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Coming dissertations at MedFak

  • Homicide Injury Quantification : Measures of injury severity in homicide victims and associations with homicide characteristics Author: Fredrik Tamsen Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-383637 Publication date: 2019-06-03 13:12

    Some previous studies have found that the amount and severity of injuries in homicide victims correlate with different homicide characteristics, such as the victim-offender relationship and drug influence of the offender. If such relationships exist, they may be used by homicide investigators as part of an offender profiling.

    Furthermore, injury severity may be helpful in understanding the nature of lethal violence. If the injuries change over time or differ between regions, this may say something about the underlying causes and thus help society to take preventive measures. However, measures of injury severity are often missing in homicide epidemiology. This may in part be due to a lack of standardized and accessible ways to quantify injuries in homicide victim.

    To address these issues, there is a need for methods to quantify injury severity in homicide victims. The aim of the current thesis was to investigate different types of injury measures and their applicability to homicide victims. The aim was also to use such measures to address research questions related to offender profiling.

    Starting off with injury scores used in trauma research and two scores developed specifically for homicide victims, these measures were applied to a general homicide population. Since there is no obvious “gold standard” for injury severity quantification on homicide victims, one had to be defined to validate the applied methods. Out of forensic experience and rational reasoning, the Sum of all AIS scores (SAIS) was proposed as a reference measure. The other scores were then evaluated through their correlations with the SAIS.

    In the following study, the injury severity in homicides from different time periods was measured. There were statistically significant increases over time with respect to excessive injuries and the number of lethal injuries per victim. These changes can reflect both a brutalization of homicidal violence, improved trauma care, or shifts in the methods by which people are killed.

    Next, the associations between injury severity and homicide characteristics were analysed. No relevant associations between injury severity and victim-offender relationship were found. Neither were there any connections between benzodiazepine influence in the offender and injury severity on the victim. Thus, the studies do not support the use of injury severity scores for offender profiling in a general homicide population.

  • Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease Author: Anas Kh. Al-Saffar Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382486 Publication date: 2019-05-23 14:07

    Synchronized motility, permeability and secretory (hormones and enzymes) events are integral to normal physiology. Smooth muscle syncytium operates with enteric nervous system (ENS) and endocrine signalling to accommodate, mix and control passage of ingested materials. The intestinal epithelial cells (IECs) drive digestion and absorption while repelling harmful compounds.

    This thesis investigated GI barrier function (permeability, mucosal integrity), motility and hormonal patterns in inflammatory bowel disease (IBD) by: 1) assessing GI motility using a wireless motility capsule (WMC, SmartPill®) and video capsule endoscopy (VCE, Pillcam®), 2) investigation of intestinal fatty acid binding protein (I-FABP) as a biomarker of Crohn’s disease (CD) disease activity, 3) evaluation of small intestinal permeability in IBD, 4) investigating meal-related WMC motility and simultaneous hormonal (e.g., Ghrelin, GLP-1, GIP, PYY) patterns in IBD. Reference WMC motility values for transit times for gastric emptying, small bowel, orocecal, small+large bowel, colon and whole gut were established. Software-generated estimates and visually determined values were nearly identical. Compared with VCE estimates (represents fasting conditions), the WMC records longer GET and SBTT. Variations in intra-subject reproducibility must be considered in clinical investigations. This data was then used to investigate IBD patients. I-FABP was primarily expressed in the epithelium of the small bowel and to lesser extent also in the colon and stomach. Circulating I-FABP was elevated in active CD with a magnitude comparable to TNFα. I-FABP lowers and rises again in parallel with TNFα and HBI during infliximab treatment. I-FABP can be used as a jejunum and ileum selective prognostic biomarker for monitoring disease activity. Increased small intestine mucosal barrier permeability to lactulose in both CD and UC was found. Sucralose can serve a dual purpose in quantifying small and large intestinal permeability. Small intestinal hyper-permeability was not revealed as a transporter dependent nutrient (riboflavin) malabsorption. Using the WMC, consistent motility disturbances in IBD were limited, as were differences in pH. However, disturbances within many individuals were found. As part of the investigation, defects in gut peptide and metabolic hormone meal responses were found, typically higher plasma levels. No clear associations between hormones and motility were found. Effects on hunger/satiety signaling in IBD are anticipated.

    The present thesis shows the utility of the WMC and gut barrier tests in monitoring IBD patients.

  • Precise cell manipulations and imaging of cellular responses : Methods developed using microfluidic, 3D-printing and microfabrication technologies Author: Nikos Fatsis-Kavalopoulos Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382277 Publication date: 2019-05-22 10:29

    It is at the heart of biological and medical research to try and understand how cells communicate with each other, and how cells respond to alterations in their environment, including treatment with different drugs. There is in this context a continued need for better methods that allow researchers to precisely manipulate cells and their microenvironment and to study the resulting responses using high-resolution live microscopy. This thesis presents the development and implementation of several devices that addresses these needs.

    A novel microfluidic device called the cell assembly generator (CAGE) was created to generate precisely composed cell clusters of different cell types; the first of its kind. Experimental evidence demonstrated that the CAGE chip can be used to study paracrine signalling in tailor-made cancer cell clusters composed of up to five cells.

    A high-throughput microfluidic chip for rapid phenotypic antibiotic susceptibility testing was developed and tested using 21 clinical isolates of Klebsiella pneumoniae, Staphylococcus aureus and Escherichia coli against a panel of antibiotics. Stable minimum inhibitory concentration values were obtained from this system within 2-4 hours with high accuracy to the standard method.

    3D-printing was used to create a modular and affordable time-lapse imaging and incubation system, called ATLIS. This system enables researchers to convert simple inverted microscopes into live cell imaging systems, where images and movies of living cells can be recorded using a regular smartphone.

    Finally, a strategy was developed for the generation of modular microfluidic systems using 3D-printed moulds for PDMS casting, to enable studies of leukocyte adherence to differentially treated endothelial cell populations in the same field of view and under the same conditions.

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