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Hovedmålet med kreftbehandling er å eliminere kreftceller og dette er tradisjonelt oppnådd ved kirurgi, bruk av giftige medikamenter (cellegift) og stråling. En ny og betydningsfull tilnærming til kreftbehandling kalt immunterapi, har derimot fått mye oppmerksomhet det siste tiåret; Her forsøker leger og forskere å utnytte immunsystemet vårt for å målrettet  ødelegge kreftceller. En nøkkelaktør i denne banebrytende tilnærmingen er en gruppe «drapsmenn» i immunsystemet kjent som cytotoxiske T-lymfocytter (CTL-er). Disse cellene har en bemerkelsesverdig evne til å oppdage kreftceller ved å gjenkjenne unormale molekyler på overflaten av kreftcellene - molekyler som friske celler ikke har. Når CTL-er gjenkjenner kreftcellene ødelegger de dem ved å frigjøre giftige molekyler som initierer kreftcellenes selvdestruksjon. 
 
Selv om betydelige innsats har blitt dedikert til å forstå hvordan CTL-er aktiveres og hvordan de gjenkjenner kreftceller, vet vi mindre om de påfølgende hendelsene inne i kreftcellene som fører til deres død. Fra før vet vi at CTL-er kan initiere to forskjellige typer celledød i kreft: den første, kalt apoptose, er en stille og ordnet prosess der kreftcellene krymper og brytes opp uten å varsle immunsystemet; den andre, kalt pyroptose, er en mer dramatisk prosess som involverer dannelse av åpninger i cellemembranen, noe som fører til at cellene svulmer opp og sprekker. Under denne cellebristen blir innholdet inne i cellene frigitt i omgivelsene, og dette kan fungere som 'faretegn' som kan stimulere en sterkere immunrespons mot kreftcellene. Betydningen av denne cellebristen for å forsterke anti-tumorresponsene vil bli undersøkt i dette prosjektet. 
 
Videre er vi fascinert av muligheten for å avdekke ytterligere, ennå ukjente, former for celledød indusert av CTL-er. Utforsking av disse dødsrelaterte prosessene i kreftcellene kan potensielt øke effektiviteten av immunterapi og bidra betydelig i den pågående kampen mot kreft.

The primary goal of most cancer therapies is to induce cancer cell death. Immunotherapy relies on the cytotoxic activity of lymphocytes such as natural killer cells (NKs) and cytotoxic T lymphocytes (CTLs) to achieve this. While a significant amount of research in immunotherapy focuses on the events within cytotoxic lymphocytes or at the interface between cytotoxic lymphocytes and cancer cells, less is known about the molecular mechanisms that orchestrate cancer cell death, particularly in the case of CTL-mediated death.
CTLs are known to induce two types of cell death in cancer: non-inflammatory apoptosis and proinflammatory pyroptosis. Pyroptotic cancer cells release proinflammatory signals that attract immune cells to the tumor site, thereby enhancing the anti-tumor response. Cell lysis is a common outcome of pyroptotic cell death. It is unclear whether lysis can be decoupled from pyroptosis in cancer cells and whether the proinflammatory properties of pyroptotic cancer cell death depend on lysis. Moreover, it remains unknown whether CTLs can induce other forms of cell death in cancer, apart from apoptosis and pyroptosis.
Studying the mechanisms of CTL-mediated cancer cell death is challenging because CTLs selectively target cells expressing specific antigens. However, given the critical role of CTLs in immunotherapy, it is essential to deepen our understanding of CTL-induced cancer cell death.
This project aims to develop novel methodologies to investigate the death mechanisms that are initiated by CTLs. In addition, we will identify new pathways and mediators involved in CTL-induced cancer cell death. Furthermore, we will assess the contribution of proinflammatory cell death and lysis in promoting anti-tumor responses in vivo. Overall, this research will improve our knowledge of the molecular mechanisms of CTL-mediated cancer cell death and potentially reveal novel targets to enhance the efficacy of cancer immunotherapy.

T-cell-mediated proinflammatory cell death and lysis in cancer

En av de vanligste, men minst studerte, utfordringene med å bli eldre er problemer med å kommunisere. Mange eldre sliter spesielt med pragmatiske ferdigheter, som å forstå undertekst, eller tilpasse det de sier til personen de snakker med. 

La oss si at en lege må gi en alvorlig beskjed til en pasient. For å gjøre det litt lettere å takle, bruker legen vagere språk, som "kanskje" i stedet for "sannsynligvis". Mens yngre voksne ofte tar hensyn til høflighetsstrategier i måten de tolker det som blir sagt på, har eldre ofte vanskelig for å forstå når noen snakker indirekte. Mange eldre voksne har vanskelig for å forstå ikke-bokstavelig språk og kan misforstå alvorlighetsgraden av diagnosen. Dette kan påvirke beslutningen deres om behandling, noe som kan føre til utilsiktede konsekvenser. 

Siden god kommunikasjon er viktig både i viktige medisinske samtaler og i hverdagen, er det viktig at vi finner ut hva som gjør at eldre kan ha vansker med å forstå og bli forstått. RESILIENCE skal hjelpe til med denne utfordringen ved å samle data om praktiske, kognitive og språklige ferdigheter hos voksne i alderen 18-90 år over tid. Dette vil gi oss en stor mengde data om pragmatiske, kognitive og språk ferdigheter og gjøre det tilgjengelig for forskning. Med denne dataen som grunnlag har vi følgende mål: 

• Forstå hvordan praktiske evner endrer seg generelt gjennom voksenlivet. 
• Finne ut hvilke mekanismer som påvirker pragmatiske evner på forskjellige tidspunkter i livet.
 • Utvikle en teoretisk modell som forklarer hvordan pragmatiske ferdigheter endrer seg med alderen.
 • Lage algoritmer som kan forutsi hvordan pragmatiske evner vil utvikle seg for enkeltpersoner i årene som kommer. 
• Utvikle og teste et verktøy som kan måle pragmatisk helse (både pragmatiske ferdigheter og deres underliggende mekanismer), noe som kan åpne  for å iverksette tiltak. 

Dette vil gi oss muligheten til å forstå bedre hvordan folk kan utvikle pragmatisk resiliens gjennom livsløpet.

A cornerstone of human communication is our reliance on pragmatic skills to guide linguistic interactions (e.g., reasoning about others' mental states to bridge the gap between what is said and intended in conversation). However these skills are highly sensitive to age-related decline, leading to miscommunication and uninformed decision making in the older adult population. This raises an important question, one which has puzzled linguistics and psychologists for decades: if pragmatic competence is fundamental to communication, why do individuals vary so much in this capacity? 

Traditionally, psychologists have approached pragmatic competence from a cognitive angle, reasoning that individual differences in executive functions (i.e., the cognitive skills associated with goal-directed actions) are what underlie effective pragmatic behavior. In a similar vein, language scientists have taken a linguistic approach, reasoning that one’s language background (e.g., the frequency with which individuals shift between languages) shapes pragmatic skills by enhancing sensitivity to the communicative context. This focus on either cognitive or linguistic influences has resulted in two expansive yet disparate areas of research.

RESILIENCE will unite these disciplines to pursue a longstanding debate on what underlies pragmatic resilience and decline using a large-scale, interdisciplinary and longitudinal approach. By gathering data on adults' (ages 18-90) pragmatic, cognitive and language skills over multiple time points, we will develop a comprehensive theoretical model that explains how cognitive and linguistic systems interact to shape pragmatic competence as we age, and create algorithms that predict the trajectory of an individual’s pragmatic abilities in upcoming years. Based on these results we will design a multidimensional tool that detects the earliest signs of pragmatic deficits, leading to future interventions, allowing us to uncover the paths to pragmatic resilience.

Uncovering the paths to pragmatic resilience

Noen av oss tåler stressende livshendelser godt. Andre derimot utvikler vedvarende fysiske og psykiske plager som følger av stress. Hvor godt vi håndterer stress avhenger av et komplekst samspill mellom miljøfaktorer, sosiale forhold, biologisk sårbarhet og indre motstandskraft. Forskning på stressreaksjonene til dyr og pasientgrupper som til vanlig lever under mye stress viser at en gruppe signalstoffer i kroppen som aktiverer det samme hjernesystemet som cannabis – endocannabinoidene – kan begrense styrken på stressreaksjoner og bidra til at man raskere kommer seg til hektene. I dette prosjektet skal vi undersøke hvordan mestring av stress på kort og lang sikt henger sammen med nivåer av endocannabinoider i kroppen for å forstå hvorfor noen personer er mer motstandsdyktige mot stress enn andre. I den ene studien følger vi pasienter som skal gjennomgå en stressende, men veldig vanlig, situasjon: kirurgi. Her måler vi pasientenes opplevelse av stress, samt mentale og fysiske helse, fra tiden før til to år etter operasjonen og undersøker hvordan dette henger sammen med nivåene deres av endocannabinoider og andre stresshormoner. I den andre studien bruker vi data fra et eksperiment hvor deltakerne har blitt utsatt for psykososialt stress til å undersøke om endocannabinoidnivået deres påvirker hvordan de reagerer på stress, og om stresset i seg selv kan påvirke kroppens produksjon av endocannabinoider. Til syvende og sist er målet med studien å vurdere hvorvidt målinger av endocannabinoidnivåer kan brukes til å forebygge helseplager og til å evaluere behovet for økt oppfølging etter alvorlig stressende påkjenninger i livet.

In the face of major life stressors, some individuals cope well whereas others develop ill health and long-term adverse outcomes. Predicting who needs additional support in response to major life stressors is essential for targeted prevention and more efficient allocation of resources. The endocannabinoid system is emerging as a promising target for understanding vulnerability and resilience to stress. This system appears to buffer stress in two ways: by limiting the magnitude of the stress response, and by facilitating recovery after a stressful event. While the early findings are intriguing, they mainly stem from studies in rodents and small clinical groups with high stress burden. What role endocannabinoids have more globally for human resilience, health and well-being remains elusive. 

In this project we address this gap by leveraging comprehensive experimental and clinical data on two potent stress models: psychosocial stress and surgery. Drawing on these unique datasets, which combine experimental control with ecological validity, we will decipher how endocannabinoid levels influence people’s stress response and recovery across minutes, days, weeks and years. The project represents a novel directional shift for endocannabinoid research and will (i) determine the value of endocannabinoid levels as a biomarker to predict outcomes after surgery, (ii) quantify sex differences, (iii) assess endocannabinoid interplay with opioid analgesics, sex hormones and other stress markers (iv) spearhead open and reproducible science practices in endocannabinoid research, and (v) make this fine-grained and novel data available through an interactive web application. 

This project represents an ambitious effort to understand endocannabinoids’ role in stress resilience and will determine the value of endocannabinoids as a predictive biomarker and potential target for individualized treatment.

Deciphering endocannabinoid stress buffering in humans: 
Mechanistic and clinical investigations

WHeelchair Activity Monitoring project (WHAM)

Wheelchair users (WCU) are three to five times more inactive than the general population, leading to a high risk of developing preventable secondary conditions. Although physical activity (PA) guidelines have been specifically developed for WCU, we lack systematic approaches to implement them in practice, as well as valid algorithms to monitor PA change in WCU through sensor-based solutions. Accordingly, the overall scientific aim of the WHeelchair Activity Monitoring project (WHAM) is to advance PA research and practice in WCU by developing valid digital markers for monitoring of and providing feedback on PA, paving the way for implementation and intervention. I will accomplish this through combining the complementary research fields of 1) behavioural intervention studies focusing on increasing PA in WCU (core competence University of British Columbia, UBC; outgoing phase) and 2) sensor-based PA monitoring (core competence Norwegian University of Science and Technology, NTNU; returning phase – consolidated by non-academic placement at Maastricht Instruments, which develop research prototypes including PA monitors). WHAM’s scientific aim is achieved through three objectives: 1) Measure the effect of a pragmatic exercise intervention trial on self-reported physical activity levels and cardio-respiratory fitness, 2) Develop valid algorithms for tracking PA markers in WCU, and 3) Co-create a framework that outlines how PA can be conjointly monitored and provided feedback on in WCU. This fellowship will enable me to become established as an internationally recognized researcher in the field of “physical activity and disability”, while bringing together ongoing national disjointed research activities in this field. Altogether, my overall ambition is to contribute to reducing inequalities in daily-life participation among WCU compared to the rest of the population.

The goal of the Bilingual Experiences, Cognitive Ageing and underlying Mechanisms (BECAME) project is to examine the functional neuroplastic mechanisms underlying mitigatory effects of bilingual experience on age-related cognitive decline. While evidence is available for structural brain changes supporting bilingualism-induced effects on cognitive aging (CA), functional mechanisms underlying such effects are not yet well understood. BECAME aims to fill this gap by investigating the trajectory of bilingualism-induced functional neuroplasticity across the adult lifespan (ages 18-85), crucially adopting an individual differences approach related to measurable degree of bilingual engagement. Importantly, although such benefits are thought to be rooted early in the lifespan, evidence for the timeframe and conditions of their early emergence is scarce. The choice of including the whole adult lifespan allows us to investigate these mechanisms and their emergence more directly from a lifespan perspective. I combine behavioral testing with brain recordings via electroencephalography (EEG). EEG is widely used in cognitive neuroscience to assess brain activity and the degree of communication between brain regions (functional connectivity) in response to stimuli and at rest. Combining behavioral and EEG modalities will allow me to test bilingualism’s effect on functional connectivity, as well as its consequences for functional efficiency, the minimum required neural activation to successfully perform a task. This will enable a detailed, evidence-based account of the protective effects observed in older-aged bilinguals, and how they are built from earlier life stages. By illuminating the relationship between multilingualism and resulting neurocognitive adaptations, BECAME will enable to capitalize on it as a health initiative, with manifold societal implications and the potential to be translated into actionable policies exploiting multilingualism to ameliorate effects of CA.

Bilingual Experiences, Cognitive Ageing and underlying Mechanisms

Per- og polyfluorerte stoffer (PFAS) er en stor gruppe menneskeskapte kjemikalier med høyt fluorinnhold som antas å ha negative helseeffekter. Kilder til PFAS kan være produksjon av vann-, varme- og flekkbestandige produkter og disse kjemikaliene er en del av hverdagen vår. PFAS påvirkning av biologiske systemer er ikke fullstendig forstått. Noen PFAS er antatt å øke risikoen for å utvikling av ikke-alkoholisk fettleversykdom (NAFLD) og øke risikoen for diabetes. 

For å forstå hvordan PFAS påvirker organene våre ønsker vi å bruke små laboratoriedyrkede organmodeller, kalt organoider. Disse miniatyrorganene kan dyrkes fra menneskelige stamceller og tilbyr et kontrollert miljø for å studere hvordan PFAS påvirker f.eks lever og bukspyttkjertelen vår, uten bruk av dyreforsøk.

For å studere helseeffekter må vi kunne måle nivået av biomolekyler som fettstoffer i leveren og hormoner i bukspyttkjertelen. Til dette trenger vi å utvikle analytiske verktøy for å måle effektene. Først vil vi bekrefte at når leverorganoidene eksponeres for enkelte PFAS-forbindelser utvikles det NAFLD-lignende sykdom ved å sammenligne den biokjemiske profilen (proteiner og metabolitter) til organoider av lever med PFAS-eksponerte organoider. Deretter vil vi utvide den analytiske verktøykassen for å undersøke hvilke metabolske veier som påvirkes, og om effekten er den samme i NAFLD-induserte og PFAS-eksponerte organoider. Vi vil også eksponere insulinproduserende bukspyttkjertelorganoider for PFAS for å undersøke effekten av PFAS på hormonproduksjon. Når effektene av PFAS-eksponering på lever- og bukspyttkjertel-organoider er etablert, vil organoidene bli samkultivert i en chip, og effektene av PFAS-eksponering vil bli undersøkt og sammenlignet med individuelle organoider.

Persistent organic pollutants (POPs) are believed to contribute to metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and type 1 diabetes. HE-POP aims to investigate the effects of per- and polyfluoroalkyl compounds (PFAS), a type of POPs), on organ function in a controlled environment.

Organoids are multicellular laboratory-grown miniature organs, that are grown from stem cells. HE-POP will use organoids to examine how PFAS affects our organs and develop cutting-edge bioanalytical tools and methodology to measure these effects using liquid chromatography-mass spectrometry. HE-POP hypothesizes that PFAS negatively affects organ function, as evidenced by changes in hormone and lipid levels characteristic of NAFLD and type 1 diabetes. 

Organoids offer a controlled environment to study the effects of PFAS on the liver and pancreas, without the use of animal models. HE-POP aims to gain evidence of the negative effects of PFAS on organ function through controlled experiments on organoids and aid in understanding the biological mechanisms underlying NAFLD and type 1 diabetes.

HE-POP has fundaments in UN sustainable development goals, specifically #3, #12, and #14/15, seeking an understanding of diseases with worldwide prevalence, and understanding how POPs affect our life and surroundings and help enable the right regulatory actions and replacement chemicals.

HE-POP: Studying the Health Effects of Persistent Organic Pollutants, Using Mass Spectrometry, Organoids, and Organ-On-A-Chip

Rundt 7% av norske 4-åringer har så store psykiske vansker at de kvalifiserer for en diagnose, men det tar ofte lang tid fra vanskene oppstår, til de blir oppdaget og barna får rett hjelp. Myndighetene har derfor lagt tydelige føringer for at de som jobber med barn, må vite hva de skal se etter og hvordan de skal gå frem for at barna skal få den hjelpen de trenger. I Norge går over 95% av barna i barnehage hvor pedagogene blir godt kjent med barna over tid i deres naturlige miljø og har utviklingssamtaler med de foresatte 1-2 ganger i året. Barnehagen skulle derfor være en ideell arena for tidlig oppdagelse av psykiske vansker. Det har imidlertid ikke vært tilgjengelig noen tilpasset metode for de arbeidsformene og terminologi som er vanlig i barnehagene. Vi har derfor utviklet metoden Dialogbasert tidlig oppdagelse (DBTO) i nært samarbeid med pedagoger og foreldre i 8 ulike barnehager. Metoden går ut på å bruke utviklingssamtalen mer systematisk ved at både foreldre og barnehagelærer på forhånd fyller ut et spørreskjema om mulige bekymringer de har hatt for barnets utvikling og trivsel de siste månedene. I samtalen kan de så utforske og forsøke å enes om forståelsen av barnet og om det er behov for ytterligere vurdering eller andre tiltak. Tilbakemeldingene under utviklingen og tidlig utprøving tyder på at metoden fungerer godt og oppleves som et nyttig verktøy i foreldresamarbeidet. For å få tydeligere dokumentert kunnskap om hvordan DBTO fungerer i barnehagene, har vi utviklet forskningsprosjektet PRO-DIALOG. Vi ønsker med det å få kunnskap om (1) hvordan DBTO fungerer som et screening-instrument, (2) hvor brukervennlig den er, (3) hvordan den påvirker tidspunkt for igangsetting av tiltak og (4) hvordan den påvirker utviklingen av den psykiske helsen til barna over tid. 12 barnehager er plukket tilfeldig ut til å gjennomføre metoden, mens 11 skal fungere som kontroller. Foresatte til rundt 300 barn som har tre år igjen av barnehagen, vil bli spurt om å delta.

There is an unambiguous call for early interventions at the municipal level for children at risk of developing mental health problems. However, there is a surprisingly absence of socially valid methods for detecting children in need of early support.
        The aim of the project is to establish the properties of such a novel method; Dialogue Based Early Detection (DBED). We will study its properties as a mental health screener, how well it is adapted in an ordinary kindergarten context, and whether it affects activation of interventions for mental health concerns and children’s future mental health.
        The novel aspect of DBED is the systematic assessment of the child’s development and well-being by the kindergarten teacher and his/her parents, and the subsequent dialogue that aims to explore and converge their understanding of the child and conclude whether there is a need for further assessment or supportive actions.
        Parents of approximately 300 children in 23 different kindergartens aged 2-3 years will be invited to participate for the three last years before school start and follow-up the next two years. The kindergartens will be randomized to an implementation group or a control group. Parents’ socio-demographic characteristics and data from parent-teacher meetings, initiated interventions, user satisfaction, parental stress, and child mental health will be collected biannually, as well as tape recordings from interviews about user experiences of parents and teachers.
        The most critical challenges of the project will be participation rate of the invited parents in addition to attrition due to the time pressures in a busy workday in the kindergartens, and willingness of the control parents to complete the repeated questionnaires. Appropriate measures are made to take those risks into account.

Promoting mental health in young children – a sustainable dialogue based approach in kindergartens (PRO-DIALOG)

InterNASH - An intercellular-pathway therapeutic for non-alcoholic steatohepatitis

Demografiske endringer fører til at andelen av befolkningen som er arbeidsfør er fallende. I tillegg til teknologisk utvikling og import av arbeidskraft vil det å beholde unge voksne i arbeidsstyrken i flere tiår være viktig for å kunne opprettholde en sterk velferdsstat. Samtidig viser studier en økende forekomst av psykiske plager blant unge vokse – spesielt depresjon og angst. Denne utviklingen gir grunn til bekymring, både for de unges helsetilstand og deres evne til å stå i arbeidsstyrken over tid.
Det finnes mange ulike forklaringer på økningen i rapporterte psykiske plager blant unge, som for eksempel bruk av sosiale medier, økt skolepress og et mer krevende arbeidsmarked. Samtidig har det blitt hevdet at økningen også kan reflektere et redusert stigma knyttet til psykiske helseproblemer, bedre behandlingstilbud og en økende tilbøyelighet til å søke medisinsk hjelp for psykisk ubehag som tidligere ble ansett som «normalt» , såkalt medikalisering.
YoungPsych-prosjektet vil undersøke om samfunnet har blitt mer eller mindre inkluderende for unge med psykiske helseproblemer, samt om unge voksne med psykiske problemer i dag har større (eller mindre) sannsynlighet for å fullføre utdanning og være aktive i arbeidsstyrken. Videre vil prosjektet belyse i hvilken grad skolepress, stressende arbeidsforhold og bruk av sosiale medier bidrar til økningene i psykiske helseproblemer blant unge. Ikke minst vil prosjektet undersøke i hvilken grad mer åpenhet om psykiske problemer og en økende tilbøyelighet til å søke medisinsk hjelp bidrar til den observerte økning i psykiske diagnoser.
For å besvare disse spørsmålene vil prosjektet benytte seg av norske registerdata og store befolkningsundersøkelser. Resultatene fra prosjektet vil kunne hjelpe beslutningstakere, forskere og den interesserte offentligheten til å bedre forstå de nylige økningene i psykiske helseproblemer hos ungdom og unge voksne, samt i hvilken grad dette kan forventes å påvirke arbeidsmarkedene i fremtiden.

A high rate of labor force participation is an important foundation of the Norwegian welfare state. At the same time, an increasing share of young adults is not participating in the labor market due to mental health problems. Moreover, the share of young adults seeking help for mental health problems is strongly increasing. Together with a demographic shift towards an older population during the next decades, these developments have stirred concerns regarding future cohorts' ability to participate in the workforce. Work force participation is both important for the welfare state and for an individual’s social and economic integration into society. 

Against that background, the YoungPsych-project will provide the best to-date knowledge about (i) the relationship between early-life mental health problems, educational attainment and labor market attachment; (ii) the impact of academic pressure and job characteristics on the likelihood of developing mental health problems; (iii) the extent to which a lower threshold for seeking help and a more widespread use of social media can explain the increase in mental health diagnoses.

With a highly competent interdisciplinary project team, the project will produce new knowledge that is highly likely to move the field forward. The empirical foundation of the project is a uniquely comprehensive register linkage, linked to population wide survey data from the Armed Forces' selection process, and large register-linked longitudinal population-based surveys. These data sources allow for examining changes during the past two decades and to take into account different aspects of mental health, including self-perceived mental health, help-seeking behavior and doctors’ diagnoses. The strength of the project lies in the combination of exceptionally rich longitudinal data, creative research designs, modern data analysis, and important and timely research questions.

Young adults’ mental health and labor market exclusion - causes, consequences, and trends

I denne randomiserte kontrollerte studien har vi som mål å optimalisere behandlingen av pasienter med juvenil idiopatisk artritt (JIA) som er i stabil remisjon. Å finne riktig behandlingsnivå hvor risikoen for sykdomsoppbluss er balansert med byrden av å ta medisiner og deres bivirkninger er svært viktig for pasienter, foreldre og helsepersonell.

JIA er den vanligste kroniske revmatiske sykdommen hos barn og ungdom, og rammer flest jenter. Sykdommen er karakterisert av leddbetennelser, og kan føre til leddskader og funksjonstap. Heldigvis, takket være moderne medisiner og behandlingsstrategier, kan mange JIA-pasienter oppnå "vedvarende remisjon" - uten symptomer på sykdommen.

Men fortsatt vet vi ikke: hvordan bør JIA-pasienter som er i remisjon best behandles? Det finnes ikke kontrollerte studier som veileder oss, og det foreligger ingen anbefalinger om hvorvidt behandlingen bør trappes ned eller avsluttes.

Derfor introduserer vi "MOVE-JIA": en nasjonal studie som vil inkludere JIA-pasienter i vedvarende remisjon behandlet med tumor nekrosefaktor-hemmere (TNFi) og metotreksat. De vil bli tilfeldig delt i tre grupper: A) Gradvis seponering av TNFi, B) Gradvis seponering av metotreksat, eller C) Fortsatt stabil behandling med både TNFi og metotreksat. Studiens hovedmål er å måle hvor mange pasienter i hver gruppe som opplever sykdomsoppbluss i løpet av et år.

MOVE-JIA studien vil bli den første studien som undersøker om å redusere metotreksat fører til færre sykdomsoppbluss sammenlignet med å redusere TNFi hos JIA-pasienter i remisjon. Studien vil også vurdere om behandling med kun TNFi eller kun metotreksat er like effektivt som kombinasjonsbehandling.

MOVE-JIA studien er et nasjonalt samarbeid som inkluderer alle barnerevmatologiske avdelinger i Norge og aktiv deltakelse fra pasientene. Dette sikrer rask overføring av resultater til klinisk praksis. Funnene vil gi etterlengtet kunnskap om hvordan vi best skal håndtere barn og ungdommer med JIA i remisjon.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and adolescents and occurs 3-6 times more often in girls. It is characterized by joint inflammation with a potential for joint destruction and disability if not treated. Sustained remission (no sign of active disease) is an achievable goal in JIA after the introduction of biological agents such as inhibitors of tumor necrosis factor (TNFi) and treat-to-target strategies. However, strategies to best treat JIA patients in remission remains unclear. No controlled studies have addressed the effect of tapering strategies for JIA in remission, and there are no current recommendations for stepdown or optimizing maintenance treatment. Given the risks, side effects and costs of JIA medications, treatment withdrawal can give patients and families relief and improve their quality of life. 
The MyJIA-Ahead trial is a national, investigator initiated, multicenter, 36 months, RCT of JIA patients in sustained remission on TNF-inhibitor and methotrexate. 150 JIA patients will be randomized 1:1:1 at baseline to A) Stepwise withdrawal of TNFi, B) Stepwise withdrawal of MTX, or C) Continued stable treatment with TNFi and MTX. The primary endpoint is proportion of patients with disease flare within 12 months. Key secondary endpoints are time to flare and time to regain remission after flare. If a disease flare occurs, the patient will return to the full dose study medication (the treatment the patient was receiving at baseline). Exploration of risk factors for disease flare includes patients reported health status and preferences, clinical characteristics, immunogenicity, molecular signalling (transcriptional, cellular and genetic risk) and ultrasound assessment of synovitis.

While evidence-based advice for starting therapies in active disease is available, The MyJIA-Ahead will provide much needed knowledge about treatment continuation in children and young adults with JIA in remission.

Moving towards evidence-based treatment strategies for children with juvenile idiopathic arthritis in sustained remission: The MOVE-JIAtrial

Midlene fra HAVBRUKS-Havbruk - en næring i vekst fordelt på år

Midlene fra HAVBRUKS-Havbruk - en næring i vekst fordelt på fylker

Midlene fra HAVBRUKS-Havbruk - en næring i vekst fordelt på fagområde

Professor

Norsk-kinesisk symposium/workshop innen akvakultur, sykdommer og genetikk

The proposed project aims to develop links and cooperation between the Norwegian Energy-Sustainability Nexus lab (ESNL) and the French Laboratoire de Biotechnologie de l'Environnement (LBE, INRAE). The interest of such a collaboration is to further develop the hydrogen production activities by dark fermentation of both laboratories by pooling their respective competences. The visits in both institutes of PhD students involved in the field will allow them to develop the skills mastered in the host laboratory, to integrate the European biorefinery network and thus to disseminate the acquired skills more widely. The use of industrial hydrogen in France is responsible for 3% of the country's greenhouse gas emissions. Indeed, 95% of the hydrogen currently used comes from the reforming of fossil fuels, emitting 10 kgCO2/kgH2. Hydrogen is an energy carrier of growing interest in the context of the development of intermittent renewable energies and to ensure clean mobility. It is therefore necessary to develop new modes of hydrogen production having the lowest environmental impact.
In this context, dark fermentation allows the production of hydrogen by biological degradation of organic waste under anaerobic conditions. The waste treatment and hydrogen production services provided by this process make it part of the bioeconomy and are currently attracting a lot of interest. Moreover, compared to hydrogen production by water electrolysis (as main technology for massive H2 production), dark fermentation emits 8 times less CO2 per kg of H2 produced and is therefore one of the least polluting hydrogen production processes.  However, the development of this process is restricted by low hydrogen productivities that impair the process competitiveness in regards to water electrolysis. These low yields result from the presence of  non-hydrogen producing microorganisms or the accumulation of inhibitors

Green hydrogen technology using food waste via thermophiles

The  global  trend  to  extend  connectivity  to  many  devices  for  everyday  use  lead  to  the emergence of Edge computing. A paradigm where data and services are gradually pushed from the cloud which allows edge-level data storage and processing, increasing responsiveness through lower communication delay and lower transmitted traffic volumes.  To allow this evolution, more and more devices (mobile devices as well) at the edge need to be mobilized and aggregated to compensate in the vast amount of resources previously offered by could-based services.  These devices  are  closely  related  to  human  activity  and  as  such  mobility  is  expected.   As  different  levels of mobility are observed, from mostly static sensors to highly dynamic connected vehicles, resource provisioning in dynamic environments on consumer devices emerged as a challenge, from the network to the application layer. To address this challenge, we aim to research on highly self-aware software services design model considering its own capabilities, limitations, anticipated needs, and associated contextual properties that we refer to as cognitive services. The cognitive services are autonomously deployed and orchestrated on the Edge-Fog-Cloud nodes and can migrate to other nodes due to, e.g., resource usage efficiency reasons, or for fulfilling dynamic accuracy and latency requirements.

To succeed, we intend to address the following research challenges:
  • Energy-aware resource provisioning in an heterogeneous mobile context
  • Dynamic and self-learned cognitive services migration between nodes
  • Mobility-aware churn tolerant device-to-device communication

We  propose  activities  involving  exchange  of  staff  and  PhD students, strengthening  both  groups  in  Norway  and  France  and  providing  easier  access  to  the  other  groups  methods.   It  will  also  encourage  research  collaboration  and trigger initiatives for long lasting collaboration through EU-funded projects.

Cross-Layer Cognition in Mobile Edge Computing (CroCoMilE)

Fluid flow in deformable porous media is of high relevance in both France and Norway. Applications  with a strong multi-physics coupling range from subsurface activities as CO2 storage, geothermal energy, and nuclear waste management, to biomedical engineering as studying Alzheimer’s and osteoporosis. Many of these applications involve several interacting fluids, necessitating the study of multi-phase poromechanics.

State-of-the-art, fully coupled poromechanics models used in practice simply merge existing, partially linearized single-physics models for flow and deformation. This results in thermodynamical inconsistencies (e.g. possibly negative porosity and fluid mass), which does not allow for unconditional well-posedness as well as the development of unconditionally robust numerical methods.

The main goal of the GradFlowPoro project is to develop a methodology for realiable simulation of multi-phase poromechanics. This encompasses modeling, and development and analysis of numerical methods. First, a novel, thermodynamically consistent model for multi-phase poromechanics with a variational gradient flow structure will be established. Based on that, structure-preserving discretization methods, as well as robust nonlinear solvers will be developed and analyzed. The numerical methods will be implemented and practically tested using the open-source numerical library PorePy, tailored to multiphysics subsurface simulations in complex media.

To reach the goals of the GradFlowPoro project, the complementary expertise of the chosen partners of this project are paramount. Synergy is expected from active exchange of knowledge and research practice, which will also support the two secondary goals of this project: (i) to establish a new collaborative research environment between the Norwegian and French institutions; and (ii) to increase research networks in particular among the young researchers involved.

Gradient Flow Modelling of Multi-phase Flow in Deformable Porous Media

Under this project, the partners will form a collaborative research project titled “Technology Roadmap for Autonomous Feeder Loop Service” (TRAFLS). Despite rapid technological developments toward fully autonomous systems for the transport and logistics industry, their commercial applications still limited and needs attention. For deployment of autonomous transportation services, one of the major challenge is ensuring changes required in other interdependent systems and connecting those systems in a safe and seamless manner.  
The aim of this collaborative project is to investigate the process for building a logistics system for waterborne freight feeder loop service utilizing autonomous systems including maritime autonomous surface ships (MASS).  The expected outcome is a blueprint for the development of the logistics system, assessment of the maturity of relevant technologies, and prediction of the timing of the real-world application of the seamless and safe autonomous logistics system for feeder loop service.   
The study will be conducted in three stages. The first stage includes a review of literature and existing logistics system of waterborne feeder services to identify the key technologies used, and that are under development. Second, based on Delphi study framework, the inventory of key technologies required for the logistics system is mapped and analysed. Finally, experts predict the maturity of the technologies and real-world application of the autonomous waterborne freight feeder loop service. The outcome of the study will help policy makers in the related industries gain a better understanding of development and usefulness of the key technologies.

Technology Roadmap for Autonomous Feeder Loop Service

For the characterization of Arctic scenario, synthetic aperture radar (SAR) sensing plays a key-role. SAR satellites provide measurements regardless of weather conditions and natural illumination with high spatial resolution. In particular, the Sentinel-1 mission is considered an important operational data source for sea ice classification. Sea ice classification from SAR relies on the fact that different ice types have different signatures in the image. These are generally related to the physical nature of the ice surface, such as roughness or dielectric properties, or system and geometric properties, such as frequency, polarization, noise level, and incidence angle (IA).  Unfortunately, signal ambiguities and additive system noise might vary across each single scene, making the automatic interpretation of the scenes very cumbersome, which is why ice charting is still a partly manual process. 
It is then paramount to address the operations of denoising in SAR data analysis, so to enable an accurate understanding of the Arctic scenario. This would then allow to provide a precise characterization of the physical phenomena occurring over the regions of interest. To achieve this goal, it is also important to obtain a robust understanding of the physical models causing the signals to be analyzed, so to improve the effectiveness of the aforesaid denoising phase. In this respect, considering multiple data sources (e.g., optical remote sensing, in situ measurements) could help in designing the automatic data analysis schemes. Finally, it is important to address the uncertainty of the outputs of the data analysis scheme, i.e., to provide a degree of confidence on the analysis outcomes. COSMIC will address these points, by taking advantage of the expertise gained by the group at Telecom Paris in efficient and effective SAR-based data analysis, and of the expertise of the group at UiT in characterization of Arctic scenarios by multimodal data analysis.

Advanced processing of SAR images for the Arctic

The introduction of minimally invasive surgery in the 90’s, together with an increased public attention to surgeons’ competencies in general, have created an interest in how to acquire and test surgical skills outside of the operating room.  In addition, organizational changes such as increased focus on improved efficiency in operating rooms and a further increase in complexity in surgical skills and technical tools have altered the premises for the traditional apprenticeship model. 
Simulation-based training that reproduce vital parts of the surgical reality appear as a promising adjunct to the apprenticeship model. Simulation-based training and assessment, however, require simulators together with training and assessment programs that have enough support of validity for the intended use. 
 The health department in Norway have during the last years made changes to the structure of surgical education. One of them is the introduction of simulation-based training as both a compulsory and recommended training activity for surgeons in training. This is regarded as a positive step forward, but a step that need support, both in creating simulation-based training programs that have enough scientific support for the intended use, and further to exploit the possibilities of competency-based education where simulators are used to assess surgical skills.  We plan to look into these aspects, where a collaboration across French and Norwegian education systems will give valuable insight into differences and similarities. 
We plan to define a multi-center study with the clinical partners to create knowledge on what are good simulation-based training and how and which surgical skills can be assessed with the simulators, with the intention to create evidence-based simulation-based training programs and skills assessment that can be implemented in surgical education in Norway and France

Simulation-based training and assessment in laparoscopic surgery

The project will study the adaptation and subcellular physiology of Arctic snow-algae, which have unique metabolic adaptations and could play roles in climate change. The project will use new research tools including selected techniques from the microbial and plant sciences to investigate how snow-algae adapt and respond to environmental changes, particularly the effects of high light and low temperatures on their cell membranes. The project will generate new types of data on snow-algae physiology and we expect that the results will help us understand more about how the cells adapt to extreme conditions and how they might respond to future changes in the Arctic environment.

Deciphering the physiology of Nordic snow-algae and cell membrane stress responses

Scientifically the project is concerned with a new way to harvest energy from sources accessible for in vivo devices. These sources can be of mechanical, thermal, or photonic nature, but within the body the energy that can harvested from each of them individually is rather small. In our novel approach we will investigate a material system that can harvest energy from all three of these sources simultaneously, meaning a system that shows piezoelectric, pyroelectric, and photovoltaic properties: BaTiO3 (BT). BT is an inorganic solid that is brittle in nature and therefore difficult to apply in vivo. We will therefore develop and investigate composite samples that consist of a flexible polymer matrix with BT embedded in nanoparticle form. The piezoelectric, pyroelectric, and photovoltaic response of these samples will be tested under single and multiple stimuli to clarify the interrelationship between the three different functionalities and determine the energy harvesting potential. As materials embedded into the body have to be chemically stable or show controlled dissolution, the chemical and functional stability of the samples will be investigated in the presence of simulated body fluid. 
This project will be conducted by several young researchers in the laboratories at NTNU and at Université Paris-Saclay, CNRS, CentraleSupélec. Mutual research visits that include workshops on topics fundamental to the project will broaden their technical expertise. Furthermore, the experience of working in an international research team can not be underestimated as it shows the variety in approaching scientific questions.
The project will serve as a seed to develop a large Innovative Training Network (ITN) including more collaboration partners all over Europe.

HAVBRUKS-Havbruk - en næring i vekst

Norsk-kinesisk symposium/workshop innen akvakultur, sykdommer og genetikk

Awarded: NOK 0.24 mill.

Funding scheme:

HAVBRUKS-Havbruk - en næring i vekst

Funding Sources

Thematic Areas and Topics