Background: Survival analysis is sometimes called time-to-event analysis. The Cox model is used widely in survival analysis, where the covariates act multiplicatively on unknown baseline hazards. However, the Cox model requires the proportionality assumption, which limits its applications. The additive hazards model has been used as an alternative to the Cox model, where the covariates act additively on unknown baseline hazards. Objectives and methods: In this thesis, performance of the Cox multiplicative hazards model and the additive hazards model have been demonstrated and applied to the transfer, lifting and repositioning (TLR) injury prevention study. The TLR injury prevention study was a retrospective, pre-post intervention study that utilized a non-randomized control group. There were 1,467 healthcare workers from six hospitals in Saskatchewan, Canada who were injured from January 1, 1999 to December 1, 2006. De-identified data sets were received from the Saskatoon Health Region and Regina Quappelle Health Region. Time to repeated TLR injury was considered as the outcome variable. The models goodness of fit was also assessed. Results: Of a total of 1,467 individuals, 149 (56.7%) in the control group and 114 (43.3%) in the intervention group had repeated injuries during the study period. Nurses and nursing aides had the highest repeated TLR injuries (84.8%) among occupations. Back, neck and shoulders were the most common body parts injured (74.9%). These covariates were significant in both Cox multiplicative and additive hazards models. The intervention group had 27% fewer repeated injuries than the control group in the multiplicative hazards model (HR= 0.63; 95% CI=0.48-0.82; p-value=0.0002). In the additive model, the hazard difference between the intervention and the control groups was 0.002. Conclusion: Both multiplicative and additive hazards models showed similar results, indicating that the TLR injury prevention intervention was effective in reducing repeated injuries. The additive hazards model is not widely used, but the coefficient of the covariates is easy to interpret in an additive manner. The additive hazards model should be considered when the proportionality assumption of the Cox model is doubtful.

Background: Survival analysis is sometimes called time-to-event analysis. The Cox model is used widely in survival analysis, where the covariates act multiplicatively on unknown baseline hazards. However, the Cox model requires the proportionality assumption, which limits its applications. The additive hazards model has been used as an alternative to the Cox model, where the covariates act additively on unknown baseline hazards. Objectives and methods: In this thesis, performance of the Cox multiplicative hazards model and the additive hazards model have been demonstrated and applied to the transfer, lifting and repositioning (TLR) injury prevention study. The TLR injury prevention study was a retrospective, pre-post intervention study that utilized a non-randomized control group. There were 1,467 healthcare workers from six hospitals in Saskatchewan, Canada who were injured from January 1, 1999 to December 1, 2006. De-identified data sets were received from the Saskatoon Health Region and Regina Quappelle Health Region. Time to repeated TLR injury was considered as the outcome variable. The models goodness of fit was also assessed. Results: Of a total of 1,467 individuals, 149 (56.7%) in the control group and 114 (43.3%) in the intervention group had repeated injuries during the study period. Nurses and nursing aides had the highest repeated TLR injuries (84.8%) among occupations. Back, neck and shoulders were the most common body parts injured (74.9%). These covariates were significant in both Cox multiplicative and additive hazards models. The intervention group had 27% fewer repeated injuries than the control group in the multiplicative hazards model (HR= 0.63; 95% CI=0.48-0.82; p-value=0.0002). In the additive model, the hazard difference between the intervention and the control groups was 0.002. Conclusion: Both multiplicative and additive hazards models showed similar results, indicating that the TLR injury prevention intervention was effective in reducing repeated injuries. The additive hazards model is not widely used, but the coefficient of the covariates is easy to interpret in an additive manner. The additive hazards model should be considered when the proportionality assumption of the Cox model is doubtful.

The main objective of this study is to divide a number of colorectal cancer cases into subgroups based on their molecular features using cluster analysis. The data used is supplied by a research group at Pathology, the Department of Medical Biosciences, Umeå University, and consists, after some preparation, of 455 observations which is a larger data set than many similar studies. The molecular variables that the clustering is based on are CIMP (CpG Island Methylator Phenotype), MSI (Micro Satellite Instability), BRAF- and KRAS-mutations. These are categorical variables and consequently the clustering method used is PAM (Partitioning Around Medoids) which is particularly useful with data on diverse variable level. The final analysis results in four subgroups that are represented by different combinations of attributes on the aforementioned variables. The disparity between the clusters are then evaluated by, for instance, comparing the survival time for their pertaining patients and it appears that two of the clusters are significantly different in this aspect. Other patient related and tumor specific characteristics are also linked with the separate cancer types and tested if they occur in varying extent. The locations of the tumors in the colon are for instance significantly different between the groups. Cluster analyses are exploratory tools so the choice of useful variables and subsequent interpretation of the results can be complicated and require relevant subject knowledge. / Huvudsyftet med denna studie är att med hjälp av klusteranalys dela in en mängd tjocktarmscancerfall i undergrupper baserat på deras molekylära egenskaper. Materialet som används tillhandahålls av en forskningsgrupp vid Patologi, Institutionen för medicinsk biovetenskap, Umeå universitet, och består efter viss bearbetning av 455 observationer vilket är en större datamängd än flera liknande studier. De molekylära variabler som ligger till grund för klusterindelningen är nivån på CIMP (CpG Island Methylator Phenotype), MSI (Mikrosatellitinstabillitet), BRAF- och KRAS-mutationer. Dessa är kategoriska variabler och därför används PAM (Partitioning Around Medoids) som är en särskild klusterteknik lämpad vid data på varierade variabelnivåer. I det slutliga resultatet fås fyra undergrupper som representeras av olika kombinationer av utfallen på ovannämnda variabler. Klustren utvärderas bland annat genom att jämföra överlevnadstiden för varje kluster, och det visar sig att två av klustren skiljer sig signifikant åt i detta avseende. Även andra patientrelaterade och tumörspecifika egenskaper kopplas samman till de olika cancertyperna och testas om de förekommer i varierande utsträckning. Var någonstans tumören är placerad är till exempel signifikant skilt mellan grupperna. Klusteranalyser är explorativa redskap så valet av variabler och sedermera tolkningar av resultat kan vara komplicerade och kräva stor sakkunskap.

Yes / Failure of systemic cancer treatment can be, at least in part, due to the drug not being delivered to the tumour at sufficiently high concentration and/or sufficiently homogeneous distribution; this is termed as “pharmacokinetic drug resistance”. To understand whether a drug is being adequately delivered to the tumour, “precision pharmacology” techniques are needed. Mass spectrometry imaging (MSI) is a relatively new and complex technique that allows imaging of drug distribution within tissues. In this review we address the applicability of MSI to the study of cancer drug distribution from the bench to the bedside. We address: (i) the role of MSI in pre-clinical studies to characterize anti-cancer drug distribution within the body and the tumour, (ii) the application of MSI in pre-clinical studies to define optimal drug dose or schedule, combinations or new drug delivery systems, and finally (iii) the emerging role of MSI in clinical research. / Spanish Medical Oncology Society (SEOM) for contribution with a grant for research abroad of Dr. Jove, “Instituto Carlos III” for contribution with a “Río Hortega” Grant (nº CM17/00008) for Dr. Jove

No description available.

In the everyday environment, we receive information from various sensory inputs, and yet, we perceive and integrate the incoming information in a way that is meaningful. Remarkably, infants and toddlers are capable of sensory integration early in life. By integrating information, particularly speech, infants ultimately learn to reproduce language by late toddlerhood. These language skills form a foundation for learning and achievement later in life, and there is documented evidence that language skills vary by experiences related to socioeconomic status (SES). Language disparities can be measured early in development, and continue to divide throughout childhood. Although there is clear evidence that language learning trajectories are influenced by SES, less is known about multisensory integration (MSI) as they are measured here and how these skills may differ as a function of SES. Here, MSI was investigated to gain insight into the potential changes that occur in MSI and expressive vocabulary for 68 toddlers between 18 months and 24-months. Finally, this relationship was investigated in the context of SES. At 18-months, toddlers demonstrated significant matching for nonsocial conditions, and at 24-months toddlers also matched for low competition social trials, thus demonstrating an improvement in matching from 18 to 24-months. There were no significant relationships between MSI and expressive vocabulary, and only one unexpected relationship between MSI and SES. These findings extend the research from Bahrick and colleagues (2018) by supplementing the previously studied 12-month-olds and 2-5-year-olds with an earlier age (e.g., 18-months), and open new doors for studying toddlers’ emerging social MSI. / M.S. / In the everyday environment, we experience various sights and sounds from multiple sources, and yet, we perceive the incoming information in a way that is meaningful. Infants and toddlers are also capable of combining multiple sources of information together in a way that is beneficial for language learning. Merging sensory information (e.g., correctly matching their mother’s voice to their mother) creates a foundation for language learning. There is evidence that suggests language abilities differ as a result of socioeconomic status (SES), and can be found early in development and continue to progress into childhood. Although research indicates differences in language arise as a result of SES, it is unclear whether the ability to merge multiple sources of information (also known as multisensory integration), particularly while experiencing competing information (e.g., noise, multiple speakers) also differs as a result of SES. Here, the ability to integrate multiple sources of information and vocabulary in young toddlers ages 18-months and 24-months was studied to understand whether these skills progress with age and also whether they differ as a result of SES. 18-month-olds demonstrated better integration of sensory information when blocks were falling (e.g., nonsocial event) than when women were shown on the screen speaking in child-directed speech (e.g., social event). At 24- months, toddlers also correctly matched the information of the social event when there was no competing information on the screen, thus improving social integration from 18-months. There were no significant relationships between MSI and vocabulary, and only one relationship between MSI and SES. More research will need to be conducted to understand the improvement of social integration from 18 to 24-months, and more questions will need to be addressed on how SES may play a role in integrating information.

Le phénomène dit de domestication moléculaire qui a été rapporté pour certains transposons à ADN a abouti à la formation de néogènes qui codent des protéines potentiellement impliquées dans la stabilité du génome de part une activité recombinase. L’objectif de ce travail est d’étudier l’expression de 23 recombinases néogéniques d’intérêt dérivées de transpsons à ADN dans une série de cancers colorectaux. Nous avons fabriqué de nouveaux anticorps performants pour l’étude en western blot et en immunofluorescence de l’expression du gène SETMAR qui code pour la protéine Metnase dans des lignées cancéreuse différentes et dans des tissus du côlon tumoraux et normaux. Nos résultats démontrent que la vaccination d’ADN avec la formulation utilisée est une méthode qui donne de meilleurs résultats que l'injection de peptide ou protéines purifiées. Nous avons observé une expression de la protéine metnase dans des lignées cancéreuses de cancer du côlon, de leucémie et de cancer du sein. Le niveau d’expression de cette protéine Metnase dans le cancer du côlon semble être associé au statut MSI ce qui suggère un rôle de cette protéine dans les mécanismes de carcinogenèse et de progression tumorale. / During a phenomena known as molecular domestication has been reported for some DNA transposons leading to the formation of Neogenes which encode proteins potentially involved in the genome stability. The objective of this work is to study the expression of 23 neogenic recombinases of interest derived from DNA transpsons in a series of frozen colorectal cancers. We have manufactured new effective antibodies for the study of the expression of SETMAR gene which encode Metnase protein in different cancer cell lines and tissues of colon tumoral and normal by the method of Western blot and immunofluorescence. Our results demonstrate that DNA vaccination with the formulation used here is a method that gives better results than the injection of peptide or purified proteins. We observed an expression of Metnase protein in cell lines of colorectal cancer, leukemia and breast cancer. The level of expression of the Metnase protein in colon cancer appears to be associated to the MSI status which suggests a role for this protein in the mechanisms of carcinogenesis and tumor progression.

No description available.

This work concerns about designing of communication protocol for generic processor simulator. The main objective of this work was to design a communication protocol which allows to simulate multiprocessor system on a cluster of computers.

<p>Denna rapport beskriver Windows Installer och hur dess API kan användas för att generera MSI-paket. Det förklaras hur MSI-paket bör vara utformade och hur dessa kan användas.</p><p>Projektet resulterade i en prototyp åt uppdragsgivaren Capitex AB. Prototypen kunde användas för att generera MSI-paket för applikationen Säljstöd.</p>