Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

BackgroundThe subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.Patients and methodsFifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were included in this OSLO-COMET substudy. In immunohistochemically stained sections, total (Ttot), helper (TH), cytotoxic (CTL), and regulatory (Treg) T-cells were manually counted in hotspots from the invasive margin (IM), intratumor (IT), and tumor adjacent regions to determine T-cell densities.ResultsA striking accumulation of T-cells was found in IM of both pCRC and CLM with much lower densities in the IT region, exemplified by Ttot of 2838 versus 340 cells/mm2, respectively, in CLM. The correlation at the individual level between T-cell densities in pCRC and corresponding CLM was poor for all regions and T-cell subtypes; for instance, the correlation coefficient (R2) for IM Ttot was 0.07. The IT TH : CTL and Treg : TH ratios were 2.94 and 0.44, respectively, in pCRC, and 1.84 and 0.24, respectively, in CLM.ConclusionThe observed accumulation of T-cells in the IM regions of pCRC and CLM with low penetration to the IT regions, combined with high TH : CTL and Treg : TH ratios, point to the presence of an immune suppressive microenvironment. T-cell densities of CLM differed markedly from the matched pCRC, indicating that to evaluate T-cell biomarkers in metastasis, the commonly available pCRC cannot serve as a surrogate for the metastatic tumor

A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer

Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published nextgeneration sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, and utilizing miRNA-tailored quality control and processing. Five miRNAs were identified as upregulated at multiple metastatic sites Mir-210 3p, Mir191 5p, Mir-8-P1b 3p [mir-141–3p], Mir-1307 5p and Mir-155 5p. Several have previously been implicated in metastasis through involvement in epithelial-tomesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The use of a publicly available pipeline facilitates reproducibility and allows new datasets to be added as they become available. The set of miRNAs identified here provides a reliable starting-point for further research into the role of miRNAs in metastatic progression

Libanonprosjektet som mastertema i musikkpedagogikk

Masterstudiene på Norges musikkhøgskole favner bredt og har mange nedslagsfelt. Masterarbeid om musikkformidling har vært utført både innenfor musikkpedagogikk (Sætre, 1994) og studieretningen for utøving med teoretisk fordypning i det utøvende masterstudiet, tidligere kalt utøving med fordypningsemne (se f.eks. Monsen, 1997). Her ble den første avhandlingen levert i 1993. I musikkterapi ble den første avhandlingen levert i 2003 og blant de ca 70 avhandlingene som har vært innlevert i perioden 2008–2013 har flere naturlig plassert seg innenfor fagområdet til NMHs Senter for musikk og helse som ble opprettet i 2008. På tross av denne store faglige og tematiske bredden har svært få masteroppgaver tatt opp den typen satsinger som Libanonprosjektet utgjør. Parallelt med den økende mengden av masterstudier og -studenter har spørsmål om utdanningskvalitet i høyere utdanning kommet på dagsordenen i større og større grad. Det har skjedd både med Kvalitetsreformen i høyere utdanning (Kirke-, utdannings- og forskningsdepartementet, 2001), Bolognaprosessen (Danish Bolognaseminar, 2003) og med den internasjonale forskningsinteressen mot utdanningskvalitet (Steensaker og Maasen, 2005). Utfordringen med å opprettholde og styrke utdanningskvalitet i masterstudiene har mange sider. Blant dem er spørsmålet om relevans, både i studiet som sådan, i innslaget av forskning i masterarbeidene og i disse arbeidenes tematikk for øvrig. I slike sammenhenger kan aktiviteten i Libanonprosjektet være et fruktbart utgangspunkt på flere måter. Innholdet i Libanonprosjektet er beskrevet i kapittel 1 i denne antologien. Her vil vi ta for oss den delen av prosjektet som omhandler musikk. Vi vil trekke fram noen sider ved det vi mener kan være særlig interessante i en diskusjon om masterarbeid og potensialet for kunnskapsutvikling. Slik vi ser det faller musikkprosjektet i fire hovedkategorier. Den første rommer arbeidet med palestinske flyktninger i leiren i Rashedieh, en leir som i det siste også har tatt imot palestinere med tidligere tilflukt i Syria. Den andre kategorien rommer musikkarbeid på skoler i det libanesiske samfunnet. Det gjelder både på grunnskole og videregående nivå og inkluderer i tillegg elevenes forhold til musikk utenfor skolen. I den tredje kategorien kommer bachelorstudentene på NMH sin prosjektpraksis i Libanon, slik den beskrives i kapittel 4. Den fjerde kategorien rommer samarbeidsprosjekt mellom Libanon og Norge. Til denne hører samarbeidet med Algarheim skole og Jessheim videregående skole. Sammenlagt åpner disse sidene ved prosjektet for flere typer masterarbeid som det lenge har vært behov for

Modelling of flexible slender systems for real-time simulation and control applications

The main contributions in the present thesis are the development of two mathematical models describing the motion and forces in slender mechanical systems like cables. The main advantage by the models proposed is the possible real-time simulation performance which often is lacking in traditional model formulations. The main problem is often twofold; inversion of a full matrix for each time step and high mechanical and numerical stiffness. High material stiffness and high wave velocity in the longitudinal direction is by far the most common reason for the stiffness problem, and this requires very short time steps. For many applications the axial dynamics is of minor interest. Thus, the solution may be to separate the transversal and longitudinal dynamics. Both models proposed enables separation of dynamics, and one does not require matrix inversion. Real-time models for cable systems are useful for both controller design and observer design. In the present study a new control concept for interconnection maneuvering is proposed. A towed body is controlled via the forces in the interconnection. These forces are adjusted by active positioning of the towing vessel. Long and non-stiff connections may require very high bandwidth in the towing vessel’s motion, and this is not always possible to fulfill. The proposed solution to this may be to introduce local actuators on the towed body to adjust the control forces. Trawling is an application where the cable models and control concepts proposed may be used in future development. This application was the basis for starting this study, and the results may enable further industrial development of this technology

Molecular and immune landscape of colorectal liver metastases

Colorectal cancer is a common cancer in both genders, and 50% develop metastases which is the dominating cause of death from CRC, most frequently located in the liver (CLM). Only 20% of patients with CLM are eligible for surgical resection. For the first time in a randomised study, the OSLO-COMET trial compared short-term outcome between open and laparoscopic resection in 280 patients. Laparoscopic resection had a significantly lower complication rate (19% vs 31%), shorter hospital stay (53 vs 96 hours) at a similar cost. The postoperative 90-day mortality was low (0.04%). The long-term outcome after CLM resection may be associated with molecular and immunological features. Based on analysis of samples from the OSLO-COMET biobank the most frequent mutations were located in the TP53, APC, KRAS, PIK3CA, SMAD4, and NRAS genes, and the cohort was enriched for consensus molecular subtype 2. Importantly, the identified transcriptomic changes suggested that immune activation had taken place in tumours exposed to neoadjuvant chemotherapy (NACT). Almost all analysed cases were microsatellite stable, which is associated with poor response to immunotherapy. Quantification of T-cell densities by immunohistochemistry in primary CRC and matched CLM showed low concordance. T-helper cell dominated with regulatory T-cells comprising up to 44%, suggesting immune suppression. T-cells accumulated in the invasive tumour margin, particularly in CLM. A short-interval (<9.5 weeks) between NACT exposure and CLM resection was strongly associated with high T-cell density, including cytotoxic T-cells. In conclusion, the short-term results of the OSLO-COMET trial support the use of laparoscopy for CLM resection. Analyses of molecular and immunological features suggested the presence of immune suppression in CLM, and that NACT induces a transient immune activation that could be exploited in future studies in combination with immune therapy

The Lebanon project as a master’s thesis theme

The current master’s programmes at the Norwegian Academy of Music (NMH) cover many subjects. The first programmes were introduced in the 1970s and included performance studies only. In the beginning of the 1980s, the Diploma in Music Education was created, which later was renamed Master of Music Education. In the 1990s, master studies combining performance and music theory were added, and in 2003 the first thesis in the Master of Music Therapy programme was published. Despite this growth in the scope of master’s programmes and master’s theses, very few theses have addressed topics such as the Lebanon project. Parallel to the increasing number of master’s students and theses, the issue of educational quality in higher education has emerged as a core priority. This has occurred in connection with the Quality Reform of higher education (Ministry of Education and Research, 2001), the Bologna Process (Danish Bologna seminar, 2003) and international scholarship on educational quality (Steensaker & Maasen, 2005). Among the challenges of maintaining and strengthening the educational quality of master’s programmes is the issue of relevance. This applies both to the programmes and the thematic content of master’s theses, including the research studies on which those theses rest. Directing interest towards projects such as the Lebanon project can increase the thematic relevance of all these aspects

A Trajectory Observer for Camera-Based Underwater Motion Measurements

This paper deals with the issue of estimating the trajectory of a vehicle or object moving underwater based on camera measurements. The proposed approach consists of a diffusion-based trajectory observer [1] processing whole segments of a trajectory at a time. Additionally, the observer contains a Tikhonov regularizer for smoothing the estimates. Then, a method for including the camera measurements in an appropriate manner is proposed