| 1. |
- Fernandez, J. L. Abelleira, et al.
(författare)
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A Large Hadron Electron Collider at CERN
- 2012
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Skarpengland, T, et al.
(författare)
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Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28337-
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage.
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| 4. |
- Yeo, Leonard L L, et al.
(författare)
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Nongated Cardiac Computed Tomographic Angiograms for Detection of Embolic Sources in Acute Ischemic Stroke
- 2017
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 48:5, s. 1256-1261
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: axis coverage of a non-ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose.METHODS: Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3-4 mL/s; total 60-80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours.RESULTS: Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88-4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV).CONCLUSIONS: Including the heart and ascending aorta in a routine non-ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients.
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| 5. |
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| 6. |
- Eide, W. M., et al.
(författare)
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FIRST-YEAR nursing students’ experiences of simulation involving care of older patients : A descriptive and exploratory study
- 2020
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Ingår i: Nurse Education in Practice. - : Elsevier. - 1471-5953 .- 1873-5223. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Mastering geriatric nursing skills takes time and its acquisition should start early in undergraduate nursing training. The purpose of this study is to synthesise and evaluate the learning experiences that first-year nursing students had following geriatric patient simulation and practice of clinical patient handover. Qualitative content analysis of survey comments from first-year students (n = 216) at a large university in Norway were performed. Simulation training included systematic patient observation of scenarios based on genuine geriatric cases in nursing homes and practice of clinical patient handover. Content analyses identified four generic categories: (1) ‘embodying theoretical knowledge’; (2) ‘increased awareness about one's self’; (3) ‘understanding that collaboration is needed’; (4) ‘preparing for future work life’. These themes provide evidence for students integrating geriatric theoretical knowledge with clinical skills as a result of simulation. Analysis of learning experiences shows that geriatric scenario simulation and practice of clinical patient handover are valuable instruments before entering clinical training with geriatric patients, even for novice students. The use of genuine simulation cases and instruction on the use of clinical handover instruments are effective in producing conceptual changes that prepare students for their first encounter with complex, real-world geriatric scenarios.
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| 7. |
- Fenstad, M H, et al.
(författare)
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STOX2 but not STOX1 is differentially expressed in decidua from pre-eclamptic women : data from the Second Nord-Trondelag Health Study
- 2010
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 16:12, s. 960-968
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Tidskriftsartikel (refereegranskat)abstract
- Variation in the Storkhead box-1 (STOX1) gene has previously been associated with pre-eclampsia. In this study, we assess candidate single nucleotide polymorphisms (SNPs) in STOX1 in an independent population cohort of pre-eclamptic (n = 1.139) and non-pre-eclamptic (n = 2.269) women (the HUNT2 study). We also compare gene expression levels of STOX1 and its paralogue, Storkhead box-2 (STOX2) in decidual tissue from pregnancies complicated by pre-eclampsia and/or fetal growth restriction (FGR) (n = 40) to expression levels in decidual tissue from uncomplicated pregnancies (n = 59). We cannot confirm association of the candidate SNPs to pre-eclampsia (P > 0.05). For STOX1, no differential gene expression was observed in any of the case groups, whereas STOX2 showed significantly lower expression in deciduas from pregnancies complicated by both pre-eclampsia and FGR as compared with controls (P = 0.01). We further report a strong correlation between transcriptional alterations reported previously in choriocarcinoma cells over expressing STOX1A and alterations observed in decidual tissue of pre-eclamptic women with FGR.
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| 8. |
- Zabriskie, Matthew S., et al.
(författare)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Amofah, H. A., et al.
(författare)
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Factors affecting in-hospital sleep-wake pattern in octogenarians during the early postoperative phase after transcutaneous aortic valve replacement
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S53-S53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Octogenarian patients are an increasing group admitted for advanced cardiac treatment. Little is known about factors disturbing their sleep-wake pattern in the early postoperative phase after transcutaneous aortic valve replacement (TAVI), as current knowledge is based upon studies on younger age groups treated for surgical aortic valve replacement.Aim: To determine factors affecting the in-hospital sleep wake pattern in octogenarian patients after TAVI.Methods: This is a prospective cohort study in a tertiary university hospital. Inclusion criteria were age > 80 years with severe aortic stenosis accepted for TAVI. Actigraphy was used to identify sleep-wake pattern (sleep time night and sleep time day), and the Minimal Insomnia Symptom Scale (MISS) to measure self-reported insomnia daily during the first five postoperative days. Charlson`s comorbidity index was used as a measure of comorbidities and the Visual Analog Scale (VAS) to rate pain severity. Information regarding duration of anesthesia, blood transfusion and parenteral administration of morphine equivalents were derived from the patients’ medical journals. Multiple regression analysis was used to test associations between variables.Results: In all, 65 patients (41 women) were included. Mean age was 85 years (SD 2.8). No significant associations were found between age, comorbidities, blood transfusion and morphine equivalents and sleep. Gender was significantly associated with sleep time night and sleep efficiency as men had shortest duration of sleep from the third to the fifth postoperative night (p < .001, and adjusted R2=.230 to .283). Duration of anesthesia had a significant association with sleep time night and sleep efficiency from the third to the fifth postoperative night (p=.013 to p < .001, and adjusted R2=.230 to .283), where longer duration gave less total sleep and lower sleep efficiency. VAS score correlated with wake time night the third night, where a higher VAS score gave more wake time (p=.006 and adjusted R2 .236).Conclusion: Male gender, longer duration of perioperative anesthesia and postoperative pain were associated with disturbances in the postoperative sleep-wake pattern in octogenarian patients in the early postoperative phase after TAVI. This knowledge is important and relevant and should have implications in improving patient care.
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| 13. |
- Amofah, H. A., et al.
(författare)
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Factors associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after surgical aortic valve replacement
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S63-S64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disturbances of the sleep-wake pattern are known phenomenon in the postoperative phase after aortic valve replacement (SAVR) that have negative impact on the morbidity, quality of life and mortality. Octogenarian patients are an increasing group admitted for cardiac surgery, however knowledge is based on younger patients.Aims: To determine factors associated with disturbances in postoperative sleep-wake pattern in octogenarian patients after SAVR.Methods: A prospective cohort study of octogenarian patients in a single center university hospital. Inclusion criteria were age > 80 years, severe aortic stenosis, accepted for SAVR. Actigraphy was used to identify the sleep-wake pattern (sleep-time, sleep efficiency and wake time night and sleep- and wake-time day) for the five first postoperative days, and the sleep questionnaires Minimal Insomnia Symptom scale (MISS) to measure the selfreported insomnia at baseline and daily for the five first postoperative days. Charlsons comorbidity index was used to score comorbidities and the Visual Analog Scale (VAS), was used to rate pain severity. The patients’ medical journals were used to record duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusions and parenteral administration of morphine equivalents. Multiple regression analysis was used to test associations between variables.Results: In all, 78 patients were included (40 women). Mean age was 82 years (SD 2.0). For the sleep-wake pattern first to fifth postoperative night, mean sleep-time night was 330-370 minutes (SD 32-124). Mean sleep efficiency was 68-77% (SD 21-26). Mean sleep-time day was 545-712 minutes (SD 146-169). Mean insomnia score was 1,8-5,3 (SD 2,6-3,8). On the first postoperative night the pain VAS score correlated with wake time night, where a higher VAS indicated more wake time (p=.014, adjusted R2=.213). No other variable; age, gender, duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusion or morphine equivalents showed significant association with the sleep-wake pattern or insomnia.Conclusion: Postoperative pain was associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after SAVR. This indicates that pain management may be inadequate for patients after SAVR. More research on this issue is needed to establish data needed to improve treatment and care.
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| 14. |
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| 15. |
- Eide, L. S. P., et al.
(författare)
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Urinary catheter use and delirium after aortic valve therapy
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S3-S4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Indwelling urinary catheters (IUC) are valuable devices that help to control and monitor urine output under and after invasive procedures. However, adverse outcomes might arise following use of IUC, and several studies show that IUC can be a risk factor for postoperative delirium. Delirium is an acute and fluctuating change in attention and cognition that might lead to extended hospital stay, and more morbidity and mortality. The association between delirium and the duration of IUC use in octogenarians after Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Implantation (TAVI) remains to be established.Purpose: To determine if the duration of IUC use after SAVR or TAVI predicts the development of delirium in older people.Methods: This is a prospective cohort study of octogenarian patients (N=136) in a tertiary university hospital. Inclusion criteria: ⩾80 years, severe aortic stenosis, and elective TAVI or SAVR. Exclusion criteria: Inability to speak Norwegian or declined consent to participate in the study. The Mini-Mental State examination was used to evaluate global cognitive function at baseline. The Confusion Assessment Method allowed the identification of delirium during five postoperative days. The duration of IUC use was collected from patients’ medical records. The predictive effect of IUC in the development of delirium was examined using multiple regression.Results: The majority (57%) of patients was female, and 46% received TAVI. Patients in the TAVI group were older (85 vs. 82 years-old, P<0.001), had more comorbidities (2.5 vs.1.8, P=0.001) and higher logistic EuroSCORE (19.6 vs. 9.4,P<0.001). Delirium was present in 66% of patients treated with SAVR vs. 44% of those receiving TAVI. The average duration of IUC use in SAVR patients with delirium was 66 hours (SD=29) compared to 59 hours (SD=27) in those without delirium (P=0.307), and in TAVI patients with delirium was 58 hours (SD=38) compared to 32 hours (SD=15) for those without delirium (P=0.001). Multivariate regression analysis shows that lower cognitive function (P=0.040), type of aortic valve treatment (P=0.043) and longer of IUC use (P=0.002) predicted the development of delirium.Conclusion: In octogenarian patients undergoing aortic valve treatment, the duration of IUC use can predict delirium. Further research is needed to mitigate the risks of delirium in patients undergoing aortic valve treatment.
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| 16. |
- Eide, P. K., et al.
(författare)
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Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-beta (A beta 40 and A beta 42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function. Plasma neurodegeneration biomarkers are increasingly utilized to predict neurological disease. Here, authors show in different neurological disorders associations between plasma neurodegeneration biomarker concentrations and various measures of glymphatic and meningeal lymphatic functions.
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| 17. |
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| 18. |
- Frantzen, Astri Tafjord, et al.
(författare)
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Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement
- 2021
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Ingår i: Heart, Lung and Circulation. - : Elsevier. - 1443-9506 .- 1444-2892. ; 30:8, s. 1221-1231
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFrailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care.AimWe aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR.MethodIn a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated.ResultsData were available for 143 consecutive patients (mean age 83 +/- 2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002).ConclusionsAdvanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.
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| 19. |
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| 20. |
- Hjern, Anders, et al.
(författare)
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Unaccompanied Refugee Minors: A Comparative Study in Norway and Sweden
- 2020
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Ingår i: Coming of Age in Exile. Health and Socio-Economic inequalities in Young Refugees in the Nordic Welfare Societies. - Copenhagen : University of Copenhagen, Department of Public Health. - 9788797277904 ; , s. 89-99
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Hvoslef-Eide, M., et al.
(författare)
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The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia
- 2015
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:21-22, s. 3853-3872
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Forskningsöversikt (refereegranskat)abstract
- The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.
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| 22. |
- Jebsen, Nina L., et al.
(författare)
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Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall
- 2013
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 86:5, s. 949-955
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose-response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma. (C) 2013 Elsevier Inc.
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| 23. |
- Johansson, Åsa, et al.
(författare)
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Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:7, s. 796-800
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess lipid traits as risk factors for PE and CVD by whole genome transcriptional profiling performed on Norwegian decidua basalis tissues (N=95) from preeclamptic and normal pregnancies and on blood lymphocytes (N=1240) from the San Antonio Family Heart Study (SAFHS). Among 222 genes that were differentially expressed (false discovery rate (FDR) P-value < 0.05) between the PE, cases and controls, we found one gene, ACOX2 (acyl-coenzyme A oxidase 2, branched chain), that was downregulated in PE whose transcription was also inversely correlated with triglyceride levels (P=5.6 x 10(-7); FDR P-value=0.0002) in SAFHS. We further report associations between SNPs in the ACOX2 gene and the transcription level (P-value=0.0045) of the gene, as well as with triglyceride levels (P-value=0.0051). ACOX2 is involved in bile acid production, a process that has been associated with both oxidative stress and regulation of triglyceride levels. Oxidative stress and increased triglyceride levels are known risk factors for CVD and both have also been associated with PE. Our results suggest that downregulation of ACOX2 is a shared risk factor for PE and CVD.
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| 24. |
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| 25. |
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| 26. |
- Kosibaty, Z, et al.
(författare)
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Ras-Related Protein Rab-32 and Thrombospondin 1 Confer Resistance to the EGFR Tyrosine Kinase Inhibitor Osimertinib by Activating Focal Adhesion Kinase in Non-Small Cell Lung Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:14
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with the tyrosine kinase inhibitor (TKI) osimertinib is the standard of care for non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR). Osimertinib is also used in T790M-positive NSCLC that may occur de novo or be acquired following first-line treatment with other EGFR TKIs (i.e., gefitinib, erlotinib, afatinib, or dacomitinib). However, patients treated with osimertinib have a high risk of developing resistance to the treatment. A substantial fraction of the mechanisms for resistance is unknown and may involve RNA and/or protein alterations. In this study, we investigated the full transcriptome of parental and osimertinib-resistant cell lines, revealing 131 differentially expressed genes. Knockdown screening of the genes upregulated in resistant cell lines uncovered eight genes to partly confer resistance to osimertinib. Among them, we detected the expression of Ras-related protein Rab-32 (RAB32) and thrombospondin 1 (THBS1) in plasmas sampled at baseline and at disease progression from EGFR-positive NSCLC patients treated with osimertinib. Both genes were upregulated in progression samples. Moreover, we found that knockdown of RAB32 and THBS1 reduced the expression of phosphorylated focal adhesion kinase (FAK). Combination of osimertinib with a FAK inhibitor resulted in synergistic toxicity in osimertinib-resistant cells, suggesting a potential therapeutic drug combination for overcoming resistance to osimertinib in NSCLC patients.
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| 27. |
- Larm, Malin, et al.
(författare)
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Fecal glucocorticoid metabolites as an indicator of adrenocortical activity in Arctic foxes (Vulpes lagopus) and recommendations for future studies
- 2021
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Ingår i: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 44:10, s. 1925-1937
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Tidskriftsartikel (refereegranskat)abstract
- Measuring fecal glucocorticoid metabolites (fGCMs) is a widely used, non-invasive method for studies of stress in vertebrates. To study physiological responses in wild Arctic foxes (Vulpes lagopus) to perceived stressors such as fluctuating food availability, occurrence of competitors and predators and disturbance from human activities, a species-specific physiological validation of a method to evaluate adrenocortical activity is needed. Here we used 15 captive Arctic foxes (both males and females and juveniles and adults) to investigate fGCM concentrations following ACTH injection (physiological validation), or handling alone and compared them with their respective baseline concentrations prior to the treatments. A 5 alpha-pregnane-3ss,11ss,21-triol-20-one enzyme immunoassay measured significant fGCM increases following both treatments. The time lags to reach peak fGCM values were 9.3 +/- 1.3 h and 12.8 +/- 1.7 h for ACTH and handling treatment, respectively. Concentrations of fGCMs varied a lot between individuals, but not attributed to sex nor age of the foxes. However, we found a negative relationship between boldness and fGCM concentrations. Faecal glucocorticoid metabolites concentrations did not change significantly over a period of 48 h in samples kept at temperatures reflecting winter and summer means. This would allow the collection of samples up to two days old in the wild regardless of the season. We conclude that our successfully validated method for measuring fGCMs can be used as a non-invasive tool for studies exploring various stressors both in wild and captive Arctic foxes.
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| 30. |
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| 31. |
- Swolin-Eide, Diana, 1968, et al.
(författare)
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Affected skeletal growth but normal bone mineralization in rat offspring after prenatal dexamethasone exposure.
- 2002
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 174:3, s. 411-8
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Tidskriftsartikel (refereegranskat)abstract
- Events occurring early in life or prenatally are able to play important roles in the pathogenesis of diseases in adult life. Different sorts of stress or hormonal influences, during particular periods of pregnancy, may result in persisting or transient changes in physiology. Glucocorticoids are used for the treatment of a variety of diseases, to promote organ maturation and to prevent preterm delivery. Glucocorticoids are also known to affect skeletal growth and adult bone metabolism. The aim of the present study was to investigate whether exposure to dexamethasone (Dex) during fetal life has any effect on skeletal growth and/or bone mineral density in adult rat offspring. Pregnant rats were given injections of either Dex (100 micro g/kg) or vehicle on days 9, 11 and 13 of gestation. Dex-exposed male but not female rat offspring showed transient increases in crown-rump length and tibia and femur lengths at 3-6 weeks of age. In contrast, the cortical bone dimensions were altered in 12-week-old female but not male Dex-exposed offspring. The areal bone mineral densities of the long bones and the spine, as determined by dual X-ray absorptiometry, and trabecular as well as cortical volumetric bone mineral density, as measured using peripheral quantitative computerized tomography, were unchanged in both male and female Dex-exposed offspring. In conclusion, prenatal Dex exposure affects skeletal growth in a gender-specific manner, while the mineralization of bones is unaffected in both male and female offspring.
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| 32. |
- Taule, T., et al.
(författare)
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Norwegian version of the Edinburgh cognitive and behavioural ALS screen: Construct validity, internal consistency, inter-rater, and test-retest reliability
- 2023
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Ingår i: Plos One. - 1932-6203. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundResearch collaboration highlight a need for validated tests in other languages than English. Translation and culture adjustments may threaten essential features of the original instrument. ObjectiveTo assess the internal consistency, inter-rater and test-retest reliability, and construct validity of the Norwegian version of the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS-N). MethodsPerformance of 71 subjects with ALS, 85 healthy controls (HC) and 6 controls with Alzheimer's disease (AD) were assessed with the ECAS-N. Test-retest interval was four months. Internal consistency was evaluated using Cronbach's alpha; reliability was assessed using intraclass correlation coefficient (ICC), Cohen's kappa, and Bland Altman plot. Five hypothesis, including the Montreal Cognitive Assessment (MoCA) screen, was evaluated for construct validity. ResultsECAS-N total score produced a Cronbach's alpha of 0.65, had excellent inter-rater reliability (ICC = 0.99) and acceptable test-retest reliability (ICC = 0.73). Construct validity analysis suggested valid use of the ECAS-N to distinguish people with ALS-specific cognitive impairment from HC (p = 0.001) and those with AD (p = 0.002). The MoCA and ECAS-N were moderately correlated (r = 0.53). ConclusionThe ECAS-N has potential to be used by different testers in clinical practice and research to screen patients with ALS who speak Norwegian and for documenting cognitive impairment over time.
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- Trovik, Linn H., et al.
(författare)
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Adjuvant radiotherapy in retroperitoneal sarcomas. A Scandinavian Sarcoma Group study of 97 patients
- 2014
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Ingår i: Acta Oncologica. - 1651-226X. ; 53:9, s. 1165-1172
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Tidskriftsartikel (refereegranskat)abstract
- Background. Currently there is no consensus on the use of adjuvant radiotherapy (RT) in retroperitoneal sarcoma (RPS). We have analysed clinical outcomes in patients with localised RPS treated at two Scandinavian Sarcoma Group (SSG) centres: Haukeland University Hospital (HUH), Bergen, Norway and Skane University Hospital (SUH), Lund, Sweden to clarify the effects of adjuvant RT on local control and overall survival (OS). Material and methods. Local databases and registers at HUH and SUH as well as the SSG central register were used to identify RPS patients. Patients with localised RPS who underwent surgery in Bergen between 1988 and 2009 and in Lund from 1998 to 2009 were included. Medical records were examined for clinical data, tumour characteristics, treatment factors and follow-up status. Archived tumour sections and tumour tissue were reviewed, and when necessary, restained and reclassified. Cox regression was used to analyse the association of potential prognostic factors with local recurrence-free survival (LRFS), metastasis-free survival (MFS) and OS. Results. The study included 97 patients: 52 from Norway and 45 from Sweden. The proportion of high-grade tumours was 73%. The five-year LRFS, MFS and OS were 55%, 59% and 60%, respectively. RT was significantly associated with improved local control resulting in a five-year LRFS of 77% compared with 39% without (p < 0.001). Furthermore, five-year OS was 71% in the RT group in contrast to 52% with surgery alone (p = 0.019). In the adjusted analysis RT proved to be a significant factor also for MFS (HR = 0.42, 95% CI 0.20-0.88, p = 0.021). In addition, high-grade malignancy, large tumour and positive surgical margin were risk factors for local recurrence. High malignancy grade was the only significant adverse prognostic factor for metastasis. High age and high-grade malignancy were negative prognostic factors for OS. Conclusion. Adjuvant RT was significantly associated with an improved five-year LRFS and OS.
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