Exploration génétique de l'hypothyroïdie congénitale par dysgénésie thyroïdienne

L'hypothyroïdie congénitale par dysgénésie thyroïdienne (HCDT, ectopie dans plus de 80 %) a une prévalence de 1 cas sur 4000 naissances vivantes. L’HCDT est la conséquence d'une défaillance de la thyroïde embryonnaire à se différencier, à se maintenir ou à migrer vers sa localisation anatomique (partie antérieure du cou), qui aboutit à une absence totale de la thyroïde (athyréose) ou à une ectopie thyroïdienne (linguale ou sublinguale). Les HCDT sont principalement non-syndromiques (soit 98% des cas sont non-familiale), ont un taux de discordance de 92% chez les jumeaux monozygotes, et ont une prédominance féminine et ethnique (i.e., Caucasienne). La majorité des cas d’HCDT n’a pas de cause connue, mais est associée à un déficit sévère en hormones thyroïdiennes (hypothyroïdie). Des mutations germinales dans les facteurs de transcription liés à la thyroïde (NKX2.1, FOXE1, PAX8, NKX2.5) ont été identifiées dans seulement 3% des patients atteints d’HCDT sporadiques et l’analyse de liaisons exclue ces gènes dans les rares familles multiplex avec HCDT. Nous supposons que le manque de transmission familiale claire d’HCDT peut résulter de la nécessité d’au moins deux « hits » génétiques différents dans des gènes importants pour le développement thyroïdien. Pour répondre au mieux nos questions de recherche, nous avons utilisé deux approches différentes: 1) une approche gène candidat, FOXE1, seul gène impliqué dans l’ectopie dans le modèle murin et 2) une approche en utilisant les techniques de séquençage de nouvelle génération (NGS) afin de trouver des variants génétiques pouvant expliquer cette pathologie au sein d’une cohorte de patients avec HCDT. Pour la première approche, une étude cas-contrôles a été réalisée sur le promoteur de FOXE1. Il a récemment été découvert qu’une région du promoteur de FOXE1 est différentiellement méthylée au niveau de deux dinucléotides CpG consécutifs, définissant une zone cruciale de contrôle de l’expression de FOXE1. L’analyse d’association basée sur les haplotypes a révélé qu’un haplotype (Hap1: ACCCCCCdel1C) est associé avec le HCDT chez les Caucasiens (p = 5x10-03). Une réduction significative de l’activité luciférase est observée pour Hap1 (réduction de 68%, p<0.001) comparé au promoteur WT de FOXE1. Une réduction de 50% de l’expression de FOXE1 dans une lignée de cellules thyroïdienne humaine est suffisante pour réduire significativement la migration cellulaire (réduction de 55%, p<0.05). Un autre haplotype (Hap2: ACCCCCCC) est observé moins fréquemment chez les Afro-Américain comparés aux Caucasiens (p = 1.7x10-03) et Hap2 diminue l’activité luciférase (réduction de 26%, p<0.001). Deux haplotypes distincts sont trouvés fréquemment dans les contrôles Africains (Black-African descents). Le premier haplotype (Hap3: GTCCCAAC) est fréquent (30.2%) chez les contrôles Afro-Américains comparés aux contrôles Caucasiens (6.3%; p = 2.59 x 10-9) tandis que le second haplotype (Hap4: GTCCGCAC) est trouvé exclusivement chez les contrôles Afro-Américains (9.4%) et est absent chez les contrôles Caucasiens (P = 2.59 x 10-6). Pour la deuxième approche, le séquençage de l’exome de l’ADN leucocytaire entre les jumeaux MZ discordants n’a révélé aucune différence. D'où l'intérêt du projet de séquençage de l’ADN et l’ARN de thyroïdes ectopiques et orthotopiques dans lesquelles de l'expression monoallélique aléatoire dans a été observée, ce qui pourrait expliquer comment une mutation monoallélique peut avoir des conséquences pathogéniques. Finalement, le séquençage de l’exome d’une cohorte de 36 cas atteints d’HCDT a permis d’identifier de nouveaux variants probablement pathogéniques dans les gènes récurrents RYR3, SSPO, IKBKE et TNXB. Ces quatre gènes sont impliqués dans l’adhésion focale (jouant un rôle dans la migration cellulaire), suggérant un rôle direct dans les défauts de migration de la thyroïde. Les essais de migration montrent une forte diminution (au moins 60% à 5h) de la migration des cellules thyroïdiennes infectées par shRNA comparés au shCtrl dans 2 de ces gènes. Des zebrafish KO (-/- et +/-) pour ces nouveaux gènes seront réalisés afin d’évaluer leur impact sur l’embryologie de la thyroïde.

Further exploration of the Dendritic Cell Algorithm: antigen multiplier and time windows

As an immune-inspired algorithm, the Dendritic Cell Algorithm (DCA), produces promising performance in the field of anomaly detection. This paper presents the application of the DCA to a standard data set, the KDD 99 data set. The results of different implementation versions of the DCA, including antigen multiplier and moving time windows, are reported. The real-valued Negative Selection Algorithm (NSA) using constant-sized detectors and the C4.5 decision tree algorithm are used, to conduct a baseline comparison. The results suggest that the DCA is applicable to KDD 99 data set, and the antigen multiplier and moving time windows have the same effect on the DCA for this particular data set. The real-valued NSA with contant-sized detectors is not applicable to the data set. And the C4.5 decision tree algorithm provides a benchmark of the classification performance for this data set.

Connecting the dots: Examining the role of parental beliefs and preschoolers’ affect and engagement in predicting parent-child number exploration during a meaningful math experience

The current study examined the frequency and quality of how 3- to 4-year-old children and their parents explore the relations between symbolic and non-symbolic quantities in the context of a playful math experience, as well as the role of both parent and child factors in this exploration. Preschool children’s numerical knowledge was assessed while parents completed a survey about the number-related experiences they share with their children at home, and their math-related beliefs. Parent-child dyads were then videotaped playing a modified version of the card game War. Results suggest that parents and children explored quantity explicitly on only half of the cards and card pairs played, and dyads of young children and those with lower number knowledge tended to be most explicit in their quantity exploration. Dyads with older children, on the other hand, often completed their turns without discussing the numbers at all, likely because they were knowledgeable enough about numbers that they could move through the game with ease. However, when dyads did explore the quantities explicitly, they focused on identifying numbers symbolically, used non-symbolic card information interchangeably with symbolic information to make the quantity comparison judgments, and in some instances, emphasized the connection between the symbolic and non-symbolic number representations on the cards. Parents reported that math experiences such as card game play and quantity comparison occurred relatively infrequently at home compared to activities geared towards more foundational practice of number, such as counting out loud and naming numbers. However, parental beliefs were important in predicting both the frequency of at-home math engagement as well as the quality of these experiences. In particular, parents’ specific beliefs about their children’s abilities and interests were associated with the frequency of home math activities, while parents’ math-related ability beliefs and values along with children’s engagement in the card game were associated with the quality of dyads’ number exploration during the card game. Taken together, these findings suggest that card games can be an engaging context for parent-preschooler exploration of numbers in multiple representations, and suggests that parents’ beliefs and children’s level of engagement are important predictors of this exploration.

Mind the gap! An exploration of the role of lifelong learning in promoting co-production and citizenship within social care for older people

Contemporary themes in public policy have emphasised co-productive approaches within both the access and provision of support services to older people. This paper provides a cross disciplinary exploration from its respective authors perspectives on social work and educational gerontology to examine the potential for lifelong learning and learning interventions from which co-production with those using social care services in later life might be better facilitated. Using an example from the UK, we specifically elicit how co-produced care can enhance the horizon of learning and learning research. The synthesis of ideas across these two disciplines could enrich understanding and provide essential levers for moving towards empowerment and emancipation by engaging with a more co-productive approach in social care for older people. (DIPF/Orig.)

Exploration of the dendritic cell algorithm with the duration calculus

As one of the newest members in Articial Immune Systems (AIS), the Dendritic Cell Algorithm (DCA) has been applied to a range of problems. These applications mainly belong to the eld of anomaly detection. However, real-time detection, a new challenge to anomaly detection, requires improvement on the real-time capability of the DCA. To assess such capability, formal methods in the research of real-time systems can be employed. The ndings of the assessment can provide guideline for the future development of the algorithm. Therefore, in this paper we use an interval logic based method, named the Duration Calcu- lus (DC), to specify a simplied single-cell model of the DCA. Based on the DC specications with further induction, we nd that each individual cell in the DCA can perform its function as a detector in real-time. Since the DCA can be seen as many such cells operating in parallel, it is potentially capable of performing real-time detection. However, the analysis process of the standard DCA constricts its real-time capability. As a result, we conclude that the analysis process of the standard DCA should be replaced by a real-time analysis component, which can perform periodic analysis for the purpose of real-time detection.

Scrotal Exploration for Testicular Torsion and Testicular Appendage Torsion: Emergency and Reality

Background: Scrotal exploration is considered the procedure of choice for acute scrotum. Objectives: We evaluated the importance of early diagnosis and testicular salvage on the therapeutic outcomes of patients with pediatric testicular torsion (TT) and testicular appendage torsion (TAT) in our geographic area. Patients and Methods: We performed a retrospective database analysis of patients who underwent emergency surgery for TT or TAT between January 1996 and June 2009. Patient history, physical examination findings, laboratory test results, color Doppler sonography (CDS) results, and surgical findings were reviewed. Results: A total of 65 cases were included in our analysis. Forty-two cases were followed up for at least 3 months. Testicular tenderness was identified as the major clinical manifestation of TT, while only a few patients with TAT presented with swelling. CDS was an important diagnostic modality. The orchiectomy rate was 71% in the TT group. Conclusions: Cases of acute scrotum require attention in our area. Early diagnosis and scrotal exploration could salvage the testis or preserve normal function without the need for surgery.

Outcomes of Second Look Exploration in Testicular Torsion of Children

Background: Testicular torsion (TT), or twisting of the testicle resulting in a strangulation of the blood supply, occurs in men whose tissue surrounding the testicle is not well attached to the scrotum. It is important to emphasize that testicular torsion is a medical emergency. Objectives: The aim of this study is to evaluate the second look exploration and outcomes in TT. Patients and Methods: Seventy boys out of 124 patients underwent early exploration and 48 hours later second look exploration due to TT. All patients were checked with preoperative color-doppler ultrasonography (CDU) and intraoperative bleeding test. Data included age at admission, side of pathology, relation of TT with season of year, duration of preoperative history, degree of testicular torsion, CDU findings, and degree of bleeding; results of second look exploration, follow-up, and outcomes were analyzed. Results: Totally 70 patients were included in this study within five years, of which mean age was 28.6 ± 32.9 months (range 1 to 144), 48% of our patients had nausea and vomiting. Preoperative CDU showed absent/weak flow in 50 (71%) cases. Winter showed most frequently (44%) referred cases of testicular torsion. Orchidopexy was performed in 44 (63%) and orchidectomy in 26 (37%) cases after second look exploration. Mean follow-up duration was 3.1 ± 1.4 years. 4 (9%) cases in orchidopexy group developed testicular atrophy during follow-up, all four cases had a history of longer than 12 hours and grade II testicular bleeding test intra-operatively. Other orchidopexy patients salvaged. 26 patients, who were in grade III, underwent orchidectomy in second look exploration. Conclusions: TT requires emergency attention. The ischemia time of the testis is traditionally after 6 hours, and imaging or other diagnostic modality should not be a cause of delay. Early surgical exploration is modality of choice, and second look exploration after 48 hours can be more effective and salvageable in these patients.

Exploration of Ground Penetrating Radar and Time Domain Reflectometry Methods for the Determination of Pavement Dielectric Constant

Traditionally, densities of newly built roadways are checked by direct sampling (cores) or by nuclear density gauge measurements. For roadway engineers, density of asphalt pavement surfaces is essential to determine pavement quality. Unfortunately, field measurements of density by direct sampling or by nuclear measurement are slow processes. Therefore, I have explored the use of rapidly-deployed ground penetrating radar (GPR) as an alternative means of determining pavement quality. The dielectric constant of pavement surface may be a substructure parameter that correlates with pavement density, and can be used as a proxy when density of asphalt is not known from nuclear or destructive methods. The dielectric constant of the asphalt can be determined using ground penetrating radar (GPR). In order to use GPR for evaluation of road surface quality, the relationship between dielectric constants of asphalt and their densities must be established. Field measurements of GPR were taken at four highway sites in Houghton and Keweenaw Counties, Michigan, where density values were also obtained using nuclear methods in the field. Laboratory studies involved asphalt samples taken from the field sites and samples created in the laboratory. These were tested in various ways, including, density, thickness, and time domain reflectometry (TDR). In the field, GPR data was acquired using a 1000 MHz air-launched unit and a ground-coupled unit at 200 and 500 MHz. The equipment used was owned and operated by the Michigan Department of Transportation (MDOT) and available for this study for a total of four days during summer 2005 and spring 2006. The analysis of the reflected waveforms included “routine” processing for velocity using commercial software and direct evaluation of reflection coefficients to determine a dielectric constant. The dielectric constants computed from velocities do not agree well with those obtained from reflection coefficients. Perhaps due to the limited range of asphalt types studied, no correlation between density and dielectric constant was evident. Laboratory measurements were taken with samples removed from the field and samples created for this study. Samples from the field were studied using TDR, in order to obtain dielectric constant directly, and these correlated well with the estimates made from reflection coefficients. Samples created in the laboratory were measured using 1000 MHz air-launched GPR, and 400 MHz ground-coupled GPR, each under both wet and dry conditions. On the basis of these observations, I conclude that dielectric constant of asphalt can be reliably measured from waveform amplitude analysis of GJPR data, based on the consistent agreement with that obtained in the laboratory using TDR. Because of the uniformity of asphalts studied here, any correlation between dielectric constant and density is not yet apparent.

A Longitudinal Exploration of the Relationship Between Oral Reading Fluency and Reading Comprehension Achievement Among a Sample of Diverse Young Learners

Exploring the relationship between early oral reading fluency ability and reading comprehension achievement among an ethnically and racially diverse sample of young learners from low-income families, attending elementary school within a large public school district in southeast Florida is the purpose of this longitudinal study. Although many studies have been conducted to address the relationship between oral reading fluency ability and reading comprehension achievement, most of the existing research failed either to disaggregate the data by demographic subgroups or secure a large enough sample of students to adequately represent the diverse subgroups. The research questions that guided this study were: (a) To what extent does early oral reading fluency ability measured in first, second, or third grade correlate with reading comprehension achievement in third grade? (b) To what extent does the relationship of early oral reading fluency ability and reading comprehension achievement vary by demographic subgroup membership (i.e., gender, race/ethnicity, socioeconomic status) among a diverse sample of students? A predictive research design using archived secondary data was employed in this nonexperimental quantitative methods study of 1,663 third grade students who attended a cohort of 25 Reading First funded schools. The data analyzed derived from the Dynamic Indicators of Basic Early Literacy Skills Oral Reading Fluency (DIBELS ORF) measure administered in first, second, and third grades and the Florida Comprehensive Assessment Test of the Sunshine State Standards (FCAT-SSS) Reading administered in third grade. Linear regression analyses between each of the oral reading fluency and reading comprehension measures produced significant positive correlations. Hierarchical regression analyses supported the predictive potential of all three oral reading fluency ability measures toward reading comprehension achievement, with the first grade oral reading fluency ability measure explaining the most significant variance in third grade reading comprehension achievement. Male students produced significant overall differences in variance when compared to female students as did the Other student subgroup (i.e., Asian, Multiracial, and Native American) when compared to Black, White, and Hispanic students. No significant differences in variance were produced between students from low and moderate socioeconomic families. These findings are vital toward adding to the literature of diverse young learners.

Gaining Insight into Teaching: A Phenomenological Exploration of the Lived Experience of the Teachers of the Year

What qualities, skills, and knowledge produce quality teachers? Many stake-holders in education argue that teacher quality should be measured by student achievement. This qualitative study shows that good teachers are multi-dimensional; their effectiveness cannot be represented by students’ test scores alone. The purpose of this phenomenological study was to gain a deeper understanding of quality in teaching by examining the lived experiences of 10 winners or finalists of the Teacher of the Year (ToY) Award. Phenomenology describes individuals’ daily experiences of phenomena, examines how these experiences are structured, and focuses analysis on the perspectives of the persons having the experience (Moustakas, 1994). This inquiry asked two questions: (a) How is teaching experienced by recognized as outstanding Teachers of the Year? and (b) How do ToYs feelings and perceptions about being good teachers provide insight, if any, about concepts such as pedagogical tact, teacher selfhood, and professional dispositions? Ten participants formed the purposive sample; the major data collection tool was semi-structured interviews (Patton, 1990; Seidman, 2006). Sixty to 90-minute interviews were conducted with each participant. Data also included the participants’ ToY application essays. Data analysis included a three-phase process: description, reduction, interpretation. Findings revealed that the ToYs are dedicated, hard-working individuals. They exhibit behaviors, such as working beyond the school day, engaging in lifelong learning, and assisting colleagues to improve their practice. Working as teachers is their life’s compass, guiding and wrapping them into meaningful and purposeful lives. Pedagogical tact, teacher selfhood, and professional dispositions were shown to be relevant, offering important insights into good teaching. Results indicate that for these ToYs, good teaching is experienced by getting through to students using effective and moral means; they are emotionally open, have a sense of the sacred, and they operate from a sense of intentionality. The essence of the ToYs teaching experience was their being properly engaged in their craft, embodying logical, psychological, and moral realms. Findings challenge current teacher effectiveness process-product orthodoxy which makes a causal connection between effective teaching and student test scores, and which assumes that effective teaching arises solely from and because of the actions of the teacher.

Workplace aggression: A reconceptualization of the construct & an exploration of strain based outcomes

The examination of Workplace Aggression as a global construct conceptualization has gained considerable attention over the past few years as organizations work to better understand and address the occurrence and consequences of this challenging construct. The purpose of this dissertation is to build on previous efforts to validate the appropriateness and usefulness of a global conceptualization of the workplace aggression construct. ^ This dissertation has been broken up into two parts: Part 1 utilized a Confirmatory Factor Analysis approach in order to assess the existence of workplace aggression as a global construct; Part 2 utilized a series of correlational analyses to examine the relationship between a selection of commonly experienced individual strain based outcomes and the global construct conceptualization assessed in Part 1. Participants were a diverse sample of 219 working individuals from Amazon’s Mechanical Turk participant pool. ^ Results of Part 1 did not show support for a one-factor global construct conceptualization of the workplace aggression construct. However, support was shown for a higher-order five-factor model of the construct, suggesting that it may be possible to conceptualize workplace aggression as an overarching construct that is made up of separate workplace aggression constructs. Results of Part 2 showed support for the relationships between an existing global construct workplace aggression conceptualization and a series of strain-based outcomes. Utilizing correlational analyses, additional post-hoc analyses showed that individual factors such as emotional intelligence and personality are related to the experience of workplace aggression. Further, utilizing moderated regression analysis, the results demonstrated that individuals experiencing high levels of workplace aggression reported higher job satisfaction when they felt strongly that the aggressive act was highly visible, and similarly, when they felt that there was a clear intent to cause harm. ^ Overall, the findings of this dissertation do support the need for a simplification of its current state of measurement. Future research should continue to examine workplace aggression in an effort to shed additional light on the structure and usefulness of this complex construct.^

A Phenomenological Exploration of Black Male Law Enforcement Officers' Perspectives of Racial Profiling and Their Law Enforcement Career Exploration and Commitment

This phenomenological study explored Black male law enforcement officers’ perspectives of how racial profiling shaped their decisions to explore and commit to a law enforcement career. Criterion and snow ball sampling was used to obtain the 17 participants for this study. Super’s (1990) archway model was used as the theoretical framework. The archway model “is designed to bring out the segmented but unified and developmental nature of career development, to highlight the segments, and to make their origin clear” (Super, 1990, p. 201). Interview data were analyzed using inductive, deductive, and comparative analyses. Three themes emerged from the inductive analysis of the data: (a) color and/or race does matter, (b) putting on the badge, and (c) too black to be blue and too blue to be black. The deductive analysis used a priori coding that was based on Super’s (1990) archway model. The deductive analysis revealed the participants’ career exploration was influenced by their knowledge of racial profiling and how others view them. The comparative analysis between the inductive themes and deductive findings found the theme “color and/or race does matter” was present in the relationships between and within all segments of Super’s (1990) model. The comparative analysis also revealed an expanded notion of self-concept for Black males – marginalized and/or oppressed individuals. Self-concepts, “such as self-efficacy, self-esteem, and role self-concepts, being combinations of traits ascribed to oneself” (Super, 1990, p. 202) do not completely address the self-concept of marginalized and/or oppressed individuals. The self-concept of marginalized and/or oppressed individuals is self-efficacy, self-esteem, traits ascribed to oneself expanded by their awareness of how others view them. (DuBois, 1995; Freire, 1970; Sheared, 1990; Super, 1990; Young, 1990). Ultimately, self-concept is utilized to make career and life decisions. Current human resource policies and practices do not take into consideration that negative police contact could be the result of racial profiling. Current human resource hiring guidelines penalize individuals who have had negative police contact. Therefore, racial profiling is a discriminatory act that can effectively circumvent U.S. Equal Employment Opportunities Commission laws and serve as a boundary mechanism to employment (Rocco & Gallagher, 2004).

An exploration of students’ perceptions and attitudes towards creativity in engineering education

Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2016-09-29 17:45:16.051