Objective: The objective of this thesis was to estimate the impact on newborn screening (NBS) results of changing screening technology from tandem mass spectrometry (MS/MS) to an approach using targeted next-generation sequencing (T-NGS) and MS/MS in parallel. Methods: We integrated results of an analysis of MS/MS screening data for phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency; and a query of genetic compendia for variants of genes associated with the two disorders. Results: The introduction of T-NGS into NBS may reduce nearly 80% of false positives that are generated using the current screening approach. Based on estimated NBS results, T-NGS may be applied using a second-tier approach, which may improve specificity while maintaining sensitivity at its current level. Discussion: T-NGS may enhance the performance of NBS for PKU by improving specificity when used as a second tier test, but may be limited by feasibility and cost under current circumstances. Future studies should consider the cost-effectiveness of T-NGS for all infants undergoing NBS.

A comprehensive molecular and phenotypic analysis of congenital and childhood cataractRachel L. Gillespie; The University of Manchester, Doctor of Philosophy, 2015Congenital and childhood cataract (CCC) is estimated to affect 3.5-6 per 10,000 children under 16 years in developed countries - a major cause of lifelong visual impairment. It is estimated that 25-50% of CCC cases are caused by genetic mutations. CCC demonstrates extreme heterogeneity with more than 100 associated genes, and may occur as an isolated anomaly of the eye (non-syndromic) or as a manifestation of a multisystem condition (syndromic). Limitations of conventional sequencing technologies have precluded precise genetic diagnosis and limited understanding of the epidemiological basis of the condition. Next generation sequencing (NGS) technologies have revolutionised the approach to the study of human disease. The aim of this research was to conduct a comprehensive molecular and phenotypic analysis of CCC using NGS.A disease-targeted NGS assay was designed to screen, in parallel, 115 genes associated with all forms of CCC. DNA from 36 patients, randomly selected from the study cohort, underwent cataract-targeted NGS. Putative cataract-causing variants were identified in 75% of individuals; 85% of non-syndromic patients and 63% of syndromic CCC patients. Cataract-targeted NGS was able to efficiently delineate disease sub-type and in some cases identified rare syndromic forms of the condition. These findings were envisaged to alter care and management of CCC patients demonstrating the potential clinical utility of the test. In a subset of cases, NGS identified CCC was a manifestation of an inborn error of metabolism. A number of these conditions were eligible for preventative treatment emphasizing the importance of early diagnosis. A strategic approach to the identification of novel recessive causes of CCC was also undertaken. Affected children from seven consanguineous families underwent pre-screening by cataract-targeted NGS to delineate those with mutations in known genes. Mutation negative patients underwent autozygosity-guided whole exome sequencing (WES) analysis. This strategic approach to disease gene discovery led to the identification three novel cataract-causing candidate genes, TRIM8, CCDC13 and GRWD1. It also led to the association of EIF2B2, known to cause adult-onset leukoencephalopathy with vanishing white matter (VWM) disease featuring pre-senile onset cataract, with childhood-onset cataract. This work demonstrated that cataract-targeted NGS offers an efficient and unbiased means of pre-screening, however, causation is difficult to assign to novel disease genes in the absence of experimental evidence. Correspondingly, in vitro analysis of a missense variant in HMX1 demonstrated the deleterious effect of the mutation on protein function. This work confirmed HMX1 as the cause of a rare oculoauricular phenotype and expanded the class of disease-causing mutations in this gene. In conclusion, this study has demonstrated that NGS is effective in the study of CCC and has provided a platform for future studies in to the genetic aetiology of the condition, as well as the molecular mechanisms underlying lens transparency and human development. The work adds to the increasing body of evidence that augurs an era of personalised genomic medicine in ophthalmology that will foresee improved patient outcomes attributable to the implementation of a stratified approach to medicine.

The diploma thesis analyzes the loyalty program at Next PK Ltd. and is focused on research of the loyalty program of this company. Its aim is to analyze the loyalty program and its perception by the loyalty customers. The thesis is divided into six parts -- an introduction, a part about Next PK s.r.o., a theoretical part, a methodological part, a practical part and a conclusion. The theoretical part consists of characteristic of satisfaction, loyalty and loyalty programs. The methodology section describes the method of investigation and also the methodology for evaluating the research. The practical part consists of a survey among loyalty customers in Next where the goal is to analyze the customers' satisfaction or dissatisfaction. The conclusion contains a summary of the investigation and recommendations regarding functioning of the loyalty program Next.

Knowledge of the diet of wildlife can aid wildlife biologists to better understand how a species functions within a given ecosystem. Numerous studies have identified various avenues to examine diet for species throughout the world. Wildlife biologists have used diet composition variables as a means to better understand habitat use and aid in the management and conservation of mule deer, Odocoileus hemionus. The complexity of deer diet is still unknown, and local wildlife management agencies could improve conservation strategies with more information regarding the breadth of plant selection in deer diet. Researchers have used non-invasive methods, such as microhistology via fecal analyses, to assess diet composition for mule deer. However, microhistology has several drawbacks that include accuracy in identification and differentiation of plant species, and even genus, as well as determination of accurate proportions of taxa ingested. Genetic techniques, such as next-generation sequencing (NGS), present new avenues for analyzing herbivore diets, especially through the amplification and analyses of specific regions of chloroplast DNA (cpDNA). Additionally, few studies have directly compared microhistological and NGS diet analyses results for any wildlife species. My objectives were to compare diet composition results of both microhistological and NGS diet analyses through estimating diet richness, taxonomic resolution, percent diet, and frequency of occurrence of plant taxa across samples. Mule deer fecal samples were collected on the Navajo Nation from summer and winter ranges of two distinct mule deer populations, Chuska and Carrizo. I found far greater richness and resolution from NGS of plant taxa through the identification of a greater number of species and genera among all populations, within seasons. Upon testing both methods for both populations, no significant agreement was identified for percent of families identified in the diet with both methods, across all samples. I found trends of positive correlation in the occurrence of families between both methods for Carrizo summer diet, as well as among genera and families in Carrizo winter diet. Upon further statistical analyses, I found no significant positive correlation in the occurrence of genera and families identified with both methods among all samples. Genetic techniques may present innovative methods for determining mule deer diet in various ecosystems, and may also be applied to a broad range of herbivore diet studies.

The study of the angular distribution of photon plus jet events in pp collisions at √S =7 TeV with the Compact Muon Solenoid (CMS) detector is presented. The photon is restricted to the central region of the detector (|η| < 1.4442) while the jet is allowed to be present in both central and forward regions of CMS |η| < 2.4). Dominant backgrounds due to jets fragmenting into neutral mesons are accounted for through the use of a template method that discriminates between signal and background. The angular distribution, |η*|, is defined as the absolute value of the difference in η between the leading photon and leading jet in an event divided by two. The angular distribution ranging from 0-1.4 was examined and compared with next-to-leading order QCD predictions and was found to be in good agreement.

Dezoito galinhas de uma população experimental utilizada em um cruzamento recíproco entre as linhagens de frangos de corte (TT) e de postura (CC) foram sequenciadas pela tecnologia de nova geração na plataforma Illumina com uma cobertura média de 10X. A descoberta de variantes genéticas foi realizada em uma região de locos de característica quantitativa (Quantitative Trait Locus, QTL), associado anteriormente com peso e percentagem de gordura abdominal no cromossomo 3 da galinha (GGA3), entre os marcadores microssatélites LEI0161 e ADL0371 (33,595,706-42,632,651 pb). O programa SAMtools foi utilizado na identificação de 136.054 SNPs únicos e 15.496 INDELs únicas nos 18 animais sequenciados e após a filtragem das mutações, 92.518 SNPs únicos e 9.298 INDELs únicas foram mantidas. Uma lista de 77 genes foi analisada buscando genes relacionados ao metabolismo de lipídios. Variantes localizadas na região codificante (386 SNPs e 15 INDELs) foram identificadas e associadas com vias metabólicas importantes. Variantes nos genes LOC771163, EGLN1, GNPAT, FAM120B, THBS2 e GGPS1 foram identificadas e podem ser responsáveis pela associação do QTL com a deposição de gordura na carcaça em galinhas. / Eighteen chickens from a parental generation used in a reciprocal cross with broiler and layer lines were sequenced by new generation technology with an average of 10-fold coverage. The DNA sequencing was performed by Illumina next generation platform. The genetic variants discovery was performed in a quantitative trait loci (QTL) region which was previously associated with abdominal fat weight and percentage in chicken chromosome 3 (GGA3) between the microsatellite markers LEI0161 and ADL0371 (33,595,706-42,632,651 bp). SAMtools software was used to detect 136,054 unique SNPs and 15,496 unique INDELs for the 18 chickens, and after quality filtration 92,518 unique SNPs and 9,298 unique INDELs were retained. One list of 77 genes was analised and genes related to lipid metabolism were searched. Variants located in coding region (386 SNPs and 15 INDELs) were identified and associated with important metabolic pathways. Loss of functional variants in the genes LOC771163, EGLN1, GNPAT, FAM120B, THBS2 and GGPS1 may be responsible for the QTL associated with fat deposition in chicken.

Bakgrund: Cancer drabbar årligen mer än 50 000 familjer och när en person insjuknar drabbas alla runtomkring. Cancervård är en stor del av svensk sjukvård och har flera aktörer som patienter, närstående och sjukvårdspersonal. Cancervården innefattar många aspekter som diagnosbesked, behandling och psykosocialomvårdnad samt vilka aktörer som är involverade i de olika faserna och hur de ser på delaktighet. Syfte: Syftet med litteraturstudien var att belysa närståendes upplevelser av delaktighet vid cancervård.Metod: En litteraturstudie baserad på 10 vetenskapliga artiklar med kvalitativ ansats för att få fram ett resultat. De valda artiklarna relevans- och kvalitetsgranskades med hjälp av SBU:s mall för kvalitetsgranskning av studier med kvalitativ forskningsmetodik. Detta resulterade i sex artiklar med hög kvalitet och fyra artiklar av medel kvalitet. Databassökningar utfördes i CINAHL och PubMed. Resultat: Studien gav en bred bild av närståendes upplevelser av delaktighet och resultatet presenteras i fyra kategorier: Kommunikationens betydelse, känsla av otillräcklighet, delaktighet genom stöttning och att bli inkluderad.Konklusion: Närstående är en viktig del i vården av personer diagnosticerade med cancer. Närstående upplever i viss mån att de är inkluderade men att sjukvården bör bli ännu bättre på att inkludera dem. Sjukvården behöver bli bättre på att kommunicera och bli bättre på att se vad närstående behöver. / Background: Cancer affects more than 50 000 families every year and when a person is diagnosed everyone around is affected. Cancer care is a big part of the Swedish health care system and has multiple participants, such as patients, health care professionals and next of kin. Cancer care has many aspects, delivering the diagnosis, treatment and psychosocial care and who participates in what part.Aim: The aim with the literature review was to illuminate the next of kin perception of participation in cancer care.Method: A literature review based on 10 scientific articles with a qualitative approach to get a result. The chosen articles were reviewed for quality with the help of SBU:s reviewing templet. This resulted in six articles with high quality and four articles with medium quality. The database searches were performed in CINAHL and PubMed. Result: The review provided a broad picture of the next of kin experiences of participation and the result is presented in four separate categories: Communication, feeling of inadequacy, participation through support and to be included.Conclusion: Next of kin are an important part of the care of people diagnosed with cancer. Next of kin has a perception of participation to a certain degree, but the health care system needs to be more inclusive of next of kin, they need to improve their communication skills and to see what needs next of kin has.

Andersson, L & Milton, N. Upplevelser av att vara närstående till en person med cancer. En litteraturstudie i omvårdnad. Examensarbete i omvårdnad 15 högskolepoäng. Malmö universitet: Fakulteten för hälsa och samhälle, institutionen för vårdvetenskap, 2020.Bakgrund: Antalet personer som drabbas av cancer ökar och därmed även antalet närstående till personer med cancer. Tidigare studier påvisar vikten av att patienter med cancer har en närstående. Vidare visade en studie att de närstående som var involverade i patientens vård själva hade ett ökat vårdbehov. Det framkom även från en studie att det fanns samband mellan sjuksköterskors självsäkerhet och deras bemötande av närstående. Utifrån studierna kan kunskap om närståendes upplevelser behöva utvecklas för att kunna förbättra vården för närstående och eventuellt även för patienterna.Syfte: Syftet med litteraturstudien var att sammanställa upplevelser av att vara närstående till en person med cancer.Metod: Uppsatsen är baserad på en litteraturstudie med kvalitativ ansats. Inklusionskriterier och exklusionskriterier genomfördes. Vidare gjordes sökningar i databaserna PubMed och Cinahl. Studiernas kvalitet granskades utifrån SBU:s kvalitetsgranskningsmall och analyserades med hjälp av Graneheim och Lundmans innehållsanalys. Slutligen återstod 13 studier som användes i föreliggande litteraturstudie.Resultat: Resultatet består av tre huvudkategorier vilka är upplevelser av behov, känslor och strategier samt förändrad relation. Samtliga huvudkategorier hade underkategorier och totalt blev det sju underkategorier.Konklusion: Att vara närstående är en komplex situation där flera olika aspekter är inkluderade. För att på bästa sätt kunna bemöta närståendes upplevelser, krävs det att sjuksköterskan har förståelse kring närståendes upplevelser.Nyckelord: Cancer, hantering, närstående, omvårdnad, upplevelser / Andersson, L & Milton, N. Experiences of being the next of kin to a person with cancer. A literature review in nursing. Degree project in nursing 15 Credits. Malmö university: Faculty of Health and Society Department of Care Science, 2020.Background: The number of people affected by cancer increases and thereby also the number of next of kin to people with cancer. Previous studies showed the importance for patients with cancer to have next of kin. Furthermore, a study showed that the next of kin were involved in patients care also had an increasing need for care themselves. In another study the data revealed that there is a connection between nurses’ confidence and their approach to the next of kin. With this in mind there is a need for knowledge about the next of kin’s experiences, to try to improve the care for next of kin and perhaps also for the patients.Aim: To compile studies about next of kin’s experiences about being the next of kin to a person with a cancer diagnosis.Method: The literature study is based on a qualitative approach. Inclusion criterias and exclusion criterias were made. Furthermore, searches were made in the databases PubMed and Cinahl. The quality of the studies were examined with SBU:s reviewed templet and the content were then analysed by using Graneheim and Lundman’s analysis model. Finally, only 13 studies remained.Results: The result is based on three headlines which are the experiences of needs, emotions and strategies and changed relationship. All of the headline’s hade subheadings and in total there were seven subheadings.Conclusion: To be the next of kin is a complex situation, with many different aspects. In order to best deal with the situation of the next of kin, it is necessary that the nurse understands the next of kin’s experiences.Keywords: Cancer, experiences, handling, next of kin, nursing.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22002号 / 医博第4516号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 滝田 順子, 教授 松田 文彦, 教授 山田 亮 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22011号 / 工博第4623号 / 新制||工||1720(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 酒井 伸一, 教授 高岡 昌輝, 准教授 平井 康宏 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM