in Serra da Ibiapaba and in 2005 another case was confirmed in Serra da Pedra Branca. The decline of human cases after 1986 led to the reduction of the program activities. For several decades the activities of the Plague Control Program (PCP) included health education, active search for plague activity and collection of specimens for bacteriological and serological analysis. Serological surveys in domestic carnivores (dogs and cats) predators of rodents were introduced into the routine of PCP in 1989 to monitor Y. pestis activities in the foci proving the most effective tool to detect the zoonosis activities in the foci. In spite of the occurrence of positivity peaks detected in 1997, 2001 and 2005, this activity has been diminished in the state and the present recommendation is to restrict the serological surveys to canine samples only. The Cearà foci are located in the ecological complexes of the âserrasâ BaturitÃ, Machado, Matas, Pedra Branca, Uruburetama, Ibiapaba and Araripe. The foci area were formerly dealt as ecological units; however after the political/administrative division of the areas, in view of the âdecentralization processâ, they are now scattered among the âRegionaisâ. The Cearà foci are among the most important in Brazil, both by the number of human cases and by evidence of the permanent circulation of the bacterium. The persistence of plague in the state should therefore be considered a real and permanent risk in these regions, which may extend to other places, including urban centers, making it imperative that health professionals are prepared. Therefore, to ensure the monitoring of the foci, it is essential to maintain surveillance under the ecological approach, to enable the adoption of appropriate control measures for protection of human populations in focal areas.

Philosophiae Doctor - PhD / Epidemiological studies have highlighted that leukaemia can be considered as the most prominent malignancy after radiation exposure during childhood. The lifetime risk on radiation-induced leukaemia for a given dose is 3 – 5 times higher for children compared to adults. The high risk at a young age is related to the elevated sensitivity of the red bone marrow where haematopoietic stem and progenitor cells (HSPCs) are located. HSPCs self-renewal capacity and long-life span increase their susceptibility to DNA damage accumulation, making them a major target of radiation-induced carcinogenesis. Proton beam therapy (PBT) is increasingly used to treat paediatric brain tumours due to its dose sparing properties compared to conventional X-ray based radiotherapy. However, concerns regarding the carcinogenic potential of secondary neutrons produced during PBT, especially in terms of their effect on HSPCs harboured in the cranial bone marrow of paediatric patients, remain. In this study, the radiobiological differences between 60Co γ-rays and p(66)/Be(40) neutron exposure was investigated to resolve the underlying mechanisms for the high radiosensitivity of HSPCs (CD34+ cells) isolated from umbilical cord blood (UCB). For both radiation qualities, an apparent dose-dependent increase in the frequency of radiation-induced MN was observed in CD34+ cells. Furthermore, increased cytogenetic damage was observed with the CBMN assay after neutron irradiation, which highlights its leukaemogenic potential. In addition, no difference was observed in the nuclear division index of the CD34+ cells post-irradiation between both radiation qualities. The number of DNA DSBs was assessed by microscopic scoring of γ-H2AX foci, 2 and 18 hours after radiation exposure. A significant higher number of DNA DSBs were observed 2 hours after neutron irradiation with 0.5 Gy, but decreased to similar levels for both radiation qualities after 18 hours. Different stages of apoptosis in CD34+ cells were studied at 18 and 42 hours numerous time points post-irradiation by flow cytometry using the Annexin/PI assay. In contrast to the γ-H2AX foci results, a significant difference in late apoptosis was observed at 18 hours and 42 hours between the two radiation qualities. The results point towards a fast error-prone DNA repair in HSPCs after neutron irradiation, which might contribute to genomic instability and leukemogenesis. In the second phase of the PhD project, the impact of age on radiosensitivity was investigated by comparing newborn T-lymphocytes with adult peripheral blood (APB) T-lymphocytes. The major difference between UCB and APB T-lymphocytes, is their immunophenotypic profile. Since it is known that different T-lymphocyte subsets have a difference in radiosensitivity, the fraction of CD4+, CD8+, naïve (CD45RA+) and memory (CD45RO+) T-lymphocytes was determined via flow cytometry in the two groups. The cytokinesis-block micronucleus (CBMN) assay was used to determine the extent to which age influences the frequency of cytogenic damage in response to 60Co γ-rays radiation. For both APB and UCB, an outspoken dose-dependent increase in the frequency of radiation-induced MN was observed at 0.5, 1, 3 and 4 Gy. However, no significant difference was observed at 4 Gy when comparing MN yields of APB and UCB. An increased radiosensitivity of newborn to adult donors of 34%, 42%, 29%, 26% and 16% was observed based on the MN scoring at doses of 0.5, 1, 2, 3 and 4 Gy, respectively. The lowest radiosensitivity was identified at the highest dose, which might explain the non-significant difference at 4 Gy. In addition, there was a clear trend that females were more sensitive to 60Co γ-rays radiation than males in both adults and newborns, even though the difference was not significant. The immunophenotypic study revealed that that both the CD4+ and CD8+ T-lymphocytes of newborns are mainly naïve. This is illustrated by the co-expression of CD45RA+ on 90.70% (range: 80.80% – 98.40%) and 95.90% (range: 89.60% – 98.80%) of CD4+ and CD8+ cells respectively. The composition of adult T-lymphocytes, in contrast, is clearly different with a more equal distribution between CD45RA+ and CD45RO+ subpopulations. This finding demonstrates that there are differences in the radiosensitivity between newborn and adult T-lymphocytes which might be linked to the immunophenotypic change of T-lymphocytes with age.

Κατά τη χρονική περίοδο 2006-2007 απομονώθηκαν συνολικά 952 στελέχη P. aeruginosa στο Μικροβιολογικό Εργαστήριο του ΠΓΝΠ. Επιλέχθηκαν για μελέτη 240 στελέχη, τα πρώτα δέκα από κάθε μήνα και ένα στέλεχος από κάθε ασθενή. Τα στελέχη απομονώθηκαν μετά από καλλιέργεια κλινικών δειγμάτων: τραυμάτων-υγρών, κεντρικών φλεβικών καθετήρων, αναπνευστικού συστήματος, ούρων, κοπράνων και αίματος. Τα κλινικά δείγματα προέρχονταν από ασθενείς που νοσηλεύονταν στη ΜΕΘ, τις Παθολογικές Κλινικές, τις Χειρουργικές Κλινικές, την Παιδιατρική Κλινική και προσέρχονταν στα Εξωτερικά Ιατρεία του ΠΓΝΠ. Φαινοτυπικές και μοριακές μεθόδοι χρησιμοποιήθηκαν για την επιδημιολογική διερεύνηση των στελεχών. Ανιχνεύθηκε ο βιότυπος, έγινε έλεγχος της ευαισθησίας στα αντιβιοτικά, έλεγχος της παραγωγής MBLs και ορολογική τυποποίηση των στελεχών. Οι μοριακές μέθοδοι περιλάμβαναν την ανίχνευση των γονιδίων blaVIM, exoY, exoT, exoS και exoU με PCR, τυποποίηση του γονιδίου blaVIM με ανάλυση της αλληλουχίας και εφαρμογή των μεθόδων PFGE (SpeI) και MLST ταυτοποίηση κλώνων. Τα περισσότερα στελέχη εμπλέκονταν σε λοιμώξεις (65,42%). Τα περισσότερα δείγματα προήλθαν από τη ΜΕΘ (92/240, 38%), σημαντικό ποσοστό των οποίων αφορούσε τη χλωρίδα των ασθενών (56/92, 61%). Τα περισσότερα στελέχη ήταν MDRPA (63,33%) και άνηκαν στον ορότυπο Ο11 (49,16%). Το 33% των ιμιπενέμη ανθεκτικών στελεχών ήταν blaVIM θετικά (κυρίως blaVIM2, και blaVIM1). Με την PFGE τα στελέχη διακρίθηκαν σε 5 κύριους τύπους a, d, b, c και s, με επικρατούντες τους a (33,75%) και d (13,75%). Με την MLST τα στελέχη διακρίθηκαν κυρίως στους δύο παγκόσμιους κλώνους ST235 (PFGE τύποι a, d και b) και ST111 (PFGE τύπος b). Η παρούσα μελέτη αναδεικνύει μία επιδημική έξαρση από MDRPA στο ΠΓΝΠ. Τα MDRPA ανήκαν κυρίως στους PFGE τύπους a και d του ορότυπου Ο11 και κλώνου ST235, με γονοτυπικό προφίλ exoU +/exoS - που επικρατούσαν στη ΜΕΘ. Η παρατήρηση ότι τα περισσότερα στελέχη που απομονώθηκαν από δείγματα αποικισμού των ασθενών (49/83) ανήκαν στον κλώνο ST235 υποδεικνύει ότι ο αποικισμός των ασθενών της ΜΕΘ συμβάλλει στη λοίμωξη από στελέχη P. aeruginosa και στη διασπορά τους στις άλλες κλινικές του νοσοκομείου. Το γεγονός ότι τα περισσότερα των στελεχών (18/33) του PFGE τύπου d (ST235) φέρουν το γονίδιο blaVIM2 ενισχύει την άποψη ότι η κλωνική διασπορά διαδραμάτισε ρόλο στην επιδημική έξαρση από ιμιπενέμη-ανθεκτικά στελέχη P. aeruginosa. / During the period 2006-2007 a total of 952 P. aeruginosa strains were isolated in the Microbiology Laboratory of the University Hospital of Patras. Two hundred and forty, the first ten from every month no replicate isolates (one isolate per patient), were selected to be studied further. The strains were isolated after inoculation of clinical specimens: wound-liquids, intravenous catheters, respiratory samples, urine, stool and blood. P. aeruginosa was identified by standard phenotypic methods. The clinical samples were collected from patients hospitalized in the ICU, Internal Medicine, Surgical Units, Pediatric Unit and the Department of Outpatients. Phenotypic and molecular methods were applied for the epidemiological study. Phenotypic methods were: antibiotic susceptibility testing, metallo-beta-lactamases (MBL) production and serotyping. The molecular methods included detection of genes blaVIM, exoY, exoT, exoS, exoU by PCR, blaVIM gene sequencing, PFGE (SpeI) and MLST. The majority of isolates were infection-related (65,42%). Most of them were recovered from ICU patients (92/240, 38%), 61% (56/92) of which were colonizing isolates. Most strains were MDRPA (63,33%) and belonged to serotype O11 (49,16%). Thirty three percent (33%) of imipenem non-susceptible isolates were blaVIM positive (specifically blaVIM2, and blaVIM1). PFGE exhibited five main types: a, d, b, c and s [predominant a (33,75%), d (13,75%)]. By MLST, the strains were classified mainly in the two international clones ST235 (PFGE types a, d and b), and ST111 (PFGE type b). The present study revealed an outbreak of MDRPA in the University Hospital of Patras. MDRPA belonged mainly to PFGE types a and d of serotype O11 and clone ST235, showing the profile exoU +/exoS -, and predominaded in ICU. The observation that most colonizing isolates (49/83) belonged to ST235 indicates that colonization during ICU hospitalization contributes to infection and spread of MDRPA to other wards. The fact that the majority (18/33) of PFGE type d strains (ST235) carry blaVIM2 gene, reinforces that clonal spread may have played a role in the outbreak of imipenem non-susceptible P. aeruginosa strains.