The objective of this thesis research is to optimize network throughput and fairness, and enhance bandwidth utilization in wireless mobile multi-hop relay (MMR) networks. To enhance bandwidth utilization, we propose an adaptive OFDMA frame structure which is used by the base station and the non-transparent relay stations. To optimize throughput and fairness, we develop an adaptive OFDMA allocation algorithm by using the proposed adaptive OFDMA frame. The effectiveness of the proposed schemes has been verified by numeric simulations. Providing ubiquitous coverage with wireless metropolitan area networks (WMANs) can be costly, especially in sparsely populated areas. In this scenario, cheaper relay stations (RSs) can be used to provide coverage instead of expensive base stations (BSs). The RS extends the coverage area of traditional BSs. This sort of network is known as a wireless MMR network. This thesis focuses on MMR networks that use orthogonal frequency division multiple access (OFDMA) and time division duplex (TDD) as a multiple access scheme and a duplex communication technique (e.g., WiMAX). The use of OFDMA resources (e.g., OFDMA symbols and subcarriers) and how they are shared in current schemes can reduce system capacity and network throughput in certain scenarios. To increase the capacity of the MMR network, we propose a new protocol that uses an adaptive OFDMA frame structure for BSs and RSs. We also propose adaptive OFDMA resource allocation for subscriber stations (SSs) within a BS or RS. We derive the maximum OFDMA resources that RSs can be assigned and synchronize access zones and relay zones between a superior station and its subordinate RSs. This is bounded by three properties defined in this thesis: a data relay property, a maximum balance property, and a relay zone limitation property. Finally, we propose max-min and proportional fairness schemes that use the proposed adaptive frame structure. The proposed scheme is the first approach that incorporates the adaptive technique for wireless MMR networks. We evaluate our scheme using simulations and numerical analysis. Results show that our technique improves resource allocation in wireless MMR networks. Further, in asymmetric distributions of SSs between access zones and relay zones, the proposed OFDMA allocation scheme performs two times better than the non-adaptive allocation scheme in terms of average max-min fairness and 70% better in terms of average throughput.

Bakgrund: Vaccinationstäckning är ett av de viktigaste och mest kostnadseffektiva sättet att förbättra den globala folkhälsan. Trots det uppfattas vacciner som osäkert och onödigt av allt fler individer. Försämrad vaccinationstäckning påverkar flockimmuniteten med ökad risk för nya sjukdomsutbrott och epidemier. Syfte: Syftet var att undersöka och sammanställa den vetenskapliga litteraturen om vilka faktorer som påverkar vårdnadshavarnas beslut att vaccinera eller inte vaccinera sina barn mot mässling-påssjuka-röda hund (MPR). Metod: Systematisk litteraturöversikt där totalt tio vetenskapliga artiklar ligger till grund för resultatet. The Health Belief Model har använts som teoretisk utgångspunkt. Resultat: Flera faktorer var viktiga för föräldrars beslut om vaccination. Fem faktorer identifierades som påverkar föräldrar att inte vaccinera sina barn: att föredra naturlig immunisering, rädsla för biverkningar, rädsla för vaccinet, misstro till myndigheter och förebygga sjukdom genom livsstil. Fyra faktorer som påverkar föräldrar att låta vaccinera sina barn identifierades: att undvika sjukdom, värna om flockimmunitet, fördelar överväger nackdelar samt kunskap och information om sjukdomarna och vaccinet. I resultatet identifierades också ett bifynd, att låta barnets immunsystem mogna innan vaccination. Både föräldrar som vaccinerade och inte vaccinerade sina barn tyckte att det fanns för lite information om vaccinet och dess biverkningar. Slutsats: Flera faktorer påverkar föräldrars beslut om vaccination för sina barn mot MPR. Både föräldrar som vaccinerar och inte vaccinerar sina barn tycker informationen om vaccin och dess biverkningar är för knapphändig och svårtillgänglig. Det är viktigt som sjuksköterska att ha kunskap om vilka faktorer som påverkar föräldrars beslut för att kunna bemöta föräldrars oro och bistå med adekvat och evidensbaserad information. / Background: Vaccination coverage is one of the most important and cost-effective ways to improve global health. Despite this more and more people feel uncertain about vaccinations. Impaired vaccination coverage affects the herd immunity and leads to an increased risk of disease outbreaks and epidemics. Aim: The aim of this study was to examine which factors influence parents’ decisions regarding vaccination of their children against measles-mumps-rubella (MMR). Method: A systematic review where the result is based on ten scientific articles. The Health Belief Model was used as theoretical framework. Results: Several factors were important for the decision to vaccinate or not. Five factors were identified among parents not vaccinating: to prefer natural immunization, fear of side effects, fear of the vaccine, mistrust in the authorities and prevent disease through lifestyle. While four factors were identified among parents vaccinating: to prevent disease, to protect the herd immunity, the advantages outweigh disadvantages, and knowledge and information about the disease and the vaccine. In addition, the finding, to let the child's immune system mature before vaccination was identified. Both parents who accept vaccination and parents who decline vaccination of their children considered the information about the vaccine inadequate. Conclusion: Several factors influence parents’ decision regarding vaccination of their children against MMR. Both parents who accept vaccination and parents who decline vaccination of their children consider the information about the vaccine and its side effects too scant and difficult to access. It's important that nurses have knowledge about factors that influence parents' decisions in order to respond to their concerns and provide appropriate and evidence-based information.

Hereditary non-polyposis colon cancer syndrome (HNPCC) is associated with an increased risk of developing several types of cancer and is the most common cause of hereditary ovarian cancer after BRCA1 and BRCA2 mutations. HNPCC results from a germline mutation in one of the DNA mismatch repair (MMR) genes: MLH1, MSH2, PMS1, PMS2, MSH6, MSH3 and MLH3. While there has been extensive investigation of MMR deficiency in colorectal cancer, MMR in ovarian cancer is relatively under-investigated. The goal of this project was to study MMR deficiency in ovarian cancer at both the clinical and molecular level. The first aim was to examine the frequency of MMR loss in a large patient cohort and investigate the clinical consequences of MMR deficiency. The second aim was to describe the molecular characteristics of MMR deficiency in ovarian cancer cell lines and establish an in vitro cell line model of MMR deficiency in ovarian cancer. The third aim was to identify synthetic lethal strategies for the treatment of ovarian cancer to maximise cytotoxicity in a MMR-deficient background. In order to characterise the clinical consequences of MMR deficiency, a large patient cohort was studied with regard to MMR status. Three tissue microarrays consisting of 581 ovarian tumours were constructed, and expression of the four most frequently lost MMR proteins: MLH1, MSH2, PMS2 and MSH6 were detected by immunohistochemistry. Afterwards, MMR status and histology subtypes were analysed in combination with the associated clinical data. The overall incidence of MMR deficiency (loss of any MMR protein) was 15.7%, with PMS2 being the most frequently lost protein (9.7%). In addition, MMR deficiency tended to appear in a grouped fashion: MLH1 with PMS2; MSH2 with MSH6. Patients with non-serous subtypes of ovarian cancer, clear cell or mucinous especially, had higher incidence of MMR deficiency compared to patients with serous ovarian cancer. Overall MMR deficient patients were more likely to be diagnosed at early stages compared with MMR proficient patients, and this is probably due to the association between MMR deficiency and non-serous histology. However, platinum-based treatment for patients with MMR deficiency gives no advantage over those without MMR deficiency. Therefore better treatments for this subgroup of patients may be needed. The features of MMR deficiency in ovarian cancer were also characterized at the molecular level. After quantifying mRNA and protein expression of MMR genes in 19 ovarian cell lines, three cell lines (SKOV3, TOV21G and IGROV1) were found to have a defect in MLH1 expression at both the mRNA and protein level. Interestingly, the three cell lines also carried a defect in PMS2 expression at the protein level but not at the mRNA level, which is consistent with our clinical data demonstrating that MLH1 protein and PMS2 protein are paired in loss. In addition, across the 19 cell lines, MLH1 and PMS2 showed positive correlation at both the mRNA level (R=0.53, p=0.02) and protein level (R=0.72, p=0.0006). In order to study co-expression of MLH1 and PMS2, a plasmid encoding the cDNA for MLH1 was transfected into the three MLH1 deficient cell lines; and conversely siRNA targeting MLH1 was transfected into the MMR proficient cell line A2780 and expression of MLH1 protein and PMS2 protein was quantified. The results showed that re-introduction of MLH1 into MLH1 deficient cells resulted in increased expression of PMS2 protein, while knocking down MLH1 in MMR proficient cells leads to decreased PMS2 protein expression. This indicates that MLH1 may play a crucial role in regulating PMS2 protein expression. As the three MLH1 and PMS2 protein deficient cell lines all express PMS2 mRNA, the regulation of PMS2 expression by MLH1 is likely to be at the translational or post-translational level. However, the expression of PMS2 protein was not increased in the absence of MLH1, even when the proteasomal and lysosomal protein degradation pathways were blocked (as seen with SKOV3 cells), suggesting decreased PMS2 protein expression is not due to rapid degradation in the absence of MLH1. Therefore MLH1 may play a role in regulating the synthesis of PMS2 protein at the translational level, rather than preventing the degradation of PMS2. Thus, to investigate the mechanism by which PMS2 protein levels are regulated by MLH1, future work should focus on translational regulation of PMS2. In order to identify synthetic lethal strategies to target MMR deficiency in ovarian cancer, an isogenic cell line model of MMR deficiency was established by stable transfection of a plasmid for MLH1 and its corresponding empty vector into SKOV3 cells. The MLH1+ cell line SAC-1 and MLH1- cell line SN-5 were selected for drug screening based on their phenotype and growth rate. The AlamarBlue assay, with z’ above 0.5, was chosen for drug screening and a kinase inhibitor library containing 362 drugs of known target was screened. Two drugs with similar structures that targeted PLK1 showed greater growth inhibition of SN-5 compared with SAC-1. When the two cell lines were treated with another PLK1 inhibitor, BI2536, with different structure, a 2-fold difference in growth inhibition between SAC-1 and SN-5 was also observed, suggesting PLK1 is a potential synthetic lethal target for MLH1 deficiency in ovarian cancer. Together these data demonstrate that clinically, MMR deficiency is associated with non-serous subtypes of ovarian cancer and specific MMR proteins are paired in loss. While current standard therapy offers no selective benefit to ovarian cancer patients with MMR deficiency, inhibiting PLK1 activity may confer selective benefit.

Master of Science / Journalism and Mass Communications / Curtis B. Matthews / Health communication messages have been found to have a significant positive impact on audiences. However, numerous situations exist in which the general population is exposed to information from non-credible sources. This initial exposure can often bias or impact subsequent searching for more information. Vaccinations have been considered effective as a result of the number of lives that have been saved by preventing life threatening diseases. However there is also a growing group of anti-vaccine sources. The rise of the internet has resulted in the growth of numerous unqualified anti-vaccine sources. Nearly 70% of the health information that people find on the internet is from non-credible sources. These messages often take the form of videos in which a person who makes a passionate claim about the side effects of vaccines uses personal experiences (exemplars). These exemplars are used to counter the volumes of scientific and clinical research which show the effectiveness of vaccinations (base-rate information). This study manipulates the usage of passionate and dispassionate exemplars and base-rate information by simulating a real-world situation. Passionate exemplars were the most likely to create fear in our audience. Increasing the passion of our base-rate presenters exhibited both positive and negative side effects.

During the first year of life, infants go from perceiving speech sounds primarily based on their acoustic characteristics, to perceiving speech sounds as belonging to speech sound categories relevant in their native language(s). The transition is apparent in that very young infants typically discriminate both native and non-native speech sound contrasts, whereas older infants show better discrimination for native contrasts and worse or no discrimi­na­tion for non-native contrasts. The rate of this perceptual reorganization depends, among other things, on the salience of the relevant speech sounds within the speech signal. As such, the perceptual reorganization of vowels and lexical tone typically precedes the perceptual reorganization of consonants. Perceptual reorganizatoin of speech sounds is often demonstrated by measuring in­fants’ discrimination of specific speech sound contrasts across development. One way of measuring discriminatory ability is to use the mismatch response (MMR). This is a brain response that can be measured using external electroencephalography re­cord­ings. Pre­senting an oddball (deviant) stimulus among a series of standard stimuli elicits a response that, in adults, correlates well with behavioral discrimination. When the two stimuli are speech sounds contrastive in the listeners’ language, the response arguably reflects both acoustic and linguistic processing. In infants, the response is less studied, but has nevertheless already proven useful for studies on the perceptual reorganization of speech sounds. The present thesis documents a series of studies with the end game of investigating how amount of speech exposure influences the perceptual reorganization, and whe­ther the learning mechanisms involved in speech sound cate­gory learning is specific to speech or domain-general. In order to be able to compare MMR results across diffe­rent age groups in infancy, a non-speech control condition needed to be devised however, to account for changes in the MMR across development that are attributable to general brain matura­tion rather than language development specifically. Findings of studies incorporated in the thesis show that spectrally rotated speech can be used to approximate the acoustic part of the MMR in adults. Subtracting the acoustic part of the MMR from the full MMR thus estimates the part of the MMR that is linked to linguistic, rather than acoustic, processing. The strength of this linguistic part of the MMR in four- and eight-month-old infants is directly related to the daily amount of speech that the infants are exposed to. No evidence of distributional learning of non-speech auditory categories was demonstrated in adults, but the results together with previous research generated hypo­theses for future study. In conclusion, the research performed within the scope of this thesis highlight the need of a non-speech control condition for use in developmental speech perception studies using the MMR, demonstrates the viability of one such non-speech control condition, and points toward relevant future research within the topic of speech sound category development. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

No description available.

This dissertation is an examination of trust in vaccine science, with a focus on ideas about vaccination outside the scientific consensus. It is grounded in empirical research, including 35 interviews and a review of publicly available documents, books, and academic articles. Theoretically, it is informed by theories in the sociology of science, social movements, and the sociology of expertise. In substantive chapters, it investigates the origins of the modern ‘anti-vaccine’ movement, the spread of the movement's ideas in different sociocultural and political contexts, and the perspectives and personal experiences of those who are part of the movement. Overall, it contributes to a growing body of literature that aims to change the conversation around vaccine hesitancy from an information-deficit problem to an issue about trust in institutions. The dissertation is organized into three main papers. The first is an analysis of a specific historic episode, namely the 1998 MMR (measles, mumps, rubella) vaccine-autism controversy. I find that institutional incentive structures unintentionally circulated misinformation about the MMR vaccine by former medical doctor Andrew Wakefield and posit the role that academic reward structures have in fostering public trust. The second paper examines vaccine hesitancy with a social movement lens, specifically focusing on the strategies used by the anti-vaccine movement to organize and frame their message. I introduce the concept of an ‘anti-scientific intellectual movement’ to understand the increasing trend of social groups opposing science as a set of institutions. The third paper is a study of the lived experiences of participants who were interviewed in 2019 about their views on vaccination and how their individual experiences and meaning-making activities impacted their trust in vaccine science. I find strong distrust in scientific institutions, a desire for open dialogue and debate, and dissatisfaction with the ‘anti-vaccine’ label which participants felt erased the nuance in their perspectives. Altogether, this dissertation makes significant contributions to ongoing discussions about the public face of science and how to effectively engage with public audiences to build trust. / Dissertation / Candidate in Philosophy

This doctoral thesis describes unusual skin and soft-tissue tumors, which were the basis of the postgraduate study of Ladislav Hadravský, MD at Medical faculty in Pilsen of Charles University in Prague during 2013 - 2016. It contains documented cases of skin and soft-tissue tumors related to hereditary syndromes, unusual morphology, rare biological behavior, minor causal association with the respective disease, or different phenotypes. These cases were published in journals with the impact factor and in peer-reviewed journals. Regarding skin tumors, the study focused on sebaceous tumors of the skin, which may occur within Muir-Torre syndrome. In the retrospective study of sebaceous skin tumors, two unusual cases were found: the case of aggressive extraocular sebaceous carcinoma on the scalp in a patient with Muir-Torre syndrome and the case of multiple sebaceous skin tumors in a patient with MUTYH-associated polyposis of the colon mimicking Muir-Torre syndrome. As far as soft-tissue tumors are concerned, the study aimed at the morphological comparison of cases of myxoinflammatory fibroblastic sarcoma and pleomorhic hyalinizing angiectatic tumor.

This doctoral thesis describes unusual skin and soft-tissue tumors, which were the basis of the postgraduate study of Ladislav Hadravský, MD at Medical faculty in Pilsen of Charles University in Prague during 2013 - 2016. It contains documented cases of skin and soft-tissue tumors related to hereditary syndromes, unusual morphology, rare biological behavior, minor causal association with the respective disease, or different phenotypes. These cases were published in journals with the impact factor and in peer-reviewed journals. Regarding skin tumors, the study focused on sebaceous tumors of the skin, which may occur within Muir-Torre syndrome. In the retrospective study of sebaceous skin tumors, two unusual cases were found: the case of aggressive extraocular sebaceous carcinoma on the scalp in a patient with Muir-Torre syndrome and the case of multiple sebaceous skin tumors in a patient with MUTYH-associated polyposis of the colon mimicking Muir-Torre syndrome. As far as soft-tissue tumors are concerned, the study aimed at the morphological comparison of cases of myxoinflammatory fibroblastic sarcoma and pleomorhic hyalinizing angiectatic tumor.

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