A Qualitative Study of Contextual Factors’ Impact on the Adaptation of a Caregiver-mediated Early Autism Intervention in South Africa

Background: Autism Spectrum Disorder (ASD) is a major global health challenge as the majority of individuals with ASD live in low- and middle-income countries (LMICs) and receive little to no services or support from health or social care systems. Despite this global crisis, the development and validation of ASD interventions has almost exclusively occurred in high-income countries, leaving many unanswered questions regarding what contextual factors would need to be considered to ensure the effectiveness of interventions in LMICs. This study sought to conduct explorative research on the contextual adaptation of a caregiver-mediated early ASD intervention for use in a low-resource setting in South Africa.

Methods: Participants included 22 caregivers of children with autism, including mothers (n=16), fathers (n=4), and grandmothers (n=2). Four focus groups discussions were conducted in Cape Town, South Africa with caregivers and lasted between 1.5-3.5 hours in length. Data was recorded, translated, and transcribed by research personnel. Data was then coded for emerging themes and analyzed using the NVivo qualitative data analysis software package.

Results: Nine contextual factors were reported to be important for the adaptation process including culture, language, location of treatment, cost of treatment, type of service provider, familial needs, length of treatment, support, and parenting practices. One contextual factor, evidence-based treatment, was reported to be both important and not important for adaptation by caregivers. The contextual factor of stigma was identified as an emerging theme and a specifically relevant challenge when developing an ASD intervention for use in a South African context.

Conclusions: Eleven contextual factors were discussed in detail by caregivers and examples were given regarding the challenges, sources, and preferences related to the contextual adaptation of a parent-mediated early ASD intervention in South Africa. Caregivers reported a preference for an affordable, in-home, individualized early ASD intervention, where they have an active voice in shaping treatment goals. Distrust of community-based nurses and health workers to deliver an early ASD intervention and challenges associated with ASD-based stigma were two unanticipated findings from this data set. Implications for practice and further research are discussed.

From traditional resource to global commodities: a comparison of Rhodiola species using NMR spectroscopy - metabolomics and HPTLC

The fast developing international trade of products based on traditional knowledge and their value chains has become an important aspect of the ethnopharmacological debate. The structure and diversity of value chains and their impact on the phytochemical composition of herbal medicinal products has been overlooked in the debate about quality problems in transnational trade. Different government policies and regulations governing trade in herbal medicinal products impact on such value chains. Medicinal Rhodiola species, including Rhodiola rosea L. and Rhodiola crenulata (Hook.f. & Thomson) H.Ohba, have been used widely in Europe and Asia as traditional herbal medicines with numerous claims for their therapeutic effects. Faced with resource depletion and environment destruction, R. rosea and R. crenulata are becoming endangered, making them more economically valuable to collectors and middlemen, and also increasing the risk of adulteration and low quality. We compare the phytochemical differences among Rhodiola raw materials available on the market to provide a practical method for Rhodiola authentication and the detection of potential adulterant compounds. Samples were collected from Europe and Asia and nuclear magnetic resonance spectroscopy coupled with multivariate analysis software and high performance thin layer chromatography techniques were used to analyse the samples. A method was developed to quantify the amount of adulterant species contained within mixtures. We compared the phytochemical composition of collected Rhodiola samples to authenticated samples. Rosavin and rosarin were mainly present in R. rosea whereas crenulatin was only present in R. crenulata. 30% of the Rhodiola samples purchased from the Chinese market were adulterated by other Rhodiola spp. Moreover, 7 % of the raw-material samples were not labelled satifactorily. The utilisation of both 1H-NMR and HPTLC methods provided an integrated analysis of the phytochemical differences and novel identification method for R. rosea and R. crenulata. Using 1H-NMR spectroscopy it was possible to quantify the presence of R. crenulata in admixtures with R. rosea. This quantitative technique could be used in the future to assess a variety of herbal drugs and products. This project also highlights the need to further study the links between producers and consumers in national and trans-national trade.

An investigation into the role of interleukin-6 in linking systemic and local inflammatory responses in patients with colorectal cancer

Colorectal cancer is the second most common cause of cancer death in the UK. It is accepted that both tumour and host factors are important determinants of disease progression and survival. While systemic and local inflammatory responses are increasingly recognized to be of particular importance the understanding of the mechanisms linking these important inflammatory processes remains unclear. This thesis examines the prognostic importance of measures of systemic and local inflammation and proposes a hypothesis for a link between tumour necrosis, systemic and local inflammatory responses in patients with colorectal cancer. Chapter 3 reports the comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer. In Chapter 3 the results demonstrate that there was no significant overall change in either mGPS or NLR from pre- to post- operatively. This study highlighted the associations between pre- and post- operative mGPS and NLR and T-stage (p<0.001), TNM stage (p<0.005) and cancer-specific survival. The relationships between pre-operative measurements were examined using multivariate analysis. For pre-operative measurement both mGPS and NLR were associated with cancer-specific survival while when post-operative measures were examined only mGPS was specifically associated with cancer-specific survival (HR 4.81, CI 2.13-10.83, P<0.001). Chapter 4 examines the prognostic value of the Klintrup-Makinen scoring method and the existing limitations with regard to its clinical utility. An automated scoring method using commercially available image analysis software was developed and compared with manual scoring of tumour inflammatory infiltrates. This study demonstrated that both manual K-M scoring (p<0.001) and automated K-M scoring (p<0.05) had prognostic value in patients who had undergone potentially curative resection of colorectal cancer, and that the novel automated method may provide an objective method of assessment of tumour inflammatory infiltrates using routinely stained haematoxylin and eosin sections of tumour samples. In chapter 5 a hypothesis was proposed that Interleukin-6 may link tumour necrosis and systemic and local inflammatory responses in patients with colorectal cancer. This chapter examined the basis for this hypothesis, which is presented in figure 5.1. In addition, in chapter 5 the importance of this potential link is examined. In chapter 6, the hypothesis outlined in chapter 5 was examined in a cohort of patients who had undergone attempted curative resection of colorectal cancer. This study examined the inter-relationships between circulating mediators, in particular IL-6, tumour necrosis and systemic and local inflammatory responses. This results of this study demonstrated that IL-6 was associated with tumour necrosis (<0.001) and mGPS (<0.001) independent of T-stage. Thus adding weight to the hypothesis that elevated circulating concentrations of IL-6 may play a role in modulating both the systemic and local inflammatory responses in patients with cancer. Chapter 7 further develops the hypothesis that IL-6 signalling may be important in modulating systemic and local inflammatory responses in patients with colorectal cancer. Further, in chapter 7 the basis for the role of trans-signalling in this signaling pathway was examined. In this study, we reported that neither expression of the soluble IL-6 receptor or soluble gp130 were associated with systemic or local inflammatory responses. As a result the possible reasons for these findings were explored and future work suggested. A prospective database of patients undergoing attempted curative resection of colorectal cancer in Glasgow Royal Infirmary was used throughout this thesis. This database was created and is maintained regularly by successive research fellows at the Royal Infirmary. The work presented in this thesis highlights the importance of the host response in the form of systemic and local inflammation in patients with colorectal cancer and proposes a link between these responses and tumour necrosis. In addition, this work adds weight to the body of evidence suggesting that assessment of these host responses may improve stratification to treatment for patients with colorectal cancer. Further, this work proposes a mechanistic link, between tumour necrosis, systemic and local inflammatory responses through Interleukin-6, that merits further investigation.

Report of the Workshop on Growth-increment Chronologies in Marine Fish: climate-ecosystem interactions in the North Atlantic 2 (WKGIC2). 18-22 April 2016 Esporles, Mallorca, Spain

Over the past several decades, thousands of otoliths, bivalve shells, and scales have been collected for the purposes of age determination and remain archived in European and North American fisheries laboratories. Advances in digital imaging and computer software combined with techniques developed by tree-ring scientists provide a means by which to extract additional levels of information in these calcified structures and generate annually resolved (one value per year), multidecadal time-series of population-level growth anomalies. Chemical and isotopic properties may also be extracted to provide additional information regarding the environmental conditions these organisms experienced.Given that they are exactly placed in time, chronologies can be directly compared to instrumental climate records, chronologies from other regions or species, or time-seriesof other biological phenomena. In this way, chronologies may be used to reconstruct historical ranges of environmental variability, identify climatic drivers of growth, establish linkages within and among species, and generate ecosystem-level indicators. Following the first workshop in Hamburg, Germany, in December 2014, the second workshop on Growth increment Chronologies in Marine Fish: climate-ecosystem interactions in the North Atlantic (WKGIC2) met at the Mediterranean Institute for Advanced Studies headquarters in Esporles, Spain, on 18–22 April 2016, chaired by Bryan Black (USA) and Christoph Stransky (Germany).Thirty-six participants from fifteen different countries attended. Objectives were to i) review the applications of chronologies developed from growth-increment widths in the hard parts (otoliths, shells, scales) of marine fish and bivalve species ii) review the fundamentals of crossdating and chronology development, iii) discuss assumptions and limitations of these approaches, iv) measure otolith growth-increment widths in image analysis software, v) learn software to statistically check increment dating accuracy, vi) generate a growth increment chronology and relate it to climate indices, and vii) initiate cooperative projects or training exercises to commence after the workshop.The workshop began with an overview of tree-ring techniques of chronology development, including a hands-on exercise in cross dating. Next, we discussed the applications of fish and bivalve biochronologies and the range of issues that could be addressed. We then reviewed key assumptions and limitations, especially those associated with short-lived species for which there are numerous and extensive otolith archives in European fisheries labs. Next, participants were provided with images of European plaice otoliths from the North Sea and taught to measure increment widths in image analysis software. Upon completion of measurements, techniques of chronology development were discussed and contrasted to those that have been applied for long-lived species. Plaice growth time-series were then related to environmental variability using the KNMI Climate Explorer. Finally, potential future collaborations and funding opportunities were discussed, and there was a clear desire to meet again to compare various statistical techniques for chronology development using a range existing fish, bivalve, and tree growth-increment datasets. Overall, we hope to increase the use of these techniques, and over the long term, develop networks of biochronologies for integrative analyses of ecosystem functioning and relationships to long-term climate variability and fishing pressure.

Propuesta de un modelo de evaluación bidimensional en Moodle

El modelo de evaluación bidimensional MEB en la educación superior, propuesto en este trabajo mide el conocimiento de estudiantes versus grado de certeza. El análisis de estas dos dimensiones permite al profesor determinar áreas de conocimiento a profundizar con sus estudiantes. La investigación fue descriptiva y correlacional, fueron aplicados métodos científico e inductivo. Las técnicas utilizadas fueron cuestionarios y análisis estadístico y recursos técnicos fueron: sistema de gestión de aprendizaje Moodle, software para análisis matemático MATLAB, EXCEL, laboratorios de la Facultad de Informática y Electrónica (FIE) de la Escuela Superior Politécnica de Chimborazo (ESPOCH), institución donde se llevó a cabo el estudio. El MEB propone la aplicación de cuestionarios de selección múltiple con el mecanismo CBM (Certainty based marking - Marcado basado en la certeza), sobre un aula virtual creada en el sistema Moodle. CBM permite medir por cada pregunta de un cuestionario las dimensiones conocimiento y certeza.

Sports sponsorship as a channel for brand engagement on social media

The purpose of this Mater’s Thesis was to examine how sports sponsorship can be used as a channel for brand engagement on social media. All these three concepts have been researched previously, however, up until now they have been studied separately. Therefore, the aim was also to investigate the interrelations between these three concepts, as there is a lack of academic base on the matter. The theory of the research was based on existing academic researches of social media, brand engagement and sports sponsorship. The empirical part of the research was conducted by utilizing quantitative research method. An online questionnaire was published on Facebook pages of two Liiga ice hockey teams. In the end the total sample consisted of 322 viable respondents. The collected data was analyzed by using statistical analysis software, SPSS. The findings of the empirical research reveal that information, enjoyment, personal identity, social interaction and compensation motivate consumers to engage with brands on social media. However, the behavior of consumers is more passive than active brand engagement. Personal identity and compensation serve as motivational reasons for brand engagement on both active and passive level, while the rest are only passive brand engagement. Besides motivation there are other variables that affect consumers. Support for the team reflects to brand engagement, which is passive brand engagement. The visibility of the brand during the event is linked to both active and passive brand engagement. Prior information of sports team and event and frequency of attendance can be linked only to active brand engagement. On the other hand, congruence between the team and brand reflects only to passive brand engagement.

Effects of a resistance and stretching training program on forward head and protracted shoulder posture in physical education classes in students aged 15-17 years old

Purpose: This study aimed to characterize the postural alignment of the head and shoulder in the sagittal plane of Portuguese adolescents, 15-17 years old, and to evaluate the effects of a 32-week resistance and stretching training program applied in Physical Education classes on forward head posture and protracted shoulder posture of Portuguese adolescents. After 32-training weeks the detraining effects after a 16-week period were measured. Methods: This randomized and controlled study was conducted in two secondary schools in Portugal for 48 weeks. Prior the study 275 students aged 15-17 years old were evaluated. Sagittal head, cervical and shoulder angle were measured with photogrammetry and Postural Analysis Software. After this assessment 130 adolescents were considered to have forward head and protracted shoulder posture and were randomly assigned to a control group, an experimental group one or experimental group two. The control group (n=46) only did the Physical Education classes whereas the intervention group one (n=42) and two (n=42) performed a 16-week and 32-week stretching and strengthening program in addition to Physical Education classes, respectively. The postural angles were measured before and after the 16-week and 32-week time intervention period for the three groups and after a 16-week detraining period following the 32-week in intervention group two. Results: 68% of the adolescents studied revealed anteriorization of the head whereas 58% of them had protraction of the shoulder. Significant increases were observed in the cervical and shoulder angle in the experimental group (n=84) following the 16-week and in experimental group two (n=42)after the 32 week-intervention period. After the 16-week detraining period no significant differences were observed in the three postural angles in the intervention group two. Conclusions: Forward head and protracted shoulder are common postural disorders in Portuguese adolescents. The exercise intervention was successful ate decreasing forward head and protracted shoulder in adolescents. Detraining period of 16-week didn´t reduce the overall training effects.

Bem-estar subjectivo: processos cognitivos e afecto positivo

O presente trabalho de investigação visa aprofundar o campo de estudo no âmbito do Bem-Estar subjetivo. Especificamente, propõe-se apreciar qual o papel do Processamento Cognitivo "Aberto" (e outras formas de Coping) na relação entre Satisfação com o Suporte Social e o Afecto Positivo e Negativo. A metodologia usada segue um método correlaciona/ quantitativo através do recurso ao software de análise estatística SPSS. As análises de regressão simples e múltipla mostraram que diferentes variáveis, como as cognitivas (Processamento Cognitivo "Aberto" e outras formas de Coping) e os pessoais e sócio-demográficas (Género e Grau de Escolaridade), se encontram associados aos níveis de Afecto, quer Positivo quer Negativo, e contribuem também de formas distintas para explicar a sua variabilidade. Para além disso, as mesmas relações parecem ser influenciadas pelos níveis de Saúde Mental dos participantes. Os resultados do presente estudo sugerem importantes implicações teóricas e práticas no âmbito da Saúde Mental. /ABSTRACT: This research work aims to deepen the field of study within the framework of Subjective Well-Being. Specifically, it proposes to assess the role of the Broad-Minded Coping (and other forms of Coping) in the relationship between Satisfaction with the Social Support and the Positive and Negative Affect. The methodology used follows a correlative quantitative method through the use of the statistical analysis software SPSS. Multiple and simple regression analyses showed that different variables, such as cognitive (Broad-Minded Coping and other forms of Coping) and personal and socio-demographic data (Gender and Scholarization), are associated with the levels of Affect, either Positive or Negative, and they also contribute differently to explain its variability. ln addition, these relationships seem to be influenced by the participants' Mental Health levels. The results of this study suggest important theoretical and practical implications in the context of Mental Health.

Evaluación de los cambios dentarios y su influencia en los tejidos blandos de pacientes tratados con sistema Damon Q y MBT

Se realizó una investigación con el objetivo de establecer los cambios dentarios y evaluar la influencia de estos en los tejidos blandos comparando pacientes tratados con sistema Damon Q (N=23) y MBT (N=16). Se seleccionó una muestra de estudio conformada por 39 individuos siendo 28 mujeres y 11 varones de edades comprendidas entre 11 y 26 años. Se registraron radiografías cefálicas laterales digitales tomadas antes y después de concluido el tratamiento. Las inclinaciones de los incisivos superiores e inferiores así como las alteraciones del perfil facial fueron medidas mediante el Software de análisis cefalométrico Nemotec Dental. Para determinar los cambios en los tejidos duros y blandos se aplicó la prueba T-Student verificándose diferencias estadísticamente significativas (p < 0,05) para los dos sistemas en las variables: ángulo incisivo maxilar, mandibular, posición del labio inferior según el plano estético de Ricketts y el de Burstone. La correlación existente entre los cambios en la inclinación de los incisivos y la posición labial, se evaluó mediante el coeficiente de relación de Pearson encontrando para el sistema Damon una correlación entre la posición del incisivo superior y la del labio superior e inferior, la posición del incisivo inferior tuvo una correlación moderada con el labio inferior, con la técnica MBT se encontró una relación moderada entre la posición del incisivo superior y el labio inferior. Se concluyó que existen cambios postratamiento en la posición de los incisivos, así como protrusión labial inferior hallando relación entre la inclinación vestibular de los incisivos y el movimiento de los labios en ambas técnicas

Development of Safety Performance Functions for SafetyAnalyst Applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency’s safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.

Examination of the Effect of Time Delay on Fragmentation

The main objective of blasting is to produce optimum fragmentation for downstream processing. Fragmentation is usually considered optimum when the average fragment size is minimum and the fragmentation distribution as uniform as possible. One of the parameters affecting blasting fragmentation is believed to be time delay between holes of the same row. Although one can find a significant number of studies in the literature, which examine the relationship between time delay and fragmentation, their results have been often controversial. The purpose of this work is to increase the level of understanding of how time delay between holes of the same row affects fragmentation. Two series of experiments were conducted for this purpose. The first series involved tests on small scale grout and granite blocks to determine the moment of burden detachment. The instrumentation used for these experiments consisted mainly of strain gauges and piezoelectric sensors. Some experiments were also recorded with a high speed camera. It was concluded that the time of detachment for this specific setup is between 300 and 600 μs. The second series of experiments involved blasting of a 2 meter high granite bench and its purpose was the determination of the hole-to-hole delay that provides optimum fragmentation. The fragmentation results were assessed with image analysis software. Moreover, vibration was measured close to the blast and the experiments were recorded with high speed cameras. The results suggest that fragmentation was optimum when delays between 4 and 6 ms were used for this specific setup. Also, it was found that the moment at which gases first appear to be venting from the face was consistently around 6 ms after detonation.

MicroRNA modulation of aldosterone production in the adrenal gland

Hypertension is the major risk factor for coronary disease worldwide. Primary hypertension is idiopathic in origin but is thought to arise from multiple risk factors including genetic, lifestyle and environmental influences. Secondary hypertension has a more definite aetiology; its major single cause is primary aldosteronism (PA), the greatest proportion of which is caused by aldosteroneproducing adenoma (APA), where aldosterone is synthesized at high levels by an adenoma of the adrenal gland. There is strong evidence to show that high aldosterone levels cause adverse effects on cardiovascular, cerebrovascular, renal and other systems. Extensive studies have been conducted to analyse the role that regulation of CYP11B2, the gene encoding the aldosterone synthase enzyme plays in determining aldosterone production and the development of hypertension. One significant regulatory factor that has only recently emerged is microRNA (miRNA). miRNAs are small non-coding RNAs, synthesized by a series of enzymatic processes, that negatively regulate gene expression at the posttranscriptional level. Detection and manipulation of miRNA is now known to be a viable method in the treatment, prevention and prognosis of certain diseases. The aim of the present study was to identify miRNAs likely to have a role in the regulation of corticosteroid biosynthesis. To achieve this, the miRNA profile of APA and normal human adrenal tissue was compared, as was the H295R adrenocortical cell line model of adrenocortical function, under both basal conditions and following stimulation of aldosterone production. Key differentially-expressed miRNAs were then identified and bioinformatic tools used to identify likely mRNA targets and pathways for these miRNAs, several of which were investigated and validated using in vitro methods. The background to this study is set out in Chapter 1 of this thesis, followed by a description of the major technical methods employed in Chapter 2. Chapter 3 presents the first of the study results, analysing differences in miRNA profile between APA and normal human adrenal tissue. Microarray was implemented to detect the expression of miRNAs in these two tissue types and several miRNAs were found to vary significantly and consistently between them. Furthermore, members of several miRNA clusters exhibited similar changes in expression pattern between the two tissues e.g. members of cluster miR-29b-1 (miR-29a-3p and miR-29b-3p) and of cluster miR-29b-2 (miR-29b-3p and miR-29c- 3p) are downregulated in APA, while members of cluster let-7a-1 (let-7a-5p and let-7d-5p), cluster let-7a-3 (let-7a-5p and let-7b-5p) and cluster miR-134 (miR- 134 and miR-382) are upregulated. Further bioinformatic analysis explored the possible biological function of these miRNAs using Ingenuity® Systems Pathway Analysis software. This led to the identification of validated mRNAs already known to be targeted by these miRNAs, as well as the prediction of other mRNAs that are likely targets and which are involved in processes relevant to APA pathology including cholesterol synthesis (HMGCR) and corticosteroidogenesis (CYP11B2). It was therefore hypothesised that increases in miR-125a-5p or miR- 335-5p would reduce HMGCR and CYP11B2 expression. Chapter 4 describes the characterisation of H295R cells of different strains and sources (H295R Strain 1, 2, 3 and HAC 15). Expression of CYP11B2 was assessed following application of 3 different stimulants: Angio II, dbcAMP and KCl. The most responsive strain to stimulation was Strain 1 at lower passage numbers. Furthermore, H295R proliferation increased following Angio II stimulation. In Chapter 5, the hypothesis that increases in miR-125a-5p or miR-335-5p reduces HMGCR and CYP11B2 expression was tested using realtime quantitative RT-PCR and transfection of miRNA mimics and inhibitors into the H295R cell line model of adrenocortical function. In this way, miR-125a-5p and miR-335-5p were shown to downregulate CYP11B2 and HMGCR expression, thereby validating certain of the bioinformatic predictions generated in Chapter 3. The study of miRNA profile in the H295R cell lines was conducted in Chapter 6, analysing how it changes under conditions that increase aldosterone secretion, including stimulation Angiotensin II, potassium chloride or dibutyryl cAMP (as a substitute for adrenocorticotropic hormone). miRNA profiling identified 7 miRNAs that are consistently downregulated by all three stimuli relative to basal cells: miR-106a-5p, miR-154-3p, miR-17-5p, miR-196b-5p, miR-19a-3p, miR-20b- 5p and miR-766-3p. These miRNAs include those derived from cluster miR-106a- 5p/miR-20b-5p and cluster miR-17-5p/miR-19a-3p, each producing a single polycistronic transcript. IPA bioinformatic analysis was again applied to identify experimentally validated and predicted mRNA targets of these miRNAs and the key biological pathways likely to be affected. This predicted several interactions between miRNAs derived from cluster miR-17-5p/miR-19a-3p and important mRNAs involved in cholesterol biosynthesis: LDLR and ABCA1. These predictions were investigated by in vitro experiment. miR-17-5p/miR-106a-p and miR-20b-5p were found to be consistently downregulated by stimulation of aldosterone biosynthesis. Moreover, miR-766-3p was upregulation throughout. Furthermore, I was able to validate the downregulation of LDLR by miR-17 transfection, as predicted by IPA. In summary, this study identified key miRNAs that are differentially-expressed in vivo in cases of APA or in vitro following stimulation of aldosterone biosynthesis. The many possible biological actions these miRNAs could have were filtered by bioinformatic analysis and selected interactions validated in vitro. While direct actions of these miRNAs on steroidogenic enzymes were identified, cholesterol handling also emerged as an important target and may represent a useful point of intervention in future therapies designed to modulate aldosterone biosynthesis and reduce its harmful effects.

A motivação dos docentes no ensino superior face ao processo de Bolonha: um estudo de caso

Este trabalho pretende estudar a motivação dos docentes da licenciatura de radioterapia da Escola Superior de Tecnologias da Saúde de Lisboa, face ao processo de Bolonha. Realizou-se um enquadramento teórico dos conceitos base, como motivação e processo de Bolonha. O estudo foi definido como um estudo de caso, com uma amostra de 3 elementos. Aplicou-se três entrevistas a cada um dos entrevistados, denominadas por entrevista, entrevista reflexiva e entrevista reflexiva aprofundada. Para a análise dos dados utilizou-se um software de análise de conteúdo -AQUAD 6.0. Os resultados são apresentados em forma de tabelas e segmentos de texto extraídos do software. Na discussão dos resultados verifica-se que de uma forma geral os resultados vão ao encontro da literatura existente e nas considerações finais respondem-se às questões de investigação inicialmente realizadas, mas também são apresentadas as limitações ao estudo, bem como futuras investigações. ABSTRACT: lt is intended with this work to study the motivation of the radiotherapy graduated professors of the Higher School of Health Technology of Lisbon, regarding the Bologna process. lt was performed a theoretical frame of reference of the basic concepts such as motivation and the Bologna Process. The study was defined as a case study, with a sample of three elements. Three interviews were performed to each interviewed person, defined as interview, reflexive interview and deepened reflexive interview. For the data analysis it was used a content analysis software - AQUAD 6.0. The results are presented in table form and with text sectors obtained from the software. ln the discussion of the results one comes to the conclusion that, in general, they match the available literary writings and in the final reflexions it is answered to the investigation questions initially asked but also presented the study limitations as well as future investigations.

Global Fatigue Assessment of a Decommissioned Jacket Platform for a Sustainable Reuse as an Offshore Wind Turbine

When the offshore oil and gas supplies exhaust, offshore platforms must be decommissioned and removed. The present thesis highlights the importance of evaluating the possibility of reuse of decommissioned offshore jacket platforms for offshore wind energy. In order to shift to the new structure, the topside must be removed from the substructure and a wind turbine can be installed in its place. The feasibility of this project was investigated using a finite element analysis software called Sesam. To study fatigue life in offshore structures, an exhaustive review of the background and state of the art was done. A finite element model was created by the means of Sesam and two different fatigue analysis approaches were applied and compared. In the end, an analysis methodology is suggested for the structural fatigue analysis of offshore wind turbine structures based on international standards, addressing the industry’s need to account for the combined effect of wind and hydrodynamic loads in these type of structures.