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Introduction Subintimal angioplasty (SIA) was introduced in the late 1980s and is a supplement to bypass surgery. Adaptation of the technique has been hampered by high rates of early intervention to maintain patency, but the long term assisted patency is good. Report The superficial femoral and popliteal artery containing a patent subintimal canal were explanted from a patient who died in the authors' ward. Histological analysis indicated that the lumen was created in the medial layer of the vessel wall. A collagen rich neointima and fragmented internal elastic lamina were observed, presumably as a result of activated smooth muscle cells. The luminal surface was partly covered by a single layer of CD31, von Willebrand factor, and partly CD144 positive cells. An early atherosclerotic lesion was observed distally in the subintimal canal. Discussion Remodelling and neo-cellularisation of the vascular wall after SIA are described. Notably, hallmarks of early and late stage atherosclerotic disease were evident throughout the subintimal canal. These observations require confirmation in a larger number of specimens but underscore the need for surveillance after SIA., Highlights • The subintimal canal was created in the medial layer of the vessel wall. • Early and late stage atherosclerosis is observed throughout the subintimal canal. • Neo-cellularisation of single layer luminal cells is apparent in the subintimal canal. • The findings underscore the need for surveillance of subintimal canals.

Regulatory T cells (Tregs) are a heterogeneous cell population that can either suppress or stimulate immune responses. Tumor-infiltrating Tregs are associated with an adverse outcome from most cancer types, but have generally been found to be associated with a good prognosis in colorectal cancer (CRC). We investigated the prognostic heterogeneity of Tregs in CRC by co-expression patterns and spatial analyses with diverse T cell markers, using multiplex fluorescence immunohistochemistry and digital image analysis in two consecutive series of primary CRCs (total n = 1720). Treg infiltration in tumors, scored as FOXP3+ or CD4+/CD25+/FOXP3+ (triple-positive) cells, was strongly correlated to the overall amount of CD3+ and CD8+ T cells, and consequently associated with a favorable 5-year relapse-free survival rate among patients with stage I–III CRC who underwent complete tumor resection. However, high relative expression of the activation marker CD25 in triple-positive Tregs was independently associated with an adverse outcome in a multivariable model incorporating clinicopathological and known molecular prognostic markers (hazard ratio = 1.35, p = 0.028). Furthermore, spatial marker analysis based on Voronoi diagrams and permutation testing of cellular neighborhoods revealed a statistically significant proximity between Tregs and CD8+-cells in 18% of patients, and this was independently associated with a poor survival (multivariable hazard ratio = 1.36, p = 0.017). These results show prognostic heterogeneity of different Treg populations in primary CRC, and highlight the importance of multi-marker and spatial analyses for accurate immunophenotyping of tumors in relation to patient outcome.

We establish general versions of a variety of results for quasiconvex, lower-semicontinuous, and law-invariant functionals. Our results extend well-known results from the literature to a large class of spaces of random variables. We sometimes obtain sharper versions, even for the well-studied case of bounded random variables. Our approach builds on two fundamental structural results for law-invariant functionals: the equivalence of law invariance and Schur convexity, i.e., monotonicity with respect to the convex stochastic order, and the fact that a law-invariant functional is fully determined by its behaviour on bounded random variables. We show how to apply these results to provide a unifying perspective on the literature on law-invariant functionals, with special emphasis on quantile-based representations, including Kusuoka representations, dilatation monotonicity, and infimal convolutions.

European transport policies have over the last decades advocated the CO2 efficiency of maritime transport relative to road haulage, and consequently, shipping reaping the benefits of being considered the green mode of freight transport. To date, research focusing on CO2 emissions from ships has to a great extent followed a modeling approach, based on a set of more or less well-founded assumptions. Yet these presumptions raise questions regarding the reliability of the emission results presented and the foundation of which transport policies are built upon. In an attempt to broaden the discussion, this paper presents CO2 emissions that have been calculated based on data from actual container feeder operations in Europe over a full year of service. Through the development of origin-destination matrices representing these real container flows, a mode-comparative analysis of CO2 efficiency is undertaken by constructing a counterfactual road transport alternative serving the same market. Although the results generally corroborate the environmental superiority of short sea container shipping with respect to CO2 efficiency, the comparative edge seems to be marginal in some scenarios. Thus, highlighting the need for shipping services to obtain a fairly high capacity utilization in order to still represent the green mode of transport in terms of CO2 emissions.

Flourescence-based multiplex immunohistochemistry (mIHC) combined with multispectral imaging and digital image analysis (DIA) is a quantitative high-resolution method for determination of protein expression in tissue. We applied this method for five biomarkers (CDX2, SOX2, SOX9, E-cadherin, and β-catenin) using tissue microarrays of a Norwegian unselected series of primary colorectal cancer. The data were compared with previously obtained chromogenic IHC data of the same tissue cores, visually assessed by the Allred method. We found comparable results between the methods, although confirmed that DIA offered improved resolution to differentiate cases with high and low protein expression. However, we experienced inherent challenges with digital image analysis of membrane staining, which was better assessed visually. DIA and mIHC enabled quantitative analysis of biomarker coexpression on the same tissue section at the single-cell level, revealing a strong negative correlation between the differentiation markers CDX2 and SOX2. Both methods confirmed known prognostic associations for CDX2, but DIA improved data visualization and detection of clinicopathological and biological associations. In summary, mIHC combined with DIA is an efficient and reliable method to evaluate protein expression in tissue, here shown to recapitulate and improve detection of known clinicopathological and survival associations for the emerging biomarker CDX2, and is therefore a candidate approach to standardize CDX2 detection in pathology laboratories., Digital image analysis (DIA) of multiplex fluorescence-based immunohistochemistry and visual chromogenic evaluation of CDX2, SOX2, SOX9, E-cadherin, and β-catenin in colorectal cancer are comparable, recognizing prognostic value of CDX2 and negative correlation with SOX2. Membrane staining is best evaluated visually, while DIA enables single-cell coexpression analysis and improves visualization and detection of clinicopathological and biological associations.

We study the problem of optimising the aggregated utility within a system of agents under the assumption that individual utility assessments are law-invariant: they rank Savage acts merely in terms of their distribution under a fixed reference probability measure. We present a unifying framework in which optimisers can be found which are comonotone allocations of an aggregated quantity. Our approach can be localised to arbitrary rearrangement invariant commodity spaces containing at least all bounded wealths. The aggregation procedure is a substantial degree of freedom in our study. Depending on the choice of aggregation, the optimisers of the optimisation problems are allocations of a wealth with desirable economic efficiency properties, such as (weakly, biased weakly, and individually rationally) Pareto efficient allocations, core allocations, and systemically fair allocations.

This paper explores container port system evolution and port choice from the perspective of a regional or secondary (feeder and short sea) system. Theory predicts that large-scale container port sy...

Formålet med denne oppgaven har vært å belyse samspillet mellom teknologisk utvikling og etterspørselen etter arbeid. Målet er å øke innsikten i hvordan teknologisk utvikling påvirker etterspørselen etter ulike typer arbeidskraft, og å studere hvilke konsekvenser innføringen av ny teknologi har hatt historisk i Norge. Jeg presenterer en grundig gjennomgang av aktuell økonomisk teori og empirisk litteratur. Finanssektoren blir deretter brukt som utgangspunkt for analysen, hvor hensikten er å undersøke om vi kan observere store endringer i sysselsettingen og sammensetningen av arbeidsstokken mellom år 2000 og 2018. Dette er en periode hvor finansnæringen er sterkt preget av teknologisk utvikling og omstilling. Datagrunnlaget og analysene har jeg gjennomført med registerdata fra Microdata.no. Gjennom en deskriptiv analyse viser jeg at utdanningsnivået har økt raskere i finansnæringen enn i Norge som en helhet. Økende utdanningsnivå skyldes ikke først og fremst en foryngelse av arbeidsstokken, men et økende utdanningsnivå på tvers av aldersgrupper. Vi kan observere oppgraderende tendenser i næringen. Med oppgradering refereres det til en økning i andelen sysselsatte med høy lønn/utdannelse, mens andelen sysselsatte med lav lønn/utdannelse synker. I tillegg ser vi at utdanningsnivået har stor betydning for lønnsutsiktene, hvor et økende erfaringsnivå gir større utslag i lønn for de med høyere formell utdanning. Ved bruk av en logistisk multinomisk regresjonsanalyse finner jeg statistisk signifikant korrelasjon mellom sannsynligheten for å bli værende i finansnæringen og flere individspesifikke forklaringsvariabler. Funn peker i retning av at yrkeserfaring i stor grad kompenserer for manglende formell utdanning i næringen, men at utdanningsnivået har mye å si for fremtidig lønnsutvikling og forutsetningene for å lykkes utenfor næringen. Vi kan observere tendenser til en U-formet mobilitetskurve, hvor de med høy lønn/utdannelse og lavere lønn/utdannelse har større sannsynlighet til å bytte næring. Det indikerer et mer polarisert arbeidsmarked. Det økende utdanningsnivået i samfunnet generelt, sammen med økt kompetansebehov i næringen, har gitt vanskeligere forhold for de uten høyere formell utdanning å entre finansnæringen. Selv om denne analysen ikke kan avdekke kausale sammenhenger mellom teknologisk fremgang og endringene i sysselsettingen i finansnæringen, understøtter resultatene det teorien sier om konsekvensene av teknologisk endring. Masteroppgave ECON391 PROF-SØK MASV-SØK

Introduction: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness. Methods: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group. The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness. Ethics and dissemination: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations. Trial registration number: NCT04586517.

In this paper we analyse in the framework of constructive mathematics (BISH) the validity of Farkas' lemma and related propositions, namely the Fredholm alternative for solvability of systems of linear equations, optimality criteria in linear programming, Stiemke's lemma and the Superhedging Duality from mathematical finance, and von Neumann's minimax theorem with application to constructive game theory.

Objectives To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND) Material and Methods Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Results Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10–27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1 Conclusion Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard ratio = 4.41, 95% confidence interval: 1.45–13.38; P = 0.009) in a Cox proportional hazard models, adjusted for Cancer of the Prostate Risk Assessments Post-surgical (CAPRA-S) score and perineural invasion. Decision curve analyses suggested an improved standardized net benefit, ranging from 0.06 to 0.18, of adding MVP onto CAPRA-S score. This observation was confirmed by receiver operator characteristics curve analyses for the CAPRA-S score versus CAPRA-S and MVP score (area under the curve: 0.58 versus 0.73). From these analyses, one can infer that MVP levels in combination with CAPRA-S score might add onto established risk parameters to identify patients with lethal prostate cancer., Mass spectrometry of an explorative cohort identified a promising biomarker, major vault protein. Using two independent validation cohorts, we verified an association between high MVP and adverse outcome. MVP was associated with prostate cancer-specific death independently of a composite risk model.

Robust models in mathematical finance replace the classical single probability measure by a sufficiently rich set of probability measures on the future states of the world to capture (Knightian) uncertainty about the "right" probabilities of future events. If this set of measures is nondominated, many results known from classical dominated frameworks cease to hold as probabilistic and analytic tools crucial for the handling of dominated models fail. We investigate the consequences for the robust model when prominent results from the mathematical finance literature are postulate. In this vein, we categorise the Kreps-Yan property, robust variants of the Brannath-Schachermayer Bipolar Theorem, Fatou representations of risk measures, and aggregation in robust models., 37 pages

Background: There is a need for improved selection of patients for adjuvant chemotherapy after resection of non-metastatic colorectal cancer (CRC). Regulator of chromosome condensation 2 (RCC2) is a potential prognostic biomarker. We report on the establishment of a robust protocol for RCC2 expression analysis and prognostic tumour biomarker evaluation in patients who did and did not receive adjuvant chemotherapy. Materials and Methods: RCC2 was analysed in 2916 primary CRCs from the QUASAR2 randomised trial and two single-hospital Norwegian series. A new protocol using fluorescent antibody staining and digital image analysis was optimised. Biomarker value for 5-year relapse-free survival was analysed in relation to tumour stage, adjuvant chemotherapy and the molecular markers microsatellite instability, KRAS/BRAFV600E/TP53 mutations and CDX2 expression. Results: Low RCC2 expression was scored in 41% of 2696 evaluable samples. Among patients with stage I–III CRC who had not received adjuvant chemotherapy, low RCC2 expression was an independent marker of inferior 5-year relapse-free survival in multivariable Cox models including clinicopathological factors and molecular markers (HR 1.45, 95% CI 1.09 to 1.94, p=0.012, N=521). RCC2 was not prognostic in patients who had received adjuvant chemotherapy, neither in QUASAR2 nor the pooled Norwegian series. The interaction between RCC2 and adjuvant chemotherapy for prediction of patient outcome was significant in stage III, and strongest among patients with microsatellite stable tumours (pinteraction=0.028). Conclusions: Low expression of RCC2 is a biomarker for poor prognosis in patients with stage I–III CRC and seems to be a predictive biomarker for effect of adjuvant chemotherapy.

Denne rapporten setter søkelys på egenskapene til massivtre og bindingsverk når materialene brukes i byggmoduler. Industrialisering av byggeprosessen ved bruk av moduler har økt både effektiviteten og rasjonaliteten i byggenæringen i dag. Det er stort potensiale og gode fremtidsutsikter både når det gjelder moduler generelt og for bruk av trematerialer i moduler. Massivtre er et nokså nytt materiale, og det er så langt ikke vanlig å produsere moduler i Norge med dette som hovedmateriale. Gruppen ønsker derfor å gjøre en sammenligning av moduler med massivtre og bindingsverk, og til slutt presentere et forslag til hvordan moduler av hovedsakelig massivtre kan utføres. Tanken er at disse modulene skal være så fleksible som mulig, altså at de er i stand til å imøtekomme ulike funksjoner og forskjellige byggeprosjekter. Prefabrikasjon og prekapp er tiltak som kan bidra til å redusere og håndtere avfalls-mengdene på byggeplasser. Ved å flytte produksjonen av byggmoduler til innendørs fabrikker kan arbeidet enklere standardiseres og dermed effektiviseres. Produksjon av moduler i fabrikker vil redusere byggefeil og øke kvaliteten på sluttproduktet. Tidlig og grundig planlegging er avgjørende for at byggmoduler skal være hensiktsmessige i byggeprosjekter. Høy byggeaktivitet i Norge sammenlignet med resten av Europa har ført til økt import av prefabrikkerte elementer og moduler fra hovedsakelig Øst-Europa, hvor arbeidskraft og materialer er billigere. De største fordelene med prefabrikasjon er kortere byggetid, bedre kvalitet og forutsigbar økonomi i prosjektene. Den tradisjonelle byggemetoden i Norge er bindingsverk, mens høyere bygninger stort sett har blitt oppført i betong og stål. Det er på tide å bruke kunnskapen om massivtre som et miljøvennlig og bærekraftig materiale til bygging av alt ifra småhus til store og komplekse bygninger. Massivtre har god bæreevne og brannmotstand, og kan være et godt alternativ når bindingsverk kommer til kort. Gruppen har gjennomført intervjuer av flere element- og modulprodusenter. Mange av produsentene har ikke erfaring med massivtre, og er noe skeptiske til materialet, blant annet fordi det er såpass nytt i norsk sammenheng. De produsentene som derimot har erfaring med massivtre påpeker at materialet kan løse mange utfordringer som ikke lar seg løse like lett med bindingsverk, men at det er viktig at entreprenører har kunnskap om hvordan massivtrekonstruksjoner bør utføres, hvordan massivtre reagerer på fukt og hvordan de derfor må beskyttes. I Norge må kunnskapen angående massivtre økes, slik at flere ønsker å ta i bruk teknologien. Hvis det blir større tilgang på massivtre vil prisen sannsynligvis gå ned over tid, noe som er avgjørende for konkurransen. Byggsektoren utgjør i dag 40% av klimagassutslippene verden over. Reduksjon innen denne næringen vil derfor bidra til å løse mange av problemene verden står ovenfor. Resultatene i rapporten viser at moduler med massivtre har bedre brannmotstand enn moduler med bindingsverk. Dette betyr at moduler i massivtre bevarer sin stabilitet og bæreevne under et helt brannforløp. Moduler i massivtre kan branndimensjoneres for å stå like lenge som de fleste mur- eller betong konstruksjoner og kan trygt brukes til bærekonstruksjoner i høye og komplekse bygg. Rapporten viser at det generelt er vanskelig å løse fuktproblematikken under transport, lagring og montering av begge modultypene. Både produsenter og entreprenører må alltid ha dette i bakhodet, slik at man unngår fuktskader i bygningene. This report seeks to highlight the difference of the technical characteristics of cross laminated timber (CLT) and timber frame structures when these materials are used in building modules. Industrialisation of the building process by using modules in large scale has increased both the effectivity and rationality of the construction industry. There is great potential and prospects when it comes to modules in general as well as the use of wood in modules. CLT is a rather new material, and producing modules using this material is not common in Norway. The bachelor group therefore want to compare modules with CLT and modules with timer frame structures, and in the end of this report present a system of how CLT modules can be built. The idea is that the modules should be as flexible as possible, to meet different functional requirements in different building projects. Prefabrication and “precut” can contribute to the reduction and handling of waste in building sites. By moving the production of modules to inside factory halls the work can be standardised and made more efficient. The production of modules in factories will reduce production errors and improve the quality of the product. Early and thorough planning is crucial in making the modules suitable to each building project. High construction activity in Norway compared to other parts of Europe has led to high import of prefabricated modules, especially from Eastern Europe, where costs of labour and materials are lower. The greatest advantages of prefabrication are shorter construction time, better quality, and predictability of economics. The traditional building method in Norway is timber frame structures, while large and tall buildings often are built using concrete and steel. It is about time that we start to use the knowledge regarding CLT as a green and sustainable material in the construction of everything from small houses to large and complex buildings. CLT has a high load bearing capacity, is good with regards to fire safety, and can be a good alternative when timber frame structures cannot meet the requirements. The bachelor students have interviewed several companies who produce elements and modules. Some of the companies do not have experience using CLT, and are a bit sceptical to the material, mainly because it is rather new in Norway. However, the companies who do have experience with CLT say that the material can solve a lot of problems that are hard to solve using timber frame structures. They also point out that the construction companies who builds with CLT need to have sufficient knowledge about the material, how it reacts to moist and how it should be protected. The knowledge regarding CLT must be increased in Norway in general, so that more people will choose the material. This will most likely lead to lower prices in a long term. The construction industry constitutes 40 percent of the greenhouse gas emissions worldwide. A reduction of these emissions will help in solving the problems the world is facing. The results in this report show that modules with CLT are better regarding fire safety than modules with timber frame structures. This means that CLT modules stay stable and load bearing through a fire, and as long as concrete structures when planned correctly. The report also shows that solving issues regarding moist during transport, storage and assembling is difficult for both module types, but that it can be avoided by taking some precautions.

In the framework of Bishop’s constructive mathematics we introduce co-convexity as a property of subsets B of ${\left\{ {0,1} \right\}^{\rm{*}}}$, the set of finite binary sequences, and prove that co-convex bars are uniform. Moreover, we establish a canonical correspondence between detachable subsets B of ${\left\{ {0,1} \right\}^{\rm{*}}}$ and uniformly continuous functions f defined on the unit interval such that B is a bar if and only if the corresponding function f is positive-valued, B is a uniform bar if and only if f has positive infimum, and B is co-convex if and only if f satisfies a weak convexity condition.

We provide a characterization in terms of Fatou closedness for weakly closed monotone convex sets in the space of $${\mathcal P}$$ -quasisure bounded random variables, where $${\mathcal P}$$ is a (possibly non-dominated) class of probability measures. Applications of our results lie within robust versions the Fundamental Theorem of Asset Pricing or dual representation of convex risk measures.

We show constructively that every quasi-convex, uniformly continuous function $$f:C \rightarrow \mathbb {R}$$ with at most one minimum point has a minimum point, where C is a convex compact subset of a finite dimensional normed space. Applications include a result on strictly quasi-convex functions, a supporting hyperplane theorem, and a short proof of the constructive fundamental theorem of approximation theory.

We consider families of strongly consistent multivariate conditional risk measures. We show that under strong consistency these families admit a decomposition into a conditional aggregation function and a univariate conditional risk measure as introduced Hoffmann et al. (Stoch Process Appl 126(7):2014–2037, 2016). Further, in analogy to the univariate case in Follmer (Stat Risk Model 31(1):79–103, 2014), we prove that under law-invariance strong consistency implies that multivariate conditional risk measures are necessarily multivariate conditional certainty equivalents.