Bakgrund: I Sverige drabbas mer än 50000 personer av cancer varje år. Ca 35 % av all cancer går inte att bota, och vården blir palliativ. Även de närstående påverkas, och är i behov av stöd från sjukvården. Syfte: Syftet med studien var att undersöka upplevelsen och behovet av stöd inom den onkologiska slutenvården för närstående till patienter med cancer i palliativt skede som inte är anslutna till hemsjukvård eller hospice. Metod: Studien är utförd utifrån en kvalitativ ansats och är baserad på sju intervjuer där resultatet har bearbetats med stöd av en kvalitativ innehållsanalys. Resultat: Närstående upplever sig i stort erhålla ett gott stöd från den onkologiska slutenvården. Viktigast upplevs att som närstående bli sedd och bekräftad, samt att erhålla lagom mängd information löpande under vårdtiden. Detta, tillsammans med ett gott stöd från familj och vänner, gör att närstående känner sig trygga. Det som främst upplevs saknas är chansen till avskildhet, samt tydligare information om vart man kan vända sig vid eventuellt behov av hjälp efter hemgång. Även någon form av kontaktperson efterfrågas för att minska känslan av att känna sig utlämnad och vilsen. Slutsats: Dagens slutenvård upplevs ge ett gott stöd till närstående inom den palliativa cancervården. För att sjuksköterskan ska känna sig trygg i sin profession, och orka driva utvecklingen inom vården framåt, krävs kontinuerlig fortbildning.

Bakgrund: I Sverige drabbas mer än 50000 personer av cancer varje år, men det är inte bara patienten som drabbas utan även alla närstående. Ca 35 % av all cancer går inte att bota och vården blir palliativ, vilken syftar till att förebygga och lindra lidandet för patienten och dennes familj. Att vara närstående i denna situation framkallar många olika känslor. Syfte: Syftet med studien är att belysa upplevelsen av att vara närstående till en palliativ patient med cancer. Metod: Studien är utförd utifrån en kvalitativ ansats och är baserad på sex biografier där resultatet har bearbetats med stöd av en kvalitativ innehållsanalys. Resultat: Upplevelsen av att vara närstående till en patient med cancer tar fram många motstridiga känslor såsom oro, hopp, vanmakt och frid. Vikten av att som närstående få bekräftelse från såväl den sjuke som från vården belyses, liksom vikten av att få stöd och hjälp från vården för att orka vara den starka som alltid finns där. Betydelsen av familj och vänner belyses också. Slutsats: Studien visar tydligt att vården måste bli bättre att i ett tidigt skede möta upp de närstående och även se deras behov. Hur viktigt det är med information, att få veta vad som kommer att hända, vad som kan förväntas och vilken hjälp man kan få. Många upplever att man får den hjälp och stöd man behöver först när den palliativa vården kopplas in. / Background: In Sweden, more than 50,000 people is affected of cancer every year, but it's not just patients who are affected it is also next-of-kin. About 35 % of all cancers cannot be cured and the treatment is palliative, which seeks to prevent and alleviate the suffering of the patient and their family. To be next-of-kin in this situation evokes many feelings.Purpose: The aim of this study is to illuminate the experience of being next-of-kin to a palliative patient with cancer.Method: The study was conducted based on a qualitative approach and is based on six biographies where the results have been processed by means of a qualitative content analysis.Results: The experience of being next-of-kin to a patient with cancer brings out many feelings such as anxiety, hope, despair, and peace. The importance as a next-of-kin to be confirmed from the patient and the healthcare is elucidated, as well as the importance of getting help and support from the health care system to cope and to be the strong one who is always there for the patient. The importance of family and friends is also highlighted.Conclusion: This study clearly shows that healthcare must be much better at an early phase to see the family and also to see their needs. The importance of information, to know what will happen, what can be expected and what help you can get. Many feel that they first receive the help and support they need when palliative care is a reality.

Three statistical models are developed to address problems in Next-Generation Sequencing data. The first two models are designed for RNA-Seq data and the third is designed for ChIP-Seq data. The first of the RNA-Seq models uses a Bayesian non- parametric model to detect genes that are differentially expressed across treatments. A negative binomial sampling distribution is used for each gene’s read count such that each gene may have its own parameters. Despite the consequent large number of parameters, parsimony is imposed by a clustering inherent in the Bayesian nonparametric framework. A Bayesian discovery procedure is adopted to calculate the probability that each gene is differentially expressed. A simulation study and real data analysis show this method will perform at least as well as existing leading methods in some cases. The second RNA-Seq model shares the framework of the first model, but replaces the usual random partition prior from the Dirichlet process by a random partition prior indexed by distances from Gene Ontology (GO). The use of the external biological information yields improvements in statistical power over the original Bayesian discovery procedure. The third model addresses the problem of identifying protein binding sites for ChIP-Seq data. An exact test via a stochastic approximation is used to test the hypothesis that the treatment effect is independent of the sequence count intensity effect. The sliding window procedure for ChIP-Seq data is followed. The p-value and the adjusted false discovery rate are calculated for each window. For the sites identified as peak regions, three candidate models are proposed for characterizing the bimodality of the ChIP-Seq data, and the stochastic approximation in Monte Carlo (SAMC) method is used for selecting the best of the three. Real data analysis shows that this method produces comparable results as other existing methods and is advantageous in identifying bimodality of the data.

Το περιεχόμενο του συγκράματος ασχολείται με τη μελέτη αρχιτεκτονικών διαστρωμάτωσης για τη διερεύνηση των λειτουργικών απαιτήσεων των ασύρματων δικτύων επόμενης γενιάς. Αφού γίνει η μελέτη των τεχνικών καταχώρισης συχνοτήτων στα κυτταρικά συστήματα των κινητών επικοινωνιών κατόπιν αναλύονται οι λειτουργικές διαδικασίες των κυτταρικών συστημάτων κινητής τηλεφωνίας όπως και το μοντέλο καταχώρισης ραδιοπόρων το οποίο βασίζεται στις τεχνικές Erlang. Ακολούθως προτείνονται μέσω μαθηματικής ανάλυσης διεπίπεδες τεχνικές μεταγωγής. Εν συνεχεία, παρουσιάζεται η εφαρμογή της πολυεπίπεδης αρχιτεκτονικής στα σύγχρονα κυτταρικά συστήματα όπου αναλύεται η αρχιτεκτονική UMTS/HAP. Στα αποτελέσματα της προσομοίωσης που κάνουμε στο σύστημα μας, παρατηρούμε την αισθητή μείωση της dropping/blocking πιθανότητας όταν εφαρμοστεί η προτεινόμενη τεχνική. / The subject of diploma is about studying architectures of multilayrer in next generation wireless networks. After we study registration techniques in cellar systems of wireless communication systems, we analyze operating processes of mobile network and sources registration based on Erlang's techniques. after all, it is presented the application of multilayer architecture in modern cell systems where architecture UNTS/HAP is analyzed. In the results of our simulation we see that the blocking/dropping probability is decreased when out technique is enabled

<p><p>Eukaryotic genomes have extensive flexibility and plasticity to modify transcription and replication programs, yielding a myriad of differentiated cell types and survival mechanisms to adverse environmental conditions. As these genomic processes require precise localization of DNA-binding factors, their dynamic temporal and spatial distributions provide dramatically different interpretations of a static genome sequence. DNA-binding factors must compete with nucleosomes, the basic subunit of chromatin, for access to the underlying DNA sequence. Even though the spatial preferences of these proteins are partially explained by DNA sequence alone, the complete genome occupancy profile has remained elusive, and we currently have a limited understanding of how DNA-binding protein configurations directly impact transcription and replication function.</p></p><p><p>Profiling the entire chromatin environment has typically required multiple experiments to capture both DNA-binding factors and nucleosomes. Here, we have extended the traditional micrococcal nuclease (MNase) digestion assay to simultaneously resolve both nucleosomes and smaller DNA-binding footprints in <i>Saccharomyces cerevisiae</i>. Visualization of protected DNA fragments revealed a nucleotide-resolution view of the chromatin architecture at individual genomic loci. We show that different MNase digestion times can capture nucleosomes partially unwrapped or complexed with chromatin remodelers. Stereotypical DNA-binding footprints are evident across all promoters, even at low-transcribed and silent genes. By aggregating the chromatin profiles across transcription-factor--binding sites, we precisely resolve protein footprints, yielding <i>in vivo</i> insights into protein-DNA interactions. Together, our MNase method, in one experiment, provides an unprecedented assessment of the entire chromatin structure genome-wide.</p></p><p><p>We utilized this approach to interrogate how the replication program is regulated by the chromatin environment surrounding DNA replication initiation sites. Pre-replicative complex (pre-RC) formation commences with recruitment of the origin recognition complex (ORC) to specific locations in the genome, termed replication origins. Although successful pre-RC assembly primes each site for S-phase initiation by loading the Mcm2-7 helicase, replication origins have substantially different activation times and efficiencies. We posited that replication origin function is substantially impacted by the local chromatin environment. Here, we resolved a high-resolution ORC-dependent footprint at 269 replication origins genome-wide. Even though ORC in <i>S. cerevisiae</i> remains bound at replication origins throughout the cell cycle, we detected a subset of inefficient origins that did not yield a footprint until G1, suggesting a more transient ORC interaction prior to pre-RC assembly. Nucleosome movement accommodated the pre-RC-induced expansion of the ORC-dependent footprint in G1, leading to increased activation efficiency. Mcm2-7 loading is preferentially directed to one side of each replication origin, in close proximity to the origin-flanking nucleosome. Our data demonstrates that pre-RC components are assembled into multiple configurations <i>in vivo</i>.</p></p><p><p>We anticipate that extending chromatin occupancy profiling to many different cell types will reveal further insights into genome regulation.</p></p> / Dissertation

O objetivo deste trabalho foi caracterizar os mecanismos adquiridos de resistência de isolados de enterobactérias produtoras de carbapenemases utilizando a tecnologia de sequenciamento de nova geração. Foram incluídos no estudo quatro isolados – três Escherichia coli e uma Serratia marcescens – produtores de diferentes carbapenemases – OXA-370, KPC-2, NDM-1 e GES-5, respectivamente, obtidos a partir de um estudo de vigilância para detecção de carbapenemases. O DNA total dos isolados foi extraído utilizando kits comerciais e submetido à fragmentação enzimática para a obtenção de bibliotecas genômicas de aproximadamente 300 pares de bases. Após a preparação das bibliotecas, elas foram carregadas em chips 316 v2 para a plataforma Ion Torrent PGM e submetidas ao sequenciamento, utilizando um programa de 850 flows. Para cada genoma, foram obtidos aproximadamente um milhão de reads, os quais foram submetidos ao processo de montagem para a obtenção de genomas de aproximadamente 5Mb com uma cobertura de, em média, 175 vezes. As sequências obtidas foram submetidas à anotação utilizando o sistema RAST e a ferramenta online ResFinder. Sequências de inserção foram pesquisadas utilizando a ferramenta ISFinder. Além das carbapenemases, genes que codificam para outras β-lactamases (blaTEM-1, blaCTX-M-2 blaCTX-M-8, blaOXA-1, blaOXA-2) foram encontrados em todos os genomas. AMEs (aadA1, aph(3’)-la, aac(3)-IIa, strA, strB, aac(6’)Ib-cr, aac(6’)-Ib and aac(6`)-Ic), bem como genes que codificam resistência às sulfonamidas e ao trimetoprim também foram comuns aos isolados avaliados. Os seguintes ambientes genéticos foram observados: blaOXA-370 é flanqueada pela IS5075-like, blaKPC-2 está inserida no transposon Tn4401, e blaNDM-1, no transposon Tn3000. Cada isolado de E. coli pertenceu a um sequence type (ST) distinto: 1099F pertence à ST617, 1326F, à ST648, e 2610F, à ST707. Nossos resultados indicaram a diversidade de genes de resistência que podem ser encontrados em um isolado clínico, ressaltaram a variedade de contextos genéticos em que as carbapenemases podem estar inseridas e demonstraram que o sequenciamento de nova geração pode ser utilizado como uma ferramenta para a caracterização de isolados bacterianos multirresistentes, auxiliando, entre outros aspectos, na tipagem e na identificação de determinantes de resistência. / The aim of this study was to characterize the resistome of carbapenemase-producing Enterobacteriaceae using a next-generation sequencing platform. Four isolates were included in this study – three Escherichia coli and one Serratia marcescens – producing different carbapenemases – OXA-370, KPC-2, NDM-1 and GES-5, respectively, obtained from a surveillance study for carbapenemase detection. Total DNA was extracted using commercially available kits and submitted to enzymatic fragmentation to obtain libraries of around 300 base pairs of each isolate. After library preparation, they were loaded in 316 v2 chips for Ion Torrent PGM platform, and sequencing was performed using an 850 flows program. For each genome, approximately a million reads were obtained, and they were further assembled. The genome length for each isolate was of around 5Mb, with a mean coverage of 175x. The RAST system and the online tool ResFinder were used for annotation, as well as ISFinder. Besides the carbapenemases, genes encoding for other β-lactamases (blaTEM-1, blaCTX-M-2 blaCTX-M-8, blaOXA-1, blaOXA-2) were found in all genomes. AMEs (aadA1, aph(3’)-la, aac(3)-IIa, strA, strB, aac(6’)Ib-cr, aac(6’)-Ib and aac(6`)-Ic) were also detected in every isolate included in the study, as well as genes encoding for resistance determinants to sulfonamides and trimetoprim. The genetic environment of the carbapenemases was very similar to other isolates described in the literature – blaOXA-370 is flanked by IS5075-like, blaKPC-2 is inserted in transposon Tn4401, and blaNDM-1 was found in transposon Tn3000. Each isolate belonged to a distinct ST – 1099F is part of ST617, 1326F belonged to ST648 and 2610F, to ST707. Our results demonstrated the diversity of resistance determinants that can be found in a clinical isolate, highlighted the variability of genetic environments in which carbapenemases can be present and demonstrated that next-generation sequencing is a valuable tool for the characterization of multidrug-resistant isolates, and can provide information regarding the molecular typing and the identification of resistance determinants.

O objetivo deste trabalho foi caracterizar os mecanismos adquiridos de resistência de isolados de enterobactérias produtoras de carbapenemases utilizando a tecnologia de sequenciamento de nova geração. Foram incluídos no estudo quatro isolados – três Escherichia coli e uma Serratia marcescens – produtores de diferentes carbapenemases – OXA-370, KPC-2, NDM-1 e GES-5, respectivamente, obtidos a partir de um estudo de vigilância para detecção de carbapenemases. O DNA total dos isolados foi extraído utilizando kits comerciais e submetido à fragmentação enzimática para a obtenção de bibliotecas genômicas de aproximadamente 300 pares de bases. Após a preparação das bibliotecas, elas foram carregadas em chips 316 v2 para a plataforma Ion Torrent PGM e submetidas ao sequenciamento, utilizando um programa de 850 flows. Para cada genoma, foram obtidos aproximadamente um milhão de reads, os quais foram submetidos ao processo de montagem para a obtenção de genomas de aproximadamente 5Mb com uma cobertura de, em média, 175 vezes. As sequências obtidas foram submetidas à anotação utilizando o sistema RAST e a ferramenta online ResFinder. Sequências de inserção foram pesquisadas utilizando a ferramenta ISFinder. Além das carbapenemases, genes que codificam para outras β-lactamases (blaTEM-1, blaCTX-M-2 blaCTX-M-8, blaOXA-1, blaOXA-2) foram encontrados em todos os genomas. AMEs (aadA1, aph(3’)-la, aac(3)-IIa, strA, strB, aac(6’)Ib-cr, aac(6’)-Ib and aac(6`)-Ic), bem como genes que codificam resistência às sulfonamidas e ao trimetoprim também foram comuns aos isolados avaliados. Os seguintes ambientes genéticos foram observados: blaOXA-370 é flanqueada pela IS5075-like, blaKPC-2 está inserida no transposon Tn4401, e blaNDM-1, no transposon Tn3000. Cada isolado de E. coli pertenceu a um sequence type (ST) distinto: 1099F pertence à ST617, 1326F, à ST648, e 2610F, à ST707. Nossos resultados indicaram a diversidade de genes de resistência que podem ser encontrados em um isolado clínico, ressaltaram a variedade de contextos genéticos em que as carbapenemases podem estar inseridas e demonstraram que o sequenciamento de nova geração pode ser utilizado como uma ferramenta para a caracterização de isolados bacterianos multirresistentes, auxiliando, entre outros aspectos, na tipagem e na identificação de determinantes de resistência. / The aim of this study was to characterize the resistome of carbapenemase-producing Enterobacteriaceae using a next-generation sequencing platform. Four isolates were included in this study – three Escherichia coli and one Serratia marcescens – producing different carbapenemases – OXA-370, KPC-2, NDM-1 and GES-5, respectively, obtained from a surveillance study for carbapenemase detection. Total DNA was extracted using commercially available kits and submitted to enzymatic fragmentation to obtain libraries of around 300 base pairs of each isolate. After library preparation, they were loaded in 316 v2 chips for Ion Torrent PGM platform, and sequencing was performed using an 850 flows program. For each genome, approximately a million reads were obtained, and they were further assembled. The genome length for each isolate was of around 5Mb, with a mean coverage of 175x. The RAST system and the online tool ResFinder were used for annotation, as well as ISFinder. Besides the carbapenemases, genes encoding for other β-lactamases (blaTEM-1, blaCTX-M-2 blaCTX-M-8, blaOXA-1, blaOXA-2) were found in all genomes. AMEs (aadA1, aph(3’)-la, aac(3)-IIa, strA, strB, aac(6’)Ib-cr, aac(6’)-Ib and aac(6`)-Ic) were also detected in every isolate included in the study, as well as genes encoding for resistance determinants to sulfonamides and trimetoprim. The genetic environment of the carbapenemases was very similar to other isolates described in the literature – blaOXA-370 is flanked by IS5075-like, blaKPC-2 is inserted in transposon Tn4401, and blaNDM-1 was found in transposon Tn3000. Each isolate belonged to a distinct ST – 1099F is part of ST617, 1326F belonged to ST648 and 2610F, to ST707. Our results demonstrated the diversity of resistance determinants that can be found in a clinical isolate, highlighted the variability of genetic environments in which carbapenemases can be present and demonstrated that next-generation sequencing is a valuable tool for the characterization of multidrug-resistant isolates, and can provide information regarding the molecular typing and the identification of resistance determinants.

The afflictions suffered by immunocompromised individuals have historically been attributed to overt infections caused by bacterial and fungal pathogens. For this reason, treatment methods have focused on resolving these infections, with great success in terms of reducing short-term morbidity and mortality rates. This initial success only served to reinforce the dogmatic opinion that to ‘cure’ immunodeficiency, one needs only to resolve and prevent recurrence of bacterial and fungal infections. However, reports of long-term health problems in immunocompromised cohorts suggest that treatment of bacterial and fungal infections alone does not resolve all aspects of the disease, and that viruses may play a greater role than previously expected. This thesis investigates whether viral infections do indeed have a significant impact in the immunocompromised patient. The overall prevalence of blood-borne viral infections in immunocompromised cohorts was determined through the combined use of unbiased, metagenomic sequencing and qPCR. The viral species detected were compared with patient records in order to determine whether there were any correlations between viral presence and patient outcome following treatment. Furthermore, by investigating a cross-section of cohorts with both inherited and acquired immunodeficiences, commonalities and differences could be found in terms of the types of viruses that infect these cohorts and their abundance in patients with different types of immunodeficiency. The findings of this work suggest that a large number of clinically undiagnosed viruses infect immunocompromised patients, however the prevalence of these viruses varies according to the form of immunodeficiency and, to a lesser extent, according to differences between individuals in the same cohort. Importantly, some of the more common viruses detected appear to be correlated with poor patient outcomes such as graft rejection and future infectious complications. Overall, these results suggest that viral infections do indeed play a larger role in the health of immunocompromised patients than has previously been thought although whether this is due to a direct cause or as a consequence is yet to be determined.

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Arruda.pdf: 1036150 bytes, checksum: da9374202f42a247cfc89a0badd0cee2 (MD5) / Made available in DSpace on 2017-08-16T15:05:24Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação - Etienny S. Arruda.pdf: 1036150 bytes, checksum: da9374202f42a247cfc89a0badd0cee2 (MD5) Previous issue date: 2017-04-12 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / The purpose of this study was to evaluate a protocol for endodontic retreatment, using Protaper Next instruments, to evaluate the occurrence of apical transportation using CT. To perform the experiment, 40 mandibular molars were selected, with mesial root canal curvature between 30° and canal curvature radius less than or equal to 10 mm. Size 10 K-type instruments were used to determine the presence of independent foramen. In order to standardize the samples, the crowns were partially sectioned in 16 mm and all the specimens were inserted in resin blocks, to standardize the tomographies in the same position before, during and after instrumentation and retreatment. They were also submitted to the same instrumentation and obturation process, and were then randomly separated (n = 10) into four experimental groups: PTU group, in which the instrument used to remove gutta-percha was Protaper F2 (25.08); Group R25 and Group X2 where the Reciproc - R25 (25.08) and Protaper Next - X2 (25.06) instruments were used for the same purpose, respectively; And Group X3, where the X2 instruments were used sequentially for the removal of gutta-percha and X3 (30.07) for channel remodeling, both belonging to the Protaper Next system. Apical deviation was assessed by applying formulas to values obtained before and after instrumentation, and with the data obtained it was also possible to analyze centering ratio and percentual area increase. Data were subjected to the Kruskal-Wallis Test and the Dunn Multiple Comparisons Test. The results of the apical deviation presented no significant difference between the experimental groups (p <0.05). The methodology and the results lead to the conclusion that the experimental groups did not produce a statistically significant difference in apical deviation. / O objetivo do presente estudo foi avaliar a viabilidade de um protocolo de retratamento endodôntico, utilizando instrumentos Protaper Next, avaliando a ocorrência de transporte apical em raízes mesiais curvas de molares inferiores. Foram selecionados 40 molares inferiores com grau de curvatura da raiz mesial de aproximadamente 30° e raio de curvatura menor ou igual a 10 mm. Com o auxílio de instrumentos tipo K #10, avaliou-se a presença de forames independentes. Com o objetivo de padronizar o as amostras, as coroas foram parcialmente seccionadas em 16 mm e todos os corpos de prova foram inseridos em blocos de resina, para padronização das tomografias na mesma posição antes, durante e após a instrumentação e retratamento. Também foram submetidas ao mesmo processo de instrumentação e obturação, e só depois foram separadas aleatoriamente (n=10) em quatro grupos experimentais: Grupo Protaper Universal (PTU), no qual o instrumento utilizado para a remoção da gutta-percha era a Protaper F2 – 25.08; Grupo Reciproc e Grupo Protaper Next X2 onde para a mesma finalidade eram empregados os instrumentos Reciproc R25 – 25.08 e Protaper Next X2 – 25.06, respectivamente; e o Grupo Protaper Next X3, onde eram utilizados sequencialmente os instrumentos X2 para a remoção da gutta-percha e o X3 (30.07) para remodelação do canal, ambos pertencentes ao sistema Protaper Next. A análise do desvio apical se deu pela aplicação de fórmulas aos valores obtidos antes e após a instrumentação e com os dados obtidos também foi possível analisar o índice de centralização dos intrumentos bem como o aumento percentual da área proporcionado por eles. Os dados obtidos foram submetidos a testes de Kruskall-Wallis e teste de Múltiplas Comparações de Dunn. Os resultados do desvio apical não mostraram diferenças significantes entre os grupos avaliados (p < 0,05). Com base na metodologia empregada e nos resultados obtidos, concluiu-se que não houve, entre os grupos experimentais, diferença significante em relação à produção de desvio apical.

Designprocessen för en ”next-gen”-spelkaraktär är i dag förhållandevis invecklad och innehåller många olika moment innan den når sitt slutgiltiga stadium med en färdig karaktär som resultat. Den här artikeln dokumenterar designprocessen för en spelkaraktär från början till slut och kommer att se mycket till den kreativa men även den tekniska aspekten av detta arbete. Arbetet resulterar i en karaktär som modelleras, skulpteras, animeras och slutligen importeras till Unreal Editor 3.0.