Optimization of biologic therapy in children with inflammatory bowel disease (IBD) using modern biomarkers Abstract to thesis Study programme: Biochemistry and Pathobiochemistry Introduction: In adults, infliximab (IFX) levels correlate with disease activity and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in paediatric population. Methods: This study was performed as a prospective observational study. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). We used multivariate analysis to identify the predictors of IFX levels. IFX and ATIs levels were meassured using ELISA. Results: Lower levels of IFX were associated with ATIs positivity (OR [odds ratio] 0.027, CI [confidence interval] 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and CPT levels were found in patients with lower IFX levels. The optimal combination of specificity (50%) and sensitivity (74%) for disease activity was calculated for IFX levels ≥ 1.1 µg/ml using CRP level < 5 mg/l as a marker of laboratory remission. In a model that used CPT ≤...

In Introduction, the author of this dissertation deals with postoperative venous thromboembolism (VTE), hereditary and acquired risk factors, prophylaxis regimens and recent recommendation of VTE prevention in surgery. In Practical part of this work the author assesses the risk of VTE in surgical patients according to risk assessment model. Genetic testing is carried out in all patients to determine the incidence of hereditary thrombophilia and coagulation markers are measured in 28-days postoperative period. Prevalence of VTE in 1-year postoperative period is observed. The results are analysed in group of patients with benign disease (hernia and gallstone disease) and group of patients with malignancy (colorectal cancer and pancreatic cancer) separately. The objective of this work is to determine the incidence of the most frequent thrombophilic mutations (factor V Leiden mutation and protrombin G20210A mutation) and assess the impact of hereditary thrombophilia on incidence of postoperative venous thromboembolism in general surgery. Validation of venous thrombosis risk assessment model recommended by Czech Society for Thrombosis and Hemostasis is further objective.

The purpose of this project was to investigate a cylindrical cavity resonator and use microwaves to heat up a material in the cavity. This was done by measuring the Q-factor and the resonance frequency of the cavity, both with and without material inside. The chosen material was graphite, and more accurate measurements were done with that specific material. A program called QZero was used to export the Q-factor and the resonance frequency from the measurement data received from a VNA and the program also gave error estimations. Then electromagnetic simulations were done using Comsol. Both an empty cavity and a cavity where graphite has been inserted were simulated and the results were compared to the actual measurements. To measure temperatures inside the cavity, a pyrometer was to be used. The cavity resonator has small circular holes through the side, and a frame was designed and produced using a 3D-printer in order to lock the pyrometer in place in front of one of the holes. A power supply was also installed to the pyrometer. In order to send microwaves into the cavity, a signal generator was used. It was connected to an amplifier and the amplification as well as the efficiency was noted. The pyrometer could only measure temperatures above 490 $\degree$C. This was not achieved, so a handheld electrical thermometer was used. The temperature of the graphite was measured and then compared to how hot the graphite would be without heat loss. For the empty cavity, a Q-factor of 3200 for the resonance frequency of around 2.4 GHz was measured, which matched the simulated measurements in Comsol. When graphite was inserted to the cavity, the Q-factor lowered to 300 in the real experiment. A discrepancy was found between the actual measurements, and the Comsol simulations in which the graphite only lowered the Q-factor to 2570. The reason for this is believed to be either with an error to how the material was chosen in Comsol, since there were many types of graphite to select with many settings to change. Another reason could be an error with the setup itself due to the sheer complexity of the program. / Syftet med detta projekt är att undersöka en cylindrisk kavitet samt att använda mikrovågor för att värma upp ett material i kaviteten. Detta gjordes genom att mäta kavitetens Q-faktor och resonansfrekvens med och utan material. Sedan valdes grafit ut som det materialet som skulle testas och mer noggranna mätningar gjordes på just det materialet, och programmet QZero användes för att få ut mer noggrann data samt gav en felmarginal på Q-faktorn. Efter det gjordes simuleringar i programmet Comsol av kaviteten med och utan grafit och jämfördes med de faktiska värdena. För att mäta temperatur av materialet i kaviteten designades en hållare som en pyrometer skulle fästas vid och riktas mot materialet i kaviteten. Även en strömförsörjning till pyrometern installerades. För att skicka in mikrovågor i kaviteten användes en signalgenerator som var kopplad till en förstärkare. Förstärkningen mättes och förstärkarens effekt noterades. I slutändan nåddes inte de temperaturer som krävdes för pyrometern, så en elektrisk termometer användes för att mäta temperaturen på grafiten och detta jämfördes sedan mot den energin som absorberades av grafiten, då energin tillförd till grafiten och grafitens specifika värmekapacitet var känt. Prestandan av experimentuppställningen undersöktes också. For den tomma kaviteten mättes en Q-faktor på 3200 och resonansfrekvensen var 2.4 GHz. Detta stämde bra överens med simuleringarna i Comsol. När grafit fördes in i kaviteten sänktes Q-faktorn till 300. En avvikelse upptäcktes mellan de faktiska mätningarna och simuleringarna. I simuleringen sänktes Q-faktorn bara till 2570, en andledning till detta tros vara antingen vara hur materialet valdes, då det fanns olika typer av grafit med olika inställningar att välja mellan i Comsol. En annan felkälla kan vara något fel med uppställningen på grund af hur avancerat Comsol var. I värmeexperimentet hade förstärkaren en låg verkningsgrad vilket ledde till överhettning om för stor effekt användes. Experimentet begränsades därför till att använda upp till två watt. Vid exponerig under 30 sekunder värmdes grafiten upp till 100-150$\degree$C, vilket var avsevärt lägre än den teoretiska uppvärmingen till 1700$\degree$ beräknad från energin tillförd till grafiten. Antagandet är att temperaturen hamnade i ett jämnviktsläge kring 100-200$\degree$C eller att resonansfrekvensen ändrades vilket ledde till en minskning av energi tillförd till grafiten.

ATP synthase represents the key enzyme of cellular energy provision and ATP synthase disorders belong to the most deleterious mitochondrial diseases affecting pediatric population. The aim of this thesis was to identify nuclear genetic defects and describe the pathogenic mechanism of altered biosynthesis of ATP synthase that leads to isolated deficiency of this enzyme manifesting as an early onset mitochondrial encephalo-cardiomyopathy. Studies in the group of 25 patients enabled identification of two new disease-causing nuclear genes responsible for ATP synthase deficiency. The first affected gene was TMEM70 that encodes an unknown mitochondrial protein. This protein was identified as a novel assembly factor of ATP synthase, first one specific for higher eukaryotes. TMEM70 protein of 21 kDa is located in mitochondrial inner membrane and it is absent in patient tissues. TMEM70 mutation was found in 23 patients and turned to be the most frequent cause of ATP synthase deficiency. Cell culture studies also revealed that enzyme defect leads to compensatory-adaptive upregulation of respiratory chain complexes III and IV due to posttranscriptional events. The second affected gene was ATP5E that encodes small structural epsilon subunit of ATP synthase. Replacement of conserved Tyr12 with Cys caused...

Mantle cell lymphoma (MCL) is a subtype of B-non-Hodgkin's lymphoma, characterized by often relapses. Despite an Ibrutinib (a Bruton's kinase inhibitor) implementation into salvage therapy, these patients often relapse with biologically highly aggressive disease and very poor prognosis. An increased activation of alternative metabolic pathways was described as one of ibrutinib-resistance mechanisms. Some of these pathways have also significant proangiogenic activity (e.g. PI3K-AKT-mTOR). In presented study, we established and standardized a real-time ultrasound and photoacoustic imaging of neovascularization and tissue oxygenation of subcutaneous MCL tumors in mice. Ultrasound and photoacoustic imaging is a fast, non-invasive method for angiogenesis evaluation in subcutaneous tumors with huge preclinical potential. Using MCL mice models, we also demonstrated the importance of CD31/PECAM-1 expression for engraftment, growth and spread of MCL cells in vivo. The level of CD31 expression in primary MCL cell (obtained directly from MCL patients) positively correlates with extent of extranodal involvement. CD31 facilitates survival and regulates extranodal spread of mantle cell lymphoma. We found that increased VEGFA expression causes not only increased microvessel density due to higher sprouting...

Bauteile mit Rissen können mit Hilfe der Bruchmechanik bewertet werden. Da die Ermittlung der Rissspitzenbeanspruchung nicht immer analytisch gelingt, ist die Nutzung numerischer Verfahren von Vorteil. Nach einer kurzen Einführung in die Bruchmechanik wird an zwei Beispielen die Vorgehensweise diskutiert.

Hematopoietic stem cells (HSCs) have historically been difficult to maintain ex vivo with many attempts to culture them in vitro by mimicking their natural biological environment. Providing a hypoxic environment is one way to achieve this goal and can be performed by using hypoxia stimulating compounds that inhibits the degradation of HIF1a which plays an important role in regulating hypoxia. For each sample 50 murine HSCs were isolated with fluorescence-activated cell sorting (FACS) and cultured with different concentrations of the hypoxia inducible compound Adaptaquin for 13 days followed by analysing with flow cytometry. The results showed an increase in proliferation of treated cells with the highest average total viable cell count for cells treated with 100 nM Adaptaquin of 4,70 ± 1,12 x 105 cells compared to the control which had 2,39 ± 0,76 x 105 cells. The HSC frequency was highest in the control samples with an average of 1,91 ± 0,42 % compared to the 5 mM treated samples with the highest average HSC frequency which was 1,52 ± 0,82 %. The biggest noticeable difference between the control and treated samples was seen when observing the total cell count. The difference in proliferation was on the other hand too small to see significant difference between the samples. The conclusion is that Adaptaquin did not have any significant impact on keeping the cells undifferentiated but could have a potential to be used as a compliment to other factors to maintain HSCs in vitro and to mimic its hypoxic biological environment. / Hematopoetiska stamceller (HSCs) har historiskt sett varit svåra att odla ex vivo och många försök har genomförts in vitro genom att efterlikna deras naturliga biologiska miljö. Att tillhandahålla en hypoxisk miljö är en metod för att uppnå detta och kan göras med användning hypoxi-stimulerande substanser som hämmar nedbrytningen av HIF1a som spelar en viktig roll i regleringen av hypoxi. För varje prov isolerades 50 murina HSCs med fluorescence-activated cell sorting (FACS) och odlades med olika koncentrationer av det hypoxi-inducerande ämnet Adaptaquin under 13 dagar följt av analys med flödescytometri. Resultaten visade en ökning i avseende på proliferationen hos behandlade celler där det högsta genomsnittliga totala antalet levande celler behandlade med 100 nM Adaptaquin som var 4,70 ± 1,12 x 105 celler jämfört med kontrollen som hade 2,39 ± 0,76 x 105 celler. HSC-frekvensen var högst i kontrollproverna med ett genomsnitt på 1,91 ± 0,42 % jämfört med proverna behandlade med 5 mM Adaptaquin som hade den högsta genomsnittliga HSC-frekvensen som låg på 1,52 ± 0,82 %. Den största synliga skillnaden mellan kontroll- och behandlingsprover var synlig när det observerade totala antalet celler jämfördes mellan behandlade prover som i genomsnitt hade fler totala celler. Skillnaden i proliferation var å andra sidan för liten för att se en signifikant skillnad mellan proverna. Slutsatsen är att Adaptaquin inte hade någon signifikant påverkan på att hålla HSCs odifferentierade men kan ha potential att användas som ett komplement till andra faktorer för att odla HSCs in vitro och efterlikna dess hypoxiska biologiska miljö.

Sjöfarten har förändrats genom tiderna och fartygen har utrustats med avancerad teknologi. Trots högutbildade operatörer och högteknologiska fartyg så inträffar allvarliga sjöolyckor som kan härledas till mänskliga fel och teknologiska brister. Syftet med studien är att utreda hur digitalisering ombord på fartyg påverkar sjösäkerheten. Metoden som används för att utreda digitaliseringens effekter är en systematisk kvalitativ litteraturstudie. Väl avvägda sökord och strukturerad utsortering av artiklar summeras i totalt tjugotvå inkluderade och analyserade artiklar. De studerade artiklarnas innehåll tematiseras och presenteras i studiens resultat indelat i fyra huvudteman respektive fyra underteman. Studiens resultat visar att digitalisering kan leda till effektivisering, kostnadsbesparingar och miljövinster. Digital teknologi har potential att underlätta beslutsfattandet för sjöbefäl och arbetet med navigation kan underlättas med autonoma inslag. En ökad andel autonoma inslag kan dock leda till att sjöbefälets kunskaper går förlorade. Även om digital teknologi är driftsäker så är den skapad av människan vilket kan betyda att tekniken påverkats av den mänskliga faktorn. Digital teknologi fattar beslut på ett förprogrammerat sätt och har svårt att göra helhetsbedömningar i komplexa situationer. Obemannade fartyg kan bli verklighet och sjöbefälet arbetsuppgifter kan förändras. På grund av teknologins avsaknad av mänskligt sunt förnuft så kan sjöbefälen bidra till sjösäkerheten. I framtiden kan nya krav ställas på sjöbefäl och kunskaper om avancerad teknik, autonoma system och förmågan att avhjälpa fel som uppstår i tekniken. För att rusta sjöbefälen kan flexibla utbildningssystem bidra till att förbereda sjöbefälen för yrkeslivet. Den maritima industrins anpassning mot digitalisering kan underlättas genom samverkan mellan regulatoriska myndigheter, organisationer och människor. / The shipping industry has experienced changes over time and modern ships are equipped with advanced technology. Despite highly trained operators and technological ships, serious maritime accidents occur which can be traced to human error and technological deficiencies. The aim of this study is to investigate the impacts of digitization on board ships and how maritime safety is affected. The method used to investigate the effects of digitization is a systematic qualitative literature study. Balanced search terms and a structured selection of articles resulted in a total of twenty-two included articles that were analyzed. The content of the studied articles was thematized and presented in the study results divided into four main themes with one additional sub-theme each. The study shows that digitization can lead to efficiency, cost savings, and environmental benefits. Digital technology has the potential to facilitate decision-making for ship operators and the work of navigation can be facilitated with autonomous elements. An increased proportion of autonomous elements can lead to the operator’s knowledge being lost. Even if digital technology is reliable, it is created by humans, which can mean that the technology has been affected by the human factor. Digital technology makes decisions in a pre-programmed way and has difficulties in making overall assessments in complex situations. Unmanned ships may become a reality and the ship officers’ duties may change accordingly. Due to technology's lack of human common sense, ship officers can contribute to maritime safety. In the future, new demands may be placed on ship officers and knowledge of advanced technology, autonomous systems, and the ability to remedy errors that arise in the technology. To prepare the ship officers, flexible training systems can help to prepare operators for their coming profession. The maritime industry's adaptation to digitization can be facilitated through cooperation between regulatory authorities, organizations, and humans.

This study aims to identify risk factors among young boys that might lead to criminal behavior and actions. The study is based on four books, written by former criminals, a lawyer that has been working with the cold shooting cases in Sweden and two reporters from the exposed areas. By reading the books we could identify similar risk factors among the participants in the books that have got their story told. Since social worker's job is to help prevent criminal behavior among youth and young children by identifying the risk factors, we thought that this study could be helpful. The books produce important knowledge from reality. The study is divided into seven different themes in which risk factors can be found. Those are risk factors related to firearm-related violence, risk factors within the individuals, the families, school, socioeconomic status, substance use and social capital. First the study presents previous scientific studies, in the same seven themes, and then they are put together with the new findings from the books. From this study we can also find that the risk factors are influenced by each other, and that individuals are more likely to have several risk factors if they already have one. Depending on how the individuals identify and manage the risk factors, it is different how much they are affected by it. A risk factor that one individual has, does not have to be a risk factor for another individual. Due to this, social workers have to pay attention to every individual youth and consider their situation regarding risk factors for criminal behavior.

This is a study on the emigration from Blekinge County with a focus on Medelstads härad to Denmark and Germany, during the period 1870-1925. By measuring statistics on how many people emigrated from Medelstads judicial district 13 parishes to Denmark and Germany respectively the aim is. To get a new perspective on the less known emigration. From this the study can continue to examine female and male emigration from the parishes of Backaryd, Edestad, Listerby and Ronneby. Furthermore, the study will examine the professional titles and other titles that the emigrants had when they chose to emigrate. Based on the results of the first questions, it is possible to see which similarities and differences are found between the emigration to Denmark and Germany. The results indicates the a greater number of emigrants went to Denmark than to Germnay. The results between the male and female emigration indicates that the female emigration was moe extensive than the male emigration both to Denmark and to Germany. Regarding the occupational titles, it can be determined that it was occupations that belonged to the working class that most emigrants had when they emigrated from Medelstads härad. From these results, it is possible to find similarities and differences betwwen the migration to Denmark and Germany.