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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

Bilingual Experiences, Cognitive Ageing and underlying Mechanisms

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.

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.

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)

Dette prosjektet, kalt Hukommelse for musikk, fokuserer på det økende antallet mennesker over hele verden som lever med demens, spesielt Alzheimer's sykdom (AD). AD starter typisk med hukommelsesproblemer og påvirker etter hvert daglige aktiviteter. Aktive musikkintervensjoner, spesielt sang, har vist positive effekter på humør, atferd og livskvalitet for personer med demens, men deres innvirkning på kognisjon er ikke godt forstått. Prosjektet har som mål å fylle dette kunnskapsgapet ved å studere effektene av å lære nye sanger på kognitiv, atferdsmessig og hjernemessig funksjon.

Studien vil omfatte hjemmeboende voksne over 65 år med AD fra Argentina, Østerrike og Norge. Deltakerne vil gjennomgå 5 måneder med intensiv musikalsk opplæring (to ganger i uken) og 5 måneder med minimal opplæring (en gang i måneden) i tilfeldig rekkefølge, med en to måneders pause imellom. Intervensjonene inkluderer å lære nye sanger med en personlig musikklærer. Generell kognisjon vil bli målt ved bruk av Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog), og hukommelse for musikk vil bli vurdert gjennom ulike metoder, inkludert atferdsoppgaver og hjerneaktivitet (EEG). Humør vil også bli evaluert i hver økt.

Målet er å inkludere 113 deltakere for å sikre pålitelig påvisning av meningsfulle effekter. Studien vil utforske hvordan humør og hukommelse for musikk bidrar til endringer i kognitive evner, og om disse effektene varierer basert på faktorer som kjønn, alder, AD-stadium, eller tidligere musikalsk opplæring og generell utdanning. Prosjektet vektlegger samarbeid mellom forskere, tjenesteytere og brukere for å sikre studiens relevans og anvendelighet.

The number of people living with dementia is increasing and is high in low, middle, and high-income countries. Alzheimer’s disease (AD), the most common type of dementia, manifests itself initially with cognitive impairment in memory domains, and later affects all activities of daily living. Active music interventions, particularly singing, can help to improve mood, behaviour problems, and quality of life. Too little is known about their effects on cognition, although some promising studies exist. The M4M project aims to fill this gap by measuring effects of learning new songs on clinical, behavioural and brain functioning. Specifically, M4M aims to examine changes in general cognitive functioning and memory for music in non-musician adults with AD undergoing intensive individual musical training based on singing novel songs, compared to minimal training.
        Home-dwelling adults with AD, 65 years or older, in 3 countries (Argentina, Austria, Norway), will receive 5 months of intensive intervention (2x/week) and 5 months of minimal intervention (1x/month), in random order, with a 2-month break in between. Interventions will entail learning new songs with an individual music teacher. At the end of each intervention period, general cognition will be measured with the Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) by a person who is unaware of the intervention received. Memory for music will be tested with observations, behavioural tasks, and brain responses (EEG). Mood will be assessed in each session. We aim to include 113 participants; this will help us to reliably detect clinically meaningful effects. We will also examine how mood and memory for music lead to changes in cognitive abilities, and whether effects depend on sex, age, AD stage, or previous musical training or general education. M4M will be conducted in close collaboration between academic researchers, service providers, and service users to ensure relevance and applicability.

Memory for Music: Effects of individual intensive musical training based on singing in non-musicians with Alzheimer’s disease

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

Norske kvinner har den høyeste sykefraværsraten av alle OECD-landene, til tross for god befolkningshelse. Kjønnsforskjellen i sykefravær er relativt høyere i Norge (ca. 70% høyere hos kvinner enn hos menn) enn i andre OECD-land (cirka 50% høyere). 

Denne kjønnsforskjellen i sykefravær er en stor utfordring når det gjelder kvinnehelse, livskvalitet og likestilling mellom kjønnene. Årsakene til kjønnsforskjellene er i stor grad uforklarlig i forskningslitteraturen. Det finnes ingen evidensbasert klinisk intervensjon som kan redusere eller forhindre kjønnsforskjellen i sykefravær.

Vi vil bruke data fra to store multisenter randomisert kontrollerte prosjekt fra HelseIArbeid-klinikkene i Nord-Norge. Pasienters bakgrunn og videre forløp vil hentes i registerdata for sykefravær, sysselsetting, langsiktige fordeler, bruk av helsetjenester over en periode på 20 år. 

I arbeidspakke 1 (WP1) vil vi utforske seks hypoteser for høyere sykefraværsrater hos kvinner enn menn. Disse inkluderer kjønnsforskjeller i: 
1. spesifikke helseproblemer, inkludert symptomer og diagnoser, 
2. tanker om årsaker til helseproblem og konsekvenser for sykefravær, 
3. overbevisninger om helsebringende eller forebyggende effektene av sykefravær, 
4. opplevd arbeidsmiljø og utfordringer i mulige konflikter mellom arbeidsliv og privatliv, 
5. opplevde barrierer retur til arbeid fra sykmelding, 
6. ønsker, prioriteringer og forventninger til karriere og andre livsprioriteringer. 

Psykiske lidelser som angst og depresjon, samt muskel- og skjelettplager, er vanlige diagnoser for sykmelding, og vanligere blant kvinner enn menn, og et flertall av HelseIArbeid-pasientene er kvinner. I WP2 vil vi teste om en klinisk intervensjon for å forebygge sykefravær, og øke retur til arbeid blant sykmeldte, kan redusere kjønnsforskjellen i sykefravær. 

Vi vil gjennomføre systematiske litteraturoppsummeringer for begge arbeidspakkene i tidlig prosjektperiode.

Norwegian women have the highest sickness absence rate of all countries in the OECD, despite a good population health. The gender difference in sickness absence is relatively higher in Norway (70%) than in other OECD countries (50%), but the gender difference is observed in all economies where female labour force participation is high.

This gender difference represents a major concern in terms of health, wellbeing, and gender equality and is largely unexplained in the research literature. No intervention has yet proven to be efficacious in reducing this gender gap in sickness absence.

We will use data from two large multi-center RCTs on occupational health and return to work. To the best of our knowledge, these two RCTs constitute the largest within the field of work and health service delivery. The first RCT (n=1144) has successfully completed recruitment, and the second RCT (n=2500) will conclude recruitment during 2024. Patient data will be linked with high quality longitudinal register data from three different sources, containing data on employment, benefits, sickness absence and healthcare service utilisation covering a time span of 20 years.

In WP1, we will go beyond the state-of-the-art and explore three existing hypotheses with a novel angle, in addition to two original hypotheses for the relatively higher sickness absence rates in women compared to men. WP1 is based on secondary analyses of uniquely rich data from the RCTs. This level of detailed data have previously not been available for research on the gender difference in sickness absence.

In WP2, we will test the efficacy of a clinical intervention tailored to prevent sickness absence and promote return to work. Preliminary data indicates that there is high demand for this service in women, with a 70/30 split. This is as expected as the intervention targets those reporting symptoms of common mental disorders and/or musculoskeletal problems, conditions that are more prevalent in women than in men.

Explaining the gender difference in sickness absence and testing the efficacy of a clinical intervention to promote return to work in women

Preservation of grass silage for increased protein quality for dairy cows

Midlene fra NAERINGSPH-Nærings-phd fordelt på år

Midlene fra NAERINGSPH-Nærings-phd fordelt på fylker

Midlene fra NAERINGSPH-Nærings-phd fordelt på fagområde

Produktutvikler

The project are running according to planned activities. A feeding experiment has been carried out to study production responses using grass silage preserved with different types of silage additives. There is an ongoing work to compile the results from this experiment. At the same time, the next feeding experiment is planned, which will be carried out this winter. Comming experiment will focus on grass silage with different pre-drying and the harvesting of the experimental feed has gone as planned.

Protein fra grassurfôr utgjør hoveddelen av proteinforsyningen hos norske melkekyr. En økt utnytting av proteinet i grassurfôr vil redusere behovet for importert protein og sikre utnyttingen av norsk korn i rasjoner til drøvtyggere. Dette doktorgradsprosjektet har som hovedmål å bidra til en høyere proteinkvalitet på norsk grassurfôr og dermed øke proteinforsyningen fra norske fôrressurser i melkeproduksjonen. Arbeidet inngår i et større prosjekt, "Forage preservation for premium protein quality (EngProt)" som eies av NMBU. 

Tidligere forsøk har vist at fortørking og/eller bruk av ensileringsmiddel gir en mer restriktiv fermentering, noe som øker proteinverdien av surfôret. Responsen av den økte proteinverdien er derimot dårlig dokumentert i produksjonsforsøk. Doktorgradsprosjektet vil fokusere på å kartlegge effektene av restriktiv fermentering av grassurfôr, både på proteinutnytting i kuas stoffskifte og på melkeproduksjon i fôringsforsøk.

Hovedmålgruppen for prosjektet er norske husdyr- og grovfôrprodusenter. Om prosjektet blir vellykket vil det gi økt bærekraft for norsk produksjon av melk og kjøtt.

Konservering av grassurfôr for økt proteinkvalitet til melkekyr

For a number of years SINTEF Petroleum Research has been active in increasing the geologic understanding and improving exploration technology related to Arctic regions. Focus area for this research has been the Norwegian part of the Barents Sea. The goal of this research has been to increase the exploration success rate, reduce the potential environmental impact and to reduce finding costs in the area. 

A major risk factor for exploration in the Barents Sea is leakage of hydrocarbons from traps due to th e recent uplift and erosion. In the proposed project we will increase our understanding of the geological conditions and develop predictive methods of sealing and leakage, with the goal of increasing exploration success factors. 

Important topics for res earch are properties of the top seal, the recent burial and uplift history, and hydrocarbon leakage processes. Better understanding of the geologic processes, leading to improved target definitions, is important for finding new reserves in the region and thereby improving the business potential of the area. Better geologic knowledge will also reduce drilling risk and cost, and will reduce the number of dry wells. This also has positive environmental impact in reducing unneccesary drilling activity as well  as making drilling operations safer, which is important in an environmental sensitive area.

Top seal integrity and leakage, with relevance for exploration risk in the Barents Sea

The number of sour (H2S-containing) oil and gas fields worldwide is increasing, as sweet fields are being depleted and high oil prices vouch for profitable development of sour oil and gas finds. Sour oil and gas production and transport always imply a ris k of material damage and shutdowns due to CO2/H2S corrosion, and especially localised corrosion attacks. Development of these fields necessitates development of better, and more economical, corrosion control methods to prevent environmental hazards and pr oduction upsets caused by leaks and ruptures. 

Although a good understanding of the general corrosion mechanisms in sour environments has been developed, the mechanisms of localised corrosion attacks has yet to be satisfactorily explained. Thus, the obje ctive of the project will be to improve the understanding of localised CO2/H2S corrosion through experimental research and computer modelling. The advances in experimental methodology and modelling routines are expected to benefit research on other types localised corrosion as well.

The challenge of predicting localised CO2/H2S corrosion must be solved through improved understanding of the behaviour of iron sulfide corrosion films; their mechanical properties, galvanic interactions between protective fil ms and pits, precipitation and heterogeneous reactions. The project will produce thermodynamic and kinetic data that are required for localised corrosion prediction for the industry.

The knowledge gained will benefit the industry in design and operation of sour gas pipeline systems and other sour service facilities. This will be important for the Norwegian oil, service and supplier companies when they now are starting operations in other parts of the world with high amounts of H2S, and for international oil companies already operating in these areas.

The project will run for 3 years with a budget of 2.5 MNOK per year. A PhD or post-doc study will be included in the project.

Fundamental Understanding Of Localised Corrosion In H2s-Containing Environments

The Norwegian Continental Shelf (NCS) is facing considerable challenges with regards to cost, reserves, recovery and environment. IRIS in collaboration with UiS aims to take a leading position within drilling and well technology to meet some of these chal lenges.

Many applications for integrated operations, drilling and well operations and field developments within the oil industry require data from hydrocarbon bearing formations that reflect current knowledge at all times. The recently developed wired pi pe technology is expected to increase telemetry rates drastically, thus offering a continuous stream of subsurface information which must be efficiently managed. Real-time handling of reservoir information could potentially be accomplished by utilising an d integrating all available data and developing processes and models that can be maintained and dynamically modified/updated, to accommodate new information, throughout the life of an asset.

The project's goal is to develop methods for effective and dyna mic earth model management applying multi-resolution techniques. The proposed technology forms a basis for a long range of applications that require fast access to data from an always up-to-date earth model.
The proposed methodology will
- Allow fast and continuous updates of earth model data even for real-time applications that continuously receive streams of data.
- Enable efficient work processes as applications that require earth model data can work independently of each other.
- Enable more accurate and efficient handling of very large sets of data.
- Allow access to earth model data at any scale.
- Provide means for efficient transmission of large earth model data sets over computer networks, which is a strong requirement for applications utilised w ithin integrated operations.

The development and implementation of this dynamic methodology will pave the way for more informed, better designed and effective reservoir development plans and management.

Flexible Earth Model Management

Sustained well integrity is increasingly important to the petroleum industry operating on the Norwegian Continental Shelf. An increasing trend of well integrity failures with loss of pressure barriers is being reported on the NCS and internationally with both HSE risk and loss of production. Extended well life in mature areas, sub-sea wells and operations in Artic and environmental sensitive areas are key areas of concern. There is a need for accelerated research within this area.

The aim of this project  is to raise the Institute's fundamental scientific and integrated competence on critical issues related to structural well and wellbore integrity. The work packages encompass key scientific areas important to understand a very complex picture and to iden tify further R&D needs within the industry. In-depth studies and software modelling will be performed on key integrity failure mechanisms. Examples are well chemistry impact on mechanical well components (tubular/casing, packers, seals, cement degradation  etc), thermal and mechanical loads during start-up and changing well applications, and formation induced problems (shale instability, depleted reservoirs, sand production, subsalt etc). Other tasks will be on the impact of new trends related to more chal lenging well applications and operations (HPHT, CO2,  monobore wells, subsea well interventions etc) and to new technology being introduced (multilaterals, through tubing sidetracks, new materials, downhole equipment etc). For long term well integrity (Ar ctic, CO2 storage) and mature wells on NCS passing the design life, assessing the risk will be a focused activity.

Industry and authorities will be approached for data and experience exchange. Project results will be communicated through workshops and sc ientific publications. The potential value of managing well integrity is fewer well incidents through better design, improved well diagnostics tools and understanding of critical well operations.

Understanding and managing well integrity for mature and future well infrastructures

The project is a continuation of GeoScale (2004-2007), a strategic research project (grant no. 158908/I30) whose main objective was to develop a new technology for reservoir simulation of full-scale geological models on desktop computers.

The main object ive of GeoScale II is to continue the basic development of the `GeoScale technology' so that it becomes a super-fast simulation technology that can be used to simplify modeling work flows, speed up data integration optimization work flows, aid in interact ive planning, and improve management decisions. High relevance of the proposed research is ensured through the research group's portfolio of industry projects, through academic collaboration and participation in the Center for Integrated Operations in the  Petroleum Industry, a national center for research-based innovation at NTNU.  Moreover, industrial relations are designated as a separate work package with special emphasis on frequent contacts with software vendors and end-users in oil companies.

The p roposal attempts to close the knowledge gap between the current state of multiscale reservoir simulation and industry-standard solvers, and, in addition, extend the scope of multiscale simulation to applications where business decisions are made in real-t ime --- applications that can only take advantage of simulation tools capable of computing almost instant flow responses.

The total budget of the proposal is 9.0 million NOK over the three-year period 2008-2010. This level of basic funding will enable SI NTEF to advance the core of a technology that has many applications - but where each of the end users at this point in time will not bear the financial burden of a further development of this core. The project will also allow SINTEF to avoid having to par cel out IP rights thus hindering the development of a unified methodology.  Longer term, we believe the research will give great benefits to Norwegian industry and research.

GeoScale: Reservoir Simulation on a Geological Scale, Part II

Tracer technology is one of few methods which can provide direct dynamic information of the reservoir. It is simple and cheap in use, and can be adapted to all kinds of oil reservoirs. IFE is in the forefront of reservoir tracer technology development and  use. In the present project we will concentrate on development of industrial radiotracer generators for short-lived radionuclides and introduce a new concept in tracer technology for the petroleum industry: Nano-tracers. The main deliverables from the pr oject are:
a.	2-4 new laboratory-qualified radiotracer generator systems based on 2-4 different nuclear mother-daughter relationships that, with slight modifications may provide > 10 new short-lived radiotracers for near-well, well and process studies.
b. 	A novel type of tracer material based on nanoparticles, so-called nano-tracers, qualified on the laboratory scale. They may be applicable as tracers for oil or water flow in reservoir examinations. In combination with radiotracer generators, they will be  tracers for mass transport in process studies. Some variations of particles may be functionalized to enable tracing of system properties (pH, temperature, salinity etc.).
c.	A field tracer service based on off-line use of the radiotracer generators will be established.
d.	A knowledge base is established for these technologies and the combination of them which will enable further development of the techniques into automatically (remotely) operated monitoring devises for e-field operation.
e.	A knowledge b ase is established for potential upscaling of nano-tracer production and further research proposal applications within the Petromax program (KMB or BIP proposals) to qualify nano-tracers in field pilots in co-operation with oil companies.
f.	A unique comp etence is established on nano-tracers for application in the geosphere and in particular in oil reservoirs which will be the basis for a continued engagement and development in this new field.

New functional tracers based on nanotechnology and radiotracer generators

The proposed SIP will represent an important and considerable research effort with the main objective of developing a new seismic imaging system at NORSAR. Recorded or synthetic data will be input to the imaging system in order to generate target-oriented  depth images of the ground structures detected by elastic waves. The imaging or migration methods to be used and further developed, are ray tracing based, i.e., classified among Kirchhoff summation approaches, as opposed to wave-equation methods. Such Ki rchhoff methods need Green's functions (traveltimes, amplitudes, etc) to correct for wave propagation effects between all sources and receivers, and all points of the target zone to image. The key method to compute ray tracing based Green's functions will  be the 3D Wavefront Construction (WF3D) ray tracer developed by NORSAR since 1993 and now part of the commercial modelling package. WF3D is indeed used by the industry for imaging purposes. The existing WF3D tracer will therefore be adapted for a more ef ficient and flexible use in imaging, and interpolation techniques will be studied to allow coarser grids of Green's function. The on-going developments of WF3D towards complex anisotropy will also be a fundamental basis for imaging. Another class of metho ds to be used for Green's funtions are Eikonal solvers, to complete WF3D with first-arrivals. A second key element of ray tracing modelling is an adequate model. There is indeed a need for a more flexible type of model, including a new dimension, i.e., th e possibility to easily perturbe the model, which is important for integrating modelling, tomography and imaging, as all these steps are needed in a complete inversion approach. Efficient and modelling-based data access to large files on hard disks is als o a necessity for target-oriented imaging. At last, modelling by demigration will be studied too because such techniques are closely related to imaging and will significantly extend the modelling tools of NORSAR.

Flexible local seismic imaging in an integrated dynamic modelling framework

Subsea processing and transportation of multiphase fluids over long distances is becoming a viable solution for several subsea fields. Flow assurance is becoming an increasing challenge as depth and step out length are increasing. The processes conditions  with low temperatures have the potential to generate hydrates and deposition of wax and scale. This is a challenge that is being solved in different ways today: either by injecting chemicals like large amounts of glycol and/or new polymers that control c rystallisation and fatal plugging and improve flow. New and more reliable instrumentation needs to be developed in order to optimise the use of chemicals and monitor the status of the undesired components in the flow. 
                The proposed SIP pro poses a subsea pipeline measurement station combining various measurement techniques to enable early pre-warning detection of hydrate formation and measurement of wax/scale build-up and layer on the pipeline walls.  A main objective of the proposed R&D pr ogramme is to further improve CMR?s technology basis for development of new instruments and products for improved exploitation of oil and gas resources.  In particular, the programme will focus on multimodality technologies as a basis to realize such a me asurement station.
	In addition to the education of PhD and Master candidates, the SIP will lead to specific project results such as prototype instrument solutions. It is an intention that the SIP shall trigger activities and industrial projects as spin-o ffs to the SIP (in relation to the proposed SIP activities, or in addition to these), to be funded by other sources. The SIP will contribute to strengthen Norway not only as a leading supplier of oil and gas, but also as a supplier of advanced measurement  technology for controlled and safe use of the petroleum resources.

Multimodal flow assurance metering station (MuFAMES).

The proposed SIP will represent a considerable research effort with the main objective to develop a new modelling system for transforming 4D (time lapse) seismic data to reservoir model changes, which can improve the reliability of fluid simulation. The m odelling system will be integrated in an already established modelling framework called SeisRoX. The SeisRoX model contains physical properties for a number of rock layers in a petroleum reservoir zone, and these properties are classified in 3 different d omains: geologic domain (G= reservoir properties like porosity, permeability, lithology, oil/gas content), elastic domain (E= elastic properties like seismic velocities and density), and reflectivity domain (R= reflection properties of seismic waves). In the present forward version one can import a model (e. g. Eclipse) from a fluid simulation (F) at different time steps, and define G at each step. By forward modelling procedures one can do the transformation G->E->R, and from R calculate a seismic respon se (S). This forward procedure is e. g. used for predicting the 4D seismic differences for varying fluid scenarios (4D feasibility studies). The SIP focuses on the inverse work-flow, that is, S->R->E->G->F, aiming at modelling changes in the fluid paramet ers from observed differences in 4D seismic data. To be able to perform the above 'transformations' in a proper (unique) way, assumptions or constraints must be added at critical steps in the process. An important add-on functionality of the SeisRoX syste m is the possibility of perturbing the model parameters in any chosen domain, and calculate the implications in the other domains. This allows valuable sensitivity analysis at all stages of the modelling process within a unified and consistent framework.

From seismic data to reservoir changes - inversion approaches in 4D seismic modelling

The 3-year strategic research programme has four main focus areas: (1) Characterisation of geomaterials, including fault and fractures. (2) Wellbore stability and completion (3) Reservoir Monitoring (4) Instrumentation for underwater technology. Each issu e will be prioritized and developed over the three years based on recommendations from the Advisory Group. The following research topics have already been identified for 2006: 
(1) 1.1: Study of faults in field analogues, laboratory tests & determination of fault properties. 1.2: Consequence of clay smear and cataclasis on fault properties. 1.3: Seismic wave propagation in fractured rocks: novel 3D modelling & application to field examples. 1.4: Triaxial testing of geomaterials for high temperature and lo w permeability shales. 1.5: Interpretation of borehole logging from laboratory testing (resistivity, permeability & acoustic measurements) and particle modelling. 
(2) 2.1: Hydraulic fracturing in collapsible soft materials - investigation of fluid rock i nteraction processes occurring at crack tip. 2.2: Development of hollow cylinder tests at NGI - a pilot study. 
(3) 3.1 Effect of reservoir production on fracture seismic properties. Time-lapse seismic in fractured reservoirs.
(4) 4.1: Geotechnical / Geoh azards seabed vibrator - a pilot study. 4.2: EM pipe / cable tracker and pipeline plug detection - pilot study

These topics were selected after brainstorming at NGI on the priorities for research in Oil and Gas Exploration & Production sector. Results fr om the research programme will contribute to develop cost effective solutions, and increase the competitiveness and export of Norwegian technology in the Oil and Gas Sector. In addition, the strategic programme will involve one or several doctoral candida tes. The contact and co-operation between the universities and NGI are already well established. The research will involve preparation and presentation of journal and conference papers & popular articles.

Integrated Petroleum Reservoir Geomechanics and Geophysics

Liquid accumulation due to velocity difference between gas and liquids has a significant influence on the capacity and operability of a multiphase hydrocarbon production system. Droplet transport increases the liquid transport and thereby reduces the liqu id accumulation. Present models for droplet transport are based on experiments at conditions far from actual large diameter high pressure condensate lines. The theoretical basis seems poor.  Attempts at applying better phenomenological models for droplet distribution to low velocity dense gas experimental data has not been as succesfull as when applied to low gas density - high velocity experiments. Therefore the scaling properties of the models are suspect. The reason is probably a too simplistic descrip tion of the turbulence, which probably are not satisfying with a large assymetry in the distribution of liquid surface roughness around the pipe wall.

The program will study the turbulence in a gas flowing over a wavy liquid surface using Particle Image Velocimetry (PIV).  University of OSLO (UiO) will contribute with measurement hardware and software, assist with experiements, and perform the data analysis. 

Based on existing models for stratified flow a model describing the observed turbulence distrib ution will be developed.

A model for droplet dispersion that can take into account the spatial distribution of turbulence will be developed and coupled to the stratified flow model.

It would be highly desirable to increase the production of droplets, an d to produce smaller droplets that are more easily carried by the gas flow. Similar technologies used in other fields of application like agricultural spraying and liquid-liquid extraction by static  electricity will be studied for potential transfer of t echnology.

NAERINGSPH-Nærings-phd

Konservering av grassurfôr for økt proteinkvalitet til melkekyr

Alternative title: Preservation of grass silage for increased protein quality for dairy cows

Awarded: NOK 1.8 mill.

Popular Science Description

Achieved effects

Summary

Funding scheme:

NAERINGSPH-Nærings-phd

Funding Sources

Thematic Areas and Topics