Purpose: The objective of this study was to investigate both depression and psychological distress as determinants of breast and cervical cancer screening. Methods: Ontario female respondents to the Canadian Community Health Survey version 1.2 (2002) were assessed for both Major Depressive Disorder (World Mental Health-Composite International Diagnostic Interview for depression) and psychological distress (Kessler 6-item Distress Scale (K6)>/= 8). Respondents eligible for screening (N=4042 for cervical cancer; N=1403 for breast cancer) were linked to Ontario administrative health service data to prospectively ascertain screening outcomes. Results: Women with K6 >/= 8 had reduced breast cancer screening compliance in adjusted analyses (AOR 0.63, 95% CI 0.40-0.97). The association between K6 >/= 8 and cervical cancer screening approached significance in women over age 40 (AOR=0.65, 95%CI 0.41-1.04). Conclusion: Decreased likelihood of screening in women with clinically significant psychological distress suggests that attention to adequacy of preventive services is a potential target for intervention.

Statement of the problem: Methicillin-resistant Staphyloccocus aureus (MRSA) is a pathogen of increasing concern and is associated with higher hospital readmission rates, poorer prognosis, and increased mortality resulting in increasing costs to the Canadian healthcare system.1-13 Institutions have been challenged with developing effective infection control programs to prevent the spread of MRSA. The purpose of this thesis was to examine the clinical and cost-effectiveness of a universal MRSA screening intervention within a large tertiary care facility. Methods of investigation: The retrospective population-based observational study consisted of two periods. In the first period (24 months), patients admitted to the Ottawa Hospital underwent risk factor-based screening. In the second period (20 months), universal MRSA screening was implemented in which all patients were screened for MRSA upon admission. Results: The regression analysis demonstrated that the universal MRSA screening intervention was not effective in reducing the number of nosocomial MRSA cases. The economic analysis estimated that the universal MRSA screening intervention incurred an additional cost of $1.16 million/year with an estimated additional cost per patient screened of $17.76. Conclusions: The universal MRSA screening intervention was not clinically or economically effective. Further research is required to verify/dispute these findings in other settings.

Lipid homeostasis is an essential factor for proper function both at the level of a cell and of an organism. Dysregulation of this process is responsible for some of the major health concerns of our societies such as obesity and atherosclerosis. Considering the wide variety of lipids and the high dynamic of the system, it is clear that regulation is required to keep the appropriate balance between the different lipids. Although a few regulation pathways are already characterized, some others still wait to be discovered. In order to unravel new players involved in lipid regulation, a screening procedure was developed combining RNA interference in Hela cells and thin layer chromatography. Thereby, it is possible to monitor modifications of lipid composition resulting from siRNA knock-down. Furthermore, the potential of mass spectrometry as a lipid analysis tool in large-scale studies was evaluated. This method was then applied to an essential family of regulatory proteins, the kinases. Lipid composition of 600 kinases knock-downs was analyzed. Mostly, variations in triglyceride and cholesterol levels were observed, suggesting that these lipids are more subject to variation in the cells. Unfortunately, it appears that the screen suffered from a high-rate of off-targets effects, implying that most of the phenotypes observed can’t reliably be linked to the corresponding kinase knock-downs. However, several interesting conclusions can still be derived from this screen. First, it was observed that several siRNA induce a decrease in cholesterol, which is coupled to accumulation of a new lipid. Several lines of evidence suggest that this new lipid is in fact a methylated sterol precursor such as lanosterol or demethyllanosterol. Previously, HMG-CoA reductase was considered as the rate-limiting enzyme of cholesterol biosynthesis and the major regulated step of this process. These data show that another major regulation step occurs more downstream in the pathway at the level of methylated cholesterol precursors. Furthermore, MAPK9 was identified as a new regulator of triglyceride homeostasis at the cellular level. Upon MAPK9 knock-down, an increase in triglyceride content was observed both by thin layer chromatography and mass spectrometry. Accordingly, these cells present an increase in lipid droplets, the cellular organelles responsible for triglyceride storage. Sty1 was also identified as the functional homolog of MAPK9 in S. pombe for this process, as similar increase in triglyceride and lipid droplets is observed in a deletion strain for this gene. Although more detailed studies will be necessary to unravel the molecular mechanism of this process, these data suggest the evolutionary conserved implication of the MAP kinase pathway in the regulation of lipid storage both in humans and in yeasts.

Bakgrund: Enterohemorragisk Escherichia coli (EHEC) är en toxinproducerande bakterie somkan orsaka sporadiska fall av infektion men även ge upphov till allvarliga utbrott. Sjukdomen kan ge symtom alltifrån okomplicerad diarré, blodig diarrétill mycket allvarliga symtomsom hemolytiskt uremiskt syndrom (HUS). De flesta EHEC-falli Sverige förekommer i åldersgruppen ett till fyra år. Syfte: Studienssyfte var att undersöka värdet av en EHEC-screening hos barn under tio år genom att kartlägga förekomst av EHEC och distribution av serotypoch stx-typer. Ytterligare ett syfte var att undersöka om den kliniska bilden är beroende av serotyp och stx-typ. Därutöver undersöktes hur länge man utsöndrars tx i avföringen. Metod: I studien ingick alla barn under tio års ålder, som lämnat avföringsprov under perioden 1 maj 2003 till 30 april 2013i Jönköpingslän. Barnen delades in i de med klinisk EHEC frågeställning och de resterande som ingick i screeningen. Barnen följdes med upprepad provtagning varje vecka efter första positiva provet. Kliniska data samlades in via ett frågeformulär samt via granskning av journaler. Resultat: Totalt diagnostiserades 191 barn (87 flickor och 104 pojkar) med EHEC, av dessa var 162 indexfall och 29 hittades vid smittspårning. Prevalensen av EHEC var 1,8% i gruppen med klinisk frågeställning och 1,5% ingick i screening (p=0,5). Mediantiden för utsöndringav stx i avföringen var 20 dagar (1-256 dagar). Barnmed Stx2 producerande EHEC hade allvarligare symtom. Sju barn insjuknade i HUS, alla var smittade i Sverige. Det var vanligare med Stx2 hos barn smittade i Sverige. I fem av fallen kunde smittkällan fastställas. Konklusion: Studienvisar en lika högprevalens av EHEC i den screenade gruppen som i gruppen där EHEC var efterfrågat. Även svårighetsgraden av symtom var lika i båda grupperna.EHEC-förekomstenvar hög och de flestavarejav serotyp O157. Serotypoberoende metoder vid diagnostikär därför viktiga. Den långa utsöndringstiden utgör en risk för smittspridning. De flesta barnen med Stx2 var smittade i Sverige, vilket medför ökad risk för svår sjukdom. Studiens resultatbekräftar värdet av EHEC-screening hos barn. / Background:Enterohemorrhagic Escherichia coli(EHEC) is a toxin-producing bacterium responsible for sporadic cases of infection as well as serious outbreaks. Symptoms rangefrom uncomplicated or bloody diarrhea to hemolytic uremic syndrome (HUS). In Sweden, most EHEC casesoccurin 1-4-year-old children. Aims:This study aimed at investigate the value of EHEC screening in children younger than 10 years of age by evaluatingthe prevalence of EHEC and the distribution of serotypes and stxtypes. We also aimed t ocorrelate clinical symptoms with EHEC serotypes and stxtypes. Furthermore the duration of faecal shedding of stxwas investigated. Methods: The study examined stool samples collected fromall children younger than 10 years of age between1 May 2003 and April 2013 in the County of Jönköping. We divided the children into a physician-requested EHEC analysis group and ascreening group. Children who tested positive for stxwere sampled weekly after initial EHEC diagnosis. We used a questionnaire and reviewed medical records to collect clinical data. Results: Among 191 children (87 girls and 104 boys) with confirmed EHEC, 162 specimens were index cases and 29 were found by contact tracing. The EHEC prevalence was 1.8 % in the EHEC requested group and 1.5 % in the screening group (p=0.5). The median duration of stxdetection in faeces was 20 days (1-256 days). Symptoms were more severe in children with Stx2-producing EHEC, and seven children developed HUS, all infected in Sweden. We were able to determine the source of infection in five cases. Conclusions: This study showed that the EHEC prevalence and severity of symptoms where equal between the requested and screening group. HighEHEC prevalence and a high proportion of non-O157 isolates were found. Our results emphasize the need for serotype-independent methods for EHEC detection. The long duration of stxdetection in stools indicates a risk for transmission. Most children with Stx2 were infected in Sweden, suggesting a higher risk forsevere symptoms. Our results confirm the value of EHEC screening in children. / <p>ISBN 978-94-86739-92-8</p>

Statement of the problem: Methicillin-resistant Staphyloccocus aureus (MRSA) is a pathogen of increasing concern and is associated with higher hospital readmission rates, poorer prognosis, and increased mortality resulting in increasing costs to the Canadian healthcare system.1-13 Institutions have been challenged with developing effective infection control programs to prevent the spread of MRSA. The purpose of this thesis was to examine the clinical and cost-effectiveness of a universal MRSA screening intervention within a large tertiary care facility. Methods of investigation: The retrospective population-based observational study consisted of two periods. In the first period (24 months), patients admitted to the Ottawa Hospital underwent risk factor-based screening. In the second period (20 months), universal MRSA screening was implemented in which all patients were screened for MRSA upon admission. Results: The regression analysis demonstrated that the universal MRSA screening intervention was not effective in reducing the number of nosocomial MRSA cases. The economic analysis estimated that the universal MRSA screening intervention incurred an additional cost of $1.16 million/year with an estimated additional cost per patient screened of $17.76. Conclusions: The universal MRSA screening intervention was not clinically or economically effective. Further research is required to verify/dispute these findings in other settings.

Pharmaceuticals are environmental contaminants causing steadily increasing concern due to their high usage, ubiquitous distribution in the aquatic environment, and potential to exert adverse effects on the ecosystems. After being discharged from wastewater treatment plants (WWTPs), pharmaceuticals can undergo transformation processes in surface waters, of which microbial degradation in river sediments is considered highly significant. In spite of a substantial number of studies on the occurrence of pharmaceuticals in aquatic systems, a comprehensive understanding of their environmental fate is still limited. First of all, very few consistent datasets from lab-based experiments to field studies exist to allow for a straightforward comparison of observations. Secondly, data on the identity and occurrence of transformation products (TPs) is insufficient and the relation of the behavior of TPs to that of their parent compounds (PCs) is poorly understood. In this thesis, these knowledge gaps were addressed by integrating the TP identification using suspect/non-target screening approaches and PC/TP fate determination. The overarching objective was to improve the understanding of the fate of pharmaceuticals in rivers, with a specific focus on water-sediment interactions, and formation and behavior of TPs. In paper I, 11 pharmaceutical TPs were identified in water-sediment incubation experiments using non-target screening. Bench-scale flume experiments were conducted in paper II to simultaneously investigate the behavior of PCs and TPs in both water and sediment compartments under more complex and realistic hydraulic conditions. The results illustrate that water-sediment interactions play a significant role for efficient attenuation of PCs, and demonstrate that TPs are formed in sediment and released back to surface water. In paper III the environmental behavior of PCs along stretches of four wastewater-impacted rivers was related to that of their TPs. The attenuation of PCs is highly compound and site specific. The highest attenuation rates of the PCs were observed in the river with the most efficient river water-pore water exchange. This research also indicates that WWTPs can be a major source of TPs to the receiving waters. In paper IV, suspect screening with a case-control concept was applied on water samples collected at both ends of the river stretches, which led to the identification of several key TPs formed along the stretches. The process-oriented strategies applied in this thesis provide a basis for prioritizing and identifying the critical PCs and TPs with respect to environmental relevance in future fate studies. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.</p>

This submitted master's thesis is called "A retrospective view on the neonatal screening". The main aim of this thesis is to map a retrospective view on the neonatal screening in the basis of teoretical fundaments. Thesis deals with theoretical level of problematic. Thesis summarizes the historical development of clinical and laboratory neonatal screening. Next to that there are mentioned procedures executed by a nurse in relation with neonatal screening. Thesis also includes a characteristics of specific illnesses witch can be discovered and then correctly treated. Purpose of this thesis is to broaden a necessary knowledge not only among students and medical staff, but mainly among child nurses witch are performing a blood collections for the neonatal screening and they are in most cases the very first persons to be asked by parents for more informations. Great knowledge of the neonathal screening is elementar for every child nurse. Thesis can also be used as a certain guide for parents which will gain more informations about neonatal screening performed (with parents approval) on their newborn child. This master's thesis have been written after a proper study of available materials and have been summarized to complex text. Scientific analysis, synthesis and explantation were used during work on this thesis. We have used many external sources to create this thesis. Most valuable informations and publications have been found in the internet database PubMed, mostly in english. Very important was research and full text articles provided by the National medical library in Prague. Last but not least were used printed publications in czech and english.

The topic of health is currently very up-to-date and the need for population health promotion and disease prevention is becoming increasingly important. The consequences of neglecting prevention and health promotion on the state's economy are clear, whether it is about increasing public spendings on health care or indirect effects on the level of human capital. The aim of this work is to analyze health promotion in the Czech Republic with a focus on mammographic screening programme introduced in 2002. The study demonstrates a decrease in breast cancer mortality following the screening examination and an increase in the number of tumor findings in earlier stages of the disease. It also analyzes the effect on costs of health care and the impact of screening on them. It also proposes to extend preventive screening examinations to other areas where their implementation could be useful in the future.

Statement of the problem: Methicillin-resistant Staphyloccocus aureus (MRSA) is a pathogen of increasing concern and is associated with higher hospital readmission rates, poorer prognosis, and increased mortality resulting in increasing costs to the Canadian healthcare system.1-13 Institutions have been challenged with developing effective infection control programs to prevent the spread of MRSA. The purpose of this thesis was to examine the clinical and cost-effectiveness of a universal MRSA screening intervention within a large tertiary care facility. Methods of investigation: The retrospective population-based observational study consisted of two periods. In the first period (24 months), patients admitted to the Ottawa Hospital underwent risk factor-based screening. In the second period (20 months), universal MRSA screening was implemented in which all patients were screened for MRSA upon admission. Results: The regression analysis demonstrated that the universal MRSA screening intervention was not effective in reducing the number of nosocomial MRSA cases. The economic analysis estimated that the universal MRSA screening intervention incurred an additional cost of $1.16 million/year with an estimated additional cost per patient screened of $17.76. Conclusions: The universal MRSA screening intervention was not clinically or economically effective. Further research is required to verify/dispute these findings in other settings.

Breast cancer is the most common nonskin cancer diagnosed among women in the United States and throughout the world, and the leading cause of cancer deaths. Screening recommendations and guidelines vary depending on the organization. Screening modalities include self breast examination, clinical breast examination, mammography, ultrasound, and magnetic resonance imaging. Screening guidelines vary based on individual risk assessment and age.