Most in vitro systems employ the standard cell culture maintenance conditions of 95 % air with 5 % CO2 to balance medium pH, which translates to culture oxygen tensions of approximately 20 % - above the typical ≤ 6 % found in most tissues. The current investigation, therefore, aims to characterize the effect of maintenance and toxicant exposure with a particular focus on the α,β-unsaturated aldehyde, acrolein, in the presence of physiologically relevant oxygen tension using a differentiated H9c2 cardiomyoblast subclone. H9c2 cells were maintained separately in 20.1 and 5 % oxygen, after which cells were differentiated for five days, and then exposed to acrolein in media containing varying concentrations of tricarboxylic acid and glycolytic substrates. Cells were then assessed for viability and metabolism via the MTT conversion assay. H9c2 cells were assessed for mechanistic elucidation to characterize contributors to cellular death, including mitochondrial membrane potential (ΔΨm) reductions (JC-1), intracellular calcium influx (Fluo-4), and PARP activation. Exposure to acrolein in differing oxygen tensions revealed that standard culture cells are particularly sensitive to acrolein, but cells cultured in 5 % oxygen, depending on the medium pyruvate concentration, can be rescued significantly. Further, reductions in ΔΨm were reversed by co-exposure of 5-10 mM EGTA for both culture conditions, while intracellular calcium transients were noted only for standard cultures. The results demonstrate significant metabolic reprogramming which desensitizes differentiated H9c2 to acrolein-induced cytotoxicity. Further, PARP and extracellular calcium contribute to the fate of these cells exposed to acrolein, though clotrimazole-associated TRPM2 channels may not be significantly involved. Conclusively, significant alteration of toxicogenic response was noted in this cell line when cultured under physiologically relevant conditions, and may have a substantial impact on the reliability and predictive power and interpretive application of in vitro-based toxicity models cultured under standard culture conditions, depending on the parent tissue.

South Africa has the largest number of people living with HIV and the largest HIV treatment program in the world, supplying antiretroviral therapy (ART) to 66% of the 7.6 million people living with HIV in the country in 2019. To reach the remaining 34%, the already overburdened health system needs to find ways of attracting and retaining groups at higher risk of attrition and optimizing convenience for providers and patients. We identified three examples of “differentiated service delivery”, an approach that adapts HIV services to patient and health system needs: (1) male clinics, attended and staffed exclusively by men, (2) youth clinics, exclusively for youth aged 12–25, offering flexible hours and youth-targeted services and (3) a pharmacy-led fast-track ART refill program where stable ART patients can pick up medication without seeing a clinician. We explore attrition (defined as death or loss to follow-up at end of follow-up time) in these services using data from a large, established HIV cohort in Khayelitsha, a high HIV-prevalence, low-income area in South Africa. The first study examines whether males attending two male clinics (Male Clinic 1 and Male Clinic 2) show lower attrition compared to those attending general primary healthcare clinics. Using exposure propensity scores, we matched male clinic patients 1:1 to males at other clinics and used Cox proportional hazards regression to estimate the association between attrition and attending a male clinic. In the unmatched cohort, patients from male clinics (n=784) were younger than males from general clinics (n=2726), median age: 31.2 vs 35.5 years. Those initiating at male clinics had higher median CD4 counts at ART initiation (Male Clinic 1: 329 [210–431], Male Clinic 2: 364 [IQR: 260–536] vs. general clinics 258 [IQR: 145–398] cells/mm3). The matched analysis included 1563 person-years among 1568 patients. Patients initiating ART at male clinics had lower attrition (HR: 0.83; 95% CI: 0.69–1.00). When matching and modelling was conducted for Male Clinic 1 and 2 separately, only the more established Male Clinic 1 showed a protective effect (HR 0.83; 95% CI: 0.65–1.07). The second study investigates whether attrition from care among youth (aged 12–25) on ART is lower among youth attending two youth clinics (Youth Clinic A and Youth Clinic B) compared to those attending general primary healthcare clinics. We also conducted a sub-analysis of patients attending adherence clubs (a model of ART delivery led by a lay facilitator, including a peer support group). We hypothesized that the effect of peer support in adherence clubs might be enhanced by the age-specific clubs at the youth clinics. It may also be further enhanced by additional elements of the adherence club model offered only in Youth Clinic A, including integration of family planning. Youth at the youth clinics were more likely than those at general clinics to have initiated ART before August 2011, particularly those at Youth Clinic B (23% compared to 11% at general clinics). The distribution of age, sex, and CD4 count at ART initiation was similar across youth and general clinics. We observed a protective effect of youth clinics against attrition: HR 0.81 (95% CI: 0.70–0.93) for Youth Clinic A and 0.85 (0.74–0.98) for Youth Clinic B, compared to youth at general clinics. Youth Clinic A club patients had lower attrition after joining an adherence club compared to general clinic patients in adherence clubs (crude HR: 0.56, 95% CI: 0.32–0.96; adjusted HR: 0.48, 95% CI: 0.28–0.85), while Youth Clinic B showed a smaller difference (crude HR: 0.83, 95% CI: 0.48–1.45; adjusted HR: 1.07, 95% CI: 0.60–1.90). The third study assesses attrition among patients in a pharmacy-led fast-track ART refill program compared to matched stable, otherwise healthy, patients who were eligible for the fast-track program at the same point in time and at the same facility but did not join. Matched pairs were followed from the date of the fast-track patient’s first fast-track ART pick-up, and attrition was compared using Cox proportional hazards regression. Fast-track patients and matched controls had similar characteristics at ART initiation and at fast-track enrolment. Fast-track patients were less likely to have previously experienced tuberculosis (23% vs 28%), diabetes (1% vs 7%) and hypertension (12% vs 27%), compared to those not in fast-track. Fast-track enrolment was highly protective against attrition (HR: 0.40; 95% CI: 0.31–0.51). We hypothesized that some of the association could be explained by confounding, arising from clinicians differentially referring patients to fast-track, possibly based on social, health, or mental health characteristics not reflected in the data. In a bias analysis using a plausible range of effects of such unmeasured confounding, the hazard ratio accounting for random and systematic error was 0.60 (95% interval: 0.42–0.89). All three studies show some protective effects of these differentiated models of service delivery against attrition. While stand-alone youth and male clinics are not feasible in all settings, and fast-track models may not be suited to all patients, these results suggest that multiple approaches tailored to specific populations’ needs can contribute to improving retention.

Enhanced Cooperation in the EU Abstract Enhanced cooperation has been a widely discussed in the context of the further possible development of the European integration and its direction. It represents a mechanism which introduces elements of flexible integration into the EU law. This thesis aims to provide a complete view of the process of enhanced cooperation. The first part focuses on the definition of flexibility and its theoretical concepts. The following parts of the thesis are then fully focused on enhanced cooperation as a specific legal instrument regulated by the Treaties. First of all, it mentions its historical development from the Treaty of Amsterdam to the Treaty of Lisbon and the changes it has undergone. After that there is the analysis of the legal provisions on enhanced cooperation itself. It discusses the whole process of establishing enhanced cooperation and the conditions necessary for that. There are also discussed special rules for activation of enhanced cooperation in the area of the common foreign and security policy and the police and judicial cooperation in criminal matters. Furthermore, a substantial part of the work is devoted to the application of enhanced cooperation in practice. Five cases of enhanced cooperation established so far are analysed in that part. In each case, the...

Only 4% of the teachers at a southeastern grade school met the differentiated instruction standard in the state's teacher evaluation system. A qualitative case study design was used to examine elementary (K-5) teachers' perceptions of individualized differentiated instruction as it relates to planning and preparation, and teaching and professional responsibilities at one school in a southeastern state. Individualized differentiated instruction is altering instruction to fit students' needs; teachers who lack individualized differentiated instruction skills do not meet students' specific instructional needs. Danielson's framework for teaching guided this study. The sample consisted of 12 regular education, reading or math teachers in grades K-5 at the study school. Data were collected through review of lesson plan documents and face-to-face interviews. Transcripts were coded and analyzed thematically, and comparative analysis was used to compare the themes to Danielson's conceptual framework. The findings suggested that teachers' use of individualized differentiated instruction was influenced by the amount of planning time, inadequate professional development, and a sense of professional responsibility regarding teaching using the Danielson framework. Participants' planning and preparation for individualized differentiation did not necessarily lead to teaching using differentiated instruction; therefore, a professional development project on the use of differentiated instruction with students was developed. The study impacts social change by providing recommendations for planning effective professional development that improves individualized differentiated instruction and student learning outcomes.

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The content in this study is about special educational guidance and how it contributes to inclusion through development of a differentiated instruction (DI). The study is based on previous research in three areas: inclusion, differentiated instruction and special education guidance. The concepts are defined and delimited based on national and international research. The research questions include difficulties faced by teachers in planning and the implementation of differentiated instruction in practice and how this work can be supported by special education guidance. The theoretical starting point is practice architectures (Kemmis et al., 2014). In the analysis even dilemma perspective (Nilholm, 2005; 2007) is used.  Action research is used as method and thematic analysis is used to analyse the empirical material. The thematic analysis shows that the teacher experienced pupils´ participation, and their different levels were challenging. The thematic analysis also showed that the special educator in the supervision used five strategies to support the teachers. The discussion includes dilemmas that are identified in the study from a techer perspective: the requirement for goal fulfillment versus pupils´need and conditions, percieved lack of time versus developing a differentiated a differentiated instruction and limitations in possibilities to organize teaching according to pupils´needs and conditions. In addition, special educational guidance and dilemmas are discussed and how supervison practice is affected by and shaped in an unequal school system.

This thesis presents a dynamic pricing model where a seller offers two types of a generic product to a random number of customers. Customers show up sequentially. When a customer arrives, he will ---depending on the prices---either purchase one unit of type 1 product or one unit of type 2 product, or will leave empty-handed. The sale ends either when the entire stock is sold out, or when the customers are exhausted. The seller's task is to post the optimal prices for the two product types to each customer to maximize the expected total revenue. We use dynamic programming to formulate this problem, and derive the optimal policy for special cases. For general cases, we develop an algorithm to approximate the optimal policy and use numerical examples to demonstrate the efficiency of the algorithm. Finally, we apply the results to a continuous-time model where customers arrive according to a Poisson process. We develop a heuristic policy and use numerical examples to show the heuristic policy is very effective. / Master of Science

Asymmetric digital subscriber line (ADSL) is a broadband access technology capable of delivering large bandwidth over existing copper telephone line infrastructure. This research aims at characterizing and analyzing TCP/IP performance in presence of a new protocol stack (TCP/IP over PPP and ATM) being promoted for one of the ADSL network architectures. Using extensive simulations, we verify the adverse effects of asymmetric links on the performance of TCP and additional throughput degradation caused by the overhead at the AAL5- ATM layers. This study involves unidirectional as well as bi-directional data transfer using different traffic mixes including bursty and non-bursty types of traffic. Bi-directional data transfer over asymmetric links results in ACK compression wherein TCP acknowledgements (ACKs) get bunched together behind larger data packets, further exacerbating the effect of asymmetry on TCP performance. By implementing the simulation model for PPP encapsulation over AAL5, we characterize its effect in terms of throughput degradation and excessive delay. We quantify the improvement in the throughput obtained by delaying the TCP ACKs and by TCP/IP header compression. These techniques being effective for unidirectional traffic over asymmetric links, however, do not prove as effective when ATM enters the scenario or in presence of bi-directional data transfer. Further, we implemented a simulation model of the Smart ACK Dropper (SAD), a technique to regulate the flow of TCP ACKs. Considerable improvement in performance especially in the presence of unidirectional data transfer is achieved using the SAD technique. Although the improvement is to a lesser extent in the presence of bi-directional data traffic, SAD helps the network in quickly recovering from the impact of ACK compression. We also propose and implement certain customized queuing/scheduling and policing mechanisms to enable differentiated servicing of TCP ACKs and data packets, and mitigate the effect of ACK compression. While providing considerable TCP performance improvement in presence of SAD, custom queuing also allows fair sharing of bandwidth between TCP flows, unlike priority queuing, which starves the low priority flow. The committed access rate (CAR)policing scheme provides considerable performance improvement when used with SAD, and is especially useful when TCP ACKs compete with bursty data traffic over the slower upstream. / Master of Science

English classrooms in Sweden host students of mixed abilities, all entitled to adapted education. Despite this, English language teaching, unlike other subjects, primarily relies on course books, serving as both learning tools and syllabus references. However, previous research has highlighted shortcomings in these books, such as insufficient vocabulary exercises and gaps in alignment with the syllabus. Although research and the Swedish National Agency of Education advocate for less reliance on course books and more communicative teaching, many teachers still find them useful. This study aims to explore the extent to which these course books allow for differentiation, to meet the needs of all students. The study employed triangulation method, by mixing a content analysis of 15 course books and interviews with six English teachers. The investigation's primary conclusions are that there are not many opportunities for differentiation within the books, but teachers seem to make do with alternative resources, adapting the books tasks and giving students varying degrees of support. While some differentiation is possible within course books, it may not fully address the needs of students of mixed-ability classrooms. Therefore, it could be concluded that the current approach may be insufficient to ensure that every student's needs are met, potentially limiting their language acquisition opportunities.

Esta pesquisa tem como objetivo analisar práticas de diferenciação pedagógica em escolas da rede municipal de educação de São Paulo. O conceito de diferenciação pedagógica emerge com a problemática do fracasso escolar, decorrente da universalização do ensino público. Neste trabalho, a partir da delimitação e discussão do conceito de diferenciação pedagógica, busca-se identificar a presença de ações diferenciadas de ensino em instituições da rede municipal de São Paulo, procurando-se responder às seguintes questões: qual é a característica das ações desenvolvidas e qual é o entendimento que os docentes têm acerca do conceito de diferenciação pedagógica? De que forma este entendimento se reflete nas práticas em sala de aula? Para responder a estas questões, procedeu-se à revisão de literatura sobre a temática da diferenciação pedagógica, bem como coletaram-se informações sobre a realidade empírica por meio da aplicação de 102 questionários, 4 entrevistas e observações in loco em 12 salas de aula de uma escola da Zona Leste de São Paulo. O estudo focalizou o trabalho dos professores do ciclo de alfabetização composto pelos 1ºs, 2ºs e 3ºs anos do Ensino Fundamental no componente de Língua Portuguesa. Os resultados obtidos mostraram que os docentes afirmam realizar práticas de diferenciação pedagógica com seus alunos; porém, os dados empíricos mostraram que as práticas, relatadas e observadas, não se coadunam com os princípios preconizados por autores que discutem a temática, como Perrenoud, Roldão, Tomlinsom, Pacheco entre outros. Além disso, observou-se que, ainda que documentos curriculares oficiais, produzidos nos âmbitos federal, estadual e municipal, remetam a princípios de diferenciação pedagógica, não são encontradas referências diretas a esse conceito. / This research aims to analyze practices of pedagogical differentiation in schools of the municipal education network of São Paulo. The concept of pedagogical differentiation emerges with the problem of school failure, resulting from the universalization of public education. In this work, from the delimitation and discussion of the concept of pedagogical differentiation, we seek to identify the presence of differentiated teaching actions in institutions of the municipal network of São Paulo, seeking to answer the following questions: what is the characteristic of the actions developed and what is the understanding that teachers have about the concept of pedagogical differentiation? How is this understanding reflected in classroom practices? In order to answer these questions, a literature review on the subject of pedagogical differentiation was carried out, as well as information on the empirical reality through the application of 102 questionnaires, 4 interviews and on-site observations in 12 classrooms of one school in the East Zone of São Paulo. The study focused on the work of the teachers of the literacy cycle - composed of the 1st, 2nd and 3rd years of elementary education - in the Portuguese Language component. The results showed that the teachers affirm the practice of pedagogical differentiation with their students; however, the empirical data showed that the practices, reported and observed, are not in line with the principles advocated by authors who discuss the subject, such as Perrenoud, Roldão, Tomlinsom, Pacheco and others. In addition, it was observed that, although official curricular documents produced at the federal, state and municipal levels refer to principles of pedagogical differentiation, no direct references to this concept are found.