Implementering av pasientbrev for nedtrapping og seponering av benzodiazepiner og benzodiazepinliknende preparater : ved Gågata legesenter

Benzodiazepiner og benzodiazepinliknende preparater (BoBLP) er de mest brukte legemidlene mot angst og søvnforstyrrelser, og medfører et betydelig misbrukspotensial samt risiko for toleranseutvikling. Avhengighet kan oppstå etter 2-4 ukers bruk innenfor terapeutiske doser. Seponering etter jevnlig bruk kan til tider gi alvorlige abstinenssymptomer. På tross av at nasjonale og internasjonale retningslinjer anbefaler korttidsbruk av BoBLP, er langtidsbruk fortsatt et utbredt fenomen. Vi ønsker i denne oppgaven å kartlegge effektive tiltak for å redusere langtidsbruk av BoBLP, og på bakgrunn av dette skissere et forbedringsprosjekt for en allmennpraksis. I eksisterende litteratur ble hovedsakelig to intervensjoner identifisert; (1) minimal intervensjon; for eksempel å gi enkle råd i form av brev, og (2) systematisk nedtrapping; behandlingsprogrammer ledet av lege eller psykolog. Det er evidens for effekt av begge de identifiserte intervensjonene. Vi valgte minimal intervensjon med utsending av brev som hovedtiltak i vårt forbedringsprosjekt. Forbedringsarbeidet går ut på å skissere et opplegg for å implementere bruk av informasjons- og motivasjonsbrev for å initiere nedtrapping og seponering av BOBLP, samt oppfordre til timebestilling for evalueringssamtale. Tiltaket skal implementeres ved hjelp av informasjonsskriv og kollegabasert terapiveiledning for de involverte allmennlegene. Vi ser for oss en prøveperiode på 6 måneder før vi, basert på våre indikatorer, evaluerer tiltaket. Vi konkluderer med at det er behov for et slikt tiltak, og at de foreslåtte intervensjonene er rimelige, lite arbeidskrevende og effektive

Kulturmøte i museal tekstilsamling. Et innblikk i kvinneliv og -virke på Sunnmøre ca. 1800 til tidlig 1900‐tall

Summary In my thesis, I write about cultural meeting in the Sunnmøre Museum textile collection, and women’s life and work in the Sunnmøre region ca. 1800 to early 20th-century. I have searched for traces of cultural meetings in the material, by using a micro-history-perspective and Ragnar Pedersen’s form-and-function method called “The scythe”. I have registered and analyzed 22 garments from the museum to find out if a cultural meeting has taken place. Has Danish and European fashion influenced how the garments look like, and what they are made of? Which traces are to be found in the fabric and cut? Where do the traces come from? Are various social groups represented in the material, and does the garments display inequalities on the basis of social status? What other cultural meetings turn out in the material? The answers give a glimpse of women’s life and work in the Sunnmøre region in the 19th century, where especially cotton and the sewing machine turns out to be cultural meeting phenomenon. With The scythe-method I have split up the material in features in a hierarchy, to find different degrees of norms trough a descriptive presentation of the garments and an analysis of the presented material. In conclusion, I find that there are several cultural meetings in the material, as well as the transition from traditional to fashion costume in the Sunnmøre region

High Expression of the Costimulatory Checkpoint Factor DNAM-1 by CD4+ T-Cells from Multiple Myeloma Patients Refractory to Daratumumab-Containing Regimens

Multiple myeloma is an incurable disease characterized by unregulated growth of malignant plasma cells in the bone marrow (BM). Tumor-induced dysfunction of T-cells may be responsible for immune evasion and failure of immunotherapy. Therefore, a better understanding of the phenotype of T-cells at the tumor site is needed. We assessed the expression of immune regulatory receptors on T-cell subsets from peripheral blood (PB) and BM using multicolor flow cytometry. Paired PB and BM samples were collected from newly diagnosed, treatment-naïve myeloma patients (n = 19) and patients progressing during treatment with the CD38 monoclonal antibody daratumumab alone or in combination with other anti-myeloma drugs (n = 39). We observed that CD4 + T-cells from both PB and BM of patients relapsing on daratumumab have a higher expression of the costimulatory checkpoint receptor DNAM-1. The potential role of DNAM-1 +CD4 + T-cells in the development of resistance to daratumumab needs further exploration. We also observed that the inhibitory checkpoint receptor TIGIT is more frequently expressed by BM CD8 + T-cells from myeloma patients than PD-1 and CTLA-4, which supports the hypothesis that TIGIT may play a central role in the immune escape of the malignant plasma cells. </p

Prisforholdet mellom å leie leilighet og å kjøpe leilighet i Oslo

Masteroppgave økonomi og administrasjon BE501 - Universitetet i Agder 2018Hensikten med denne oppgaven er å undersøke forholdet mellom leiepris og omsetningspris for leiligheter i Oslo. Internasjonalt har det blitt gjennomført flere studier av slike forholdstall i andre land og byer, men få er gjennomført med data fra det norske boligmarkedet. Vi behandler data fra to separate markeder, herunder markedet for solgte boliger og markedet for utleieboliger. Disse refererer vi til som henholdsvis eiermarkedet og leiemarkedet. DiPasquale og Wheaton sin 4-kvadrant-modell er det mest sentrale teoretiske grunnlaget for oppgaven. Modellen er en langsiktig likevektsmodell som kobler markedet for bruk av boligareal med eiermarkedet for eiendom, som gjør den relevant for oppgaven. Vi tar utgangspunkt i den hedonistiske pristeorien ved estimering av prisfunksjoner. I tillegg inkluderer vi Alonso-Muth-Mills-modellen om lokalisering, og Georg Akerlofs teori “Marked for Lemons”. Disse komplimenterer drøftingen av funnene i analysen. I analysen benytter vi 2538 observasjoner for eiermarkedet fra Eiendomsverdi, og 306 observasjoner for leiemarkedet fra Finn.no, i tidsperioden januar og februar 2018. Informasjonen som var vesentlig å samle inn var omsetningspris, fellesgjeld, primærromstørrelse og beliggenhet for de solgte boligene, og månedsleie, primærromstørrelse og beliggenhet for utleieboligene. Bydelene i Oslo brukes som beliggenhetsindikator. Vi definerer en ny avhengig variabel for eiermarkedet som vi kaller totalpris. Denne består av omsetningsprisen og en andel av fellesgjelden knyttet til boligen. Vi benytter to metoder ved beregning av forholdstall. Den første metoden baserer seg på estimert leiepris og estimert totalpris. Vi benytter her semilogaritmisk funksjonsform, ettersom denne passet best for våre data. Den andre metoden baserer seg på faktiske priser i markedet. Med utgangspunkt i observasjonene i leiemarkedet forsøkte vi å finne en likest mulig solgt bolig, basert på beliggenhet og størrelse. Bruk av to ulike metoder gir et bedre grunnlag for tolkning av boligmarkedet i Oslo. Våre resultater viser at det ikke foreligger et helt fast forhold mellom leiepris og totalpris i Oslo i tidsperioden. Vi finner derimot at forholdet mellom leiepris og totalpris varierer med beliggenhet. Videre finner vi en svak tendens til at forholdet varierer med primærromstørrels

Voldsutsatt ungdom i Norge - resultater fra helseundersøkelser i seks fylker

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Effekt av styrketrening på fysisk funksjon hos slagrammede med hemiparese

Formålet med dette litteraturstudiet er å undersøke om styrketrening har en positiv effekt på slagrammede med hemiparese. Litteraturstudiet inkluderte 8 studier som ble funnet gjennom et litteratursøk i PubMed og ScienceDirect. Studiene måtte være randomiserte kontrollerte studier (RCT) og måtte inkludere én eller flere tester som evaluerte fysisk funksjon. De inkluderte studiene så på hvorvidt styrketrening med motstand kunne bedre slagpasienters fysiske funksjon. Resultatene fra studiene viser at 6 av studiene hadde statistisk signifikant forbedring i fysisk funksjon. For de resterende 2 studiene var det også en forbedring i fysisk funksjon. Basert på resultatene fra de 8 inkluderte studiene vil man kunne si at styrketrening har en positiv effekt på fysisk funksjon hos slagrammede med hemiparese.The purpose of this literature study is to examine if resistance training has a positive effect on physical function for stroke patients with hemiparesis. The literature study included 8 studies that were found through a literature search in PubMed and ScienceDirect. The studies had to be randomized controlled studies (RCT) and had to include one or more tests that evaluated physical function. The included studies looked at whether strength training with resistance could improve stroke patients` physical function. The results from the studies show that 6 of the studies had a statistically significant improvement in physical function. For the remaining 2 studies, there was also an improvement in physical function. Based on the results from the 8 included studies, one can say that resistance training has a positive effect on physical function on stroke patients with hemiparesis

Detection of internal N7-methylguanosine (m⁷G) RNA modifications by mutational profiling sequencing

Methylation of guanosine on position N7 (m7G) on internal RNA positions has been found in all domains of life and have been implicated in human disease. Here, we present m7G Mutational Profiling sequencing (m7G-MaP-seq), which allows high throughput detection of m7G modifications at nucleotide resolution. In our method, m7G modified positions are converted to abasic sites by reduction with sodium borohydride, directly recorded as cDNA mutations through reverse transcription and sequenced. We detect positions with increased mutation rates in the reduced and control samples taking the possibility of sequencing/alignment error into account and use replicates to calculate statistical significance based on log likelihood ratio tests. We show that m7G-MaP-seq efficiently detects known m7G modifications in rRNA with mutational rates up to 25% and we map a previously uncharacterised evolutionarily conserved rRNA modification at position 1581 in Arabidopsis thaliana SSU rRNA. Furthermore, we identify m7G modifications in budding yeast, human and arabidopsis tRNAs and demonstrate that m7G modification occurs before tRNA splicing. We do not find any evidence for internal m7G modifications being present in other small RNA, such as miRNA, snoRNA and sRNA, including human Let-7e. Likewise, high sequencing depth m7G-MaP-seq analysis of mRNA from E. coli or yeast cells did not identify any internal m7G modifications.</p

Metabolomics identifies placental dysfunction and confirms Flt-1 (FMS-like tyrosine kinase receptor 1) biomarker specificity

Clinical end-stage parameters define the pregnancy disorders preeclampsia and fetal growth restriction while classification of the underlying placental dysfunction is missing and urgently needed. Flt-1 (FMS-like tyrosine kinase receptor 1) is the most promising placenta-derived predictive biomarker for preeclampsia. We aimed to classify placental dysfunction in preeclampsia and fetal growth restriction at delivery by metabolic profiling and authenticate the biomarker Flt-1 for placental dysfunction. We studied 143 pregnancies with or without preeclampsia and/or fetal growth restriction delivered by cesarean section. Metabolic placenta profiles were created by high-resolution magic angle spinning nuclear magnetic resonance spectroscopy and the resulting placental phenotypes obtained by hierarchical clustering. Placental Flt-1 expression (membrane-bound and soluble isoforms combined) and maternal serum Flt-1 expression (soluble isoforms) were analyzed by immunohistochemistry and ELISA, respectively. We identified 3 distinct placenta groups by 21 metabolites and diagnostic outcome parameters; normal placentas, moderate placental dysfunction, and severe placental dysfunction. Increased placental Flt-1 was associated with severe placental dysfunction, and increased serum Flt-1 was associated with moderate and severe placental dysfunction. The preeclamptic pregnancies with and without placental dysfunction could be distinguished by 5 metabolites and placental Flt-1. Placental Flt-1 alone could separate normal pregnancies with and without placental dysfunction. In conclusion, metabolomics could classify placental dysfunction and provide information not identified by traditional diagnostics and metabolites with biomarker potential were identified. Flt-1 was confirmed as precision biomarker for placental dysfunction, substantiating its usefulness for identification of high-risk pregnancies for preeclampsia and fetal growth restriction with placental involvement.acceptedVersio

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

Introduction Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2–7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking. Methods Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. Results Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. Discussion HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease.acceptedVersio

Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins

High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.publishedVersio