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  • Östling, Jörgen, et al. (författare)
  • IL-17-high asthma with features of a psoriasis immunophenotype
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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  • Alahmadi, Fahad, et al. (författare)
  • Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Rates of sub-optimal adherence to medications in asthma range up to 70%; the impact in severe asthma is likely to be particularly high. We measured self-reported adherence in participants in the U-BIOPRED cohort prescribed daily prednisolone using the Medication Adherence Response Scale (MARS), and compared to measured urinary prednisolone and metabolites in order to determine: 1. the prevalence of suboptimal adherence by each method; 2. the ability of MARS to predict urinary steroid detection.Methods: Participants completed the MARS, and/or provided urine samples (analysed for prednisolone and metabolites by LCMS). The performance characteristics of the MARS predicting undetected urinary steroid were calculated in the subgroup having both tests.Results: 181 participants currently taking regular oral corticosteroids were included, 59% female, mean (SD) age 54(12)yrs, FEV1 64.7(20.4)% predicted. Sub-optimal adherence (MARS score < 4.5) was reported in 62 participants, and 76 did not have detectable urinary prednisolone or metabolites. Good adherence by both methods was detected in only 52 participants (34%, see table). There was no difference in daily prednisolone dose between detectable and undetectable metabolites groups (p=0.848).Conclusion: Low levels of adherence to treatment in severe asthma is a common problem, when measured either directly or self-reported. There was very poor agreement (48% concordance) between these two methods, and we suggest that, for now both approaches should be used.
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  • Badi, Yusef Eamon, et al. (författare)
  • Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma
  • 2022
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 149:1, s. 89-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P <.05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P <.05) and particularly in neutrophilic and mixed granulocytic sputum (P <.05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
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  • Bakke, Ingunn, et al. (författare)
  • Mucosal and faecal neutrophil gelatinase-associated lipocalin as potential biomarkers for collagenous colitis
  • 2021
  • Ingår i: Journal of gastroenterology. - : Springer Nature. - 0944-1174 .- 1435-5922. ; 56:10, s. 914-927
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Collagenous colitis (CC) is an inflammatory bowel disease where chronic diarrhoea is the main symptom. Diagnostic markers distinguishing between CC and other causes of chronic diarrhoea remain elusive. This study explores neutrophil gelatinase-associated lipocalin (NGAL) and its mRNA lipocalin2 (LCN2) as histological and faecal disease markers in CC. Methods NGAL/LCN2 were studied in colonic biopsies from CC patients before and during budesonide treatment using RNA sequencing (n = 9/group), in situ hybridization (ISH) (n = 13-22/group) and immunohistochemistry (IHC) (n = 14-25/group). Faecal samples from CC (n = 3-28/group), irritable bowel syndrome diarrhoea (IBS-D) (n = 14) and healthy controls (HC) (n = 15) were assayed for NGAL and calprotectin. Results NGAL/LCN2 protein and mRNA expression were upregulated in active CC vs HC, and vs paired samples of treated CC in clinical remission. IHC and ISH localized increased NGAL/LCN2 mainly to epithelium of active CC, compared to almost absence in HC and treated CC. In contrast, calprotectin was solely expressed in immune cells. Despite great individual differences, faecal NGAL was significantly increased in active CC compared to HC, IBS-D and treated CC and had high test sensitivity. Faecal calprotectin levels were variably increased in active CC, but the values remained below usual clinical cut-offs. Conclusion NGAL/LCN2 is upregulated in the epithelium of active CC and reduced during budesonide-induced clinical remission to the level of HC and IBD-S. This was reflected in NGAL faecal concentrations. We propose NGAL as an IHC marker for disease activity in CC and a potential faecal biomarker discriminating CC from HC and IBS-D.
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  • Bakke, JV, et al. (författare)
  • Pet keeping and dampness in the dwelling : associations with airway infections, symptoms, and physiological signs from the ocular and nasal mucosa
  • 2007
  • Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 17:1, s. 60-69
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to utilize data from a study of occupational indoor environments to analyze symptoms and physiological signs in relation to the home environment. A medical investigation was performed at the workplace among university staff (n = 173) from four university buildings in Bergen, in March 2004. Tear film break up time (BUT) was measured by two methods. Nasal patency was measured by acoustic rhinometry. Nasal lavage fluid analysis (NAL) included eosinophilic cationic protein (ECP); myeloperoxidase (MPO), lysozyme and albumin. Atopy was assessed by total serum IgE and specific IgE (Phadiatop®). Totally 21%, 21%, 18%, 11%, and 27% had weekly ocular, nasal, facial dermal symptoms, headache and tiredness, respectively, 15% had a damp dwelling, and 20% had a cat or dog. Multiple linear or logistic regressions were applied, controlling for age gender, smoking, and environmental factors. Building dampness was associated with increased NAL-lysozyme (P = 0.02) and an increase of airway infections [odd ratio (OR) = 3.14, P = 0.04]. Pet keeping was associated with difficulties to concentrate (OR = 5.10, P = 0.001), heavy headedness (OR = 4.35, P = 0.004), four more days with tiredness per month (P = 0.04), and less airway infections (OR = 0.32; P = 0.02). In conclusion, pet keeping was associated with more central nervous system (CNS)-symptoms but less airway infections. Dampness in the dwelling may have inflammatory effects on the airway mucosa, possibly mediated via increased infection proneness.
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  • Bakke, Jan Vilhelm, et al. (författare)
  • Atopy, symptoms and indoor environmental perceptions, tear film stability, nasal patency and lavage biomarkers in university staff
  • 2008
  • Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 81:7, s. 861-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Study associations between airway symptoms, complaints on environmental perceptions, atopy definitions and biomarkers including tear film stability (BUT), nasal patency and nasal lavage (NAL). Personal predictors (gender, age, smoking, infections) for the biomarkers as well as associations between the biomarkers were also assessed. Methods A cross-sectional study of 173 employees in four university buildings, response rate 86%. Tear film break up time (BUT) was measured by a non-invasive method (NIBUT) and self-reported (SBUT). NAL-analysis included eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Total serum IgE, and specific IgE using Phadiatop(R) was measured. Data on subjective symptoms, environmental perceptions and background data were collected by use of a questionnaire. Multiple regression analyses were applied. Results Mean age was 43 years, 21% had weekly ocular, 21% nasal, and 17% laryngeal symptoms. Women had more complaints on environmental perceptions, shorter BUT and less nasal patency. Neither atopy (Phadiatop) nor Total IgE or allergy in the family, but asthma and hay fever was associated with mucosal symptoms or perceptions. Subjects with positive Phadiatop had higher levels of all NAL-biomarkers. Those with ocular symptoms had shorter BUT. Nasal symptoms were related to respiratory infections and laryngeal symptoms to NAL-lysozyme. Perceiving dry air was associated with lower BUT and reduced nasal volume difference before and after decongestion. Older subjects had greater nasal patency, and less atopy. All NAL-biomarkers were positively correlated. Higher lysozyme level was associated with less nasal patency and greater nasal decongestion. Conclusions BUT and NAL-lysozyme was associated with ocular, nasal, laryngeal symptoms and indoor environmental perceptions. Ever having had asthma and ever having had hay fever were predictors for symptoms and perceived air quality, respectively. Phadiatop, Total IgE, familiar allergy and ever eczema were not associated to symptoms or perceived environments. Age, gender and Phadiatop were main predictors for ocular and nasal biomarkers.
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  • Bakke, Jan Vilhelm, et al. (författare)
  • Eczema Increases Susceptibility to PM10 in Office Indoor Environments
  • 2012
  • Ingår i: Archives of Environmental & Occupational Health. - : Informa UK Limited. - 1933-8244 .- 2154-4700. ; 67:1, s. 15-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective was to compare impact of indoor office environment on employees with eczema with those without eczema. Exposure was measured at 56 sites and modelled for 173 work places. Tear film stability, lysozyme in nasal lavage, immunoglobulin E (IgE), and Phadiatop were assessed, and symptoms and perceptions collected by questionnaires. Multiple regression analyses were applied, adjusted for age, gender, strain, current smoking, and respiratory infections. Those with eczema perceived temperature too high but not associated with measured temperature. They had increased lysozyme in nasal lavage associated with increased air temperature difference between 6 and 10 AM, more general and mucosal symptoms, and "dry or flushed facial skin" associated with airborne particulate matter less than 10 microns in diameter (PM10). Impact of PM10 was most pronounced among those with eczema previous 30 days. Having eczema might be an important predictor for subjective and objective responses to indoor environment.
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  • Bakke, Jan Vilhelm, et al. (författare)
  • Gender and the physical and psychosocial work environments are related to indoor air symptoms
  • 2007
  • Ingår i: Journal of Occupational and Environmental Medicine. - 1076-2752 .- 1536-5948. ; 49:6, s. 641-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess gender differences in self-reported symptoms, psychosocial, subjective, and objective physical environments. Methods: Staff (N = 173) in four university buildings were investigated by questionnaires, blood samples, and objective assessment of indoor environment (temperature, air velocity, relative humidity, CO2, and dust [PM10]). Analyses were performed by linear and logistic regressions. Results: Women reported health symptoms more often than did men and complained more about physical but not psychosocial factors. Men's symptoms and complaints were more specifically associated to air velocity and humidity. For both genders, symptoms were related to both strain (P = 0.02) and perceived physical environments (P = 0.01). Lower relative humidity in the range of 15% to 35% was associated with perception of too low temperature and dry air. Conclusion: Gender, psychosocial, and physical environment factors were related to symptoms and perceived indoor climate.
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  • Bakke, J V, et al. (författare)
  • Symptoms, complaints, ocular and nasal physiological signs in university staff in relation to indoor environment : temperature and gender interactions
  • 2008
  • Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 18:2, s. 131-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Symptoms, signs, perceptions, and objective measures were studied in university buildings. Two problem buildings with a history of dampness and complaints were compared with two control buildings. Health investigations among university staff were performed at the workplace (n = 173) including tear film stability [non-invasive break-up time (NIBUT) and self-reported break-up time (SBUT)], nasal patency (acoustic rhinometry), nasal lavage fluid analysis [NAL: eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin] and atopy by total serum IgE and IgE antibodies (Phadiatop (R)). Exposure assessment included inspections, thermal and atmospheric climate at 56 points modelled for all work sites. Multiple regressions were applied, controlling for age and gender. Exposure differences between problem buildings and controls were small, and variations between rooms were greater. Workers in the problem buildings had more general and dermal symptoms, but not more objective signs than the others. Adjusted day NIBUT and SBUT increased at higher night air temperatures, with B (95% CI) 0.6 (0.04-1.2) and 1.3 (-0.02 to 2.5), respectively. Higher relative humidity at mean day air temperature < 22.1 degrees C was associated with adjusted NIBUT and SBUT, with B (95% CI) 0.16 (0.03-0.29) and 0.37 (-0.01 to 0.75), respectively. Air velocity below recommended winter values and reduced relative humidity in the range of 15-30% were associated with dry air and too low temperature.
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  • Bakke, Kristin A, et al. (författare)
  • Levetiracetam reduces the frequency of interictal epileptiform discharges during NREM sleep in children with ADHD
  • 2011
  • Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 15:6, s. 532-538
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Symptoms of attention deficit hyperactivity disorder (ADHD) are more common in children with epilepsy than in the general paediatric population. Epileptiform discharges in EEG may be seen in children with ADHD also in those without seizure disorders. Sleep enhances these discharges which may be suppressed by levetiracetam. AIM: To assess the effect of levetiracetam on focal epileptiform discharges during sleep in children with ADHD. METHOD: In this retrospective study a new semi-automatic quantitative method based on the calculation of spike index in 24-h ambulatory EEG recordings was applied. Thirty-five ADHD children, 17 with focal epilepsy, one with generalised epilepsy, and 17 with no seizure disorder were evaluated. Follow-up 24-h EEG recordings were performed after a median time of four months. RESULTS: Mean spike index was 50 prior to levetiracetam treatment and 21 during treatment. Seventeen children had no focal interictal epileptiform discharges in EEG at follow-up. Five children had a more than 50% reduction in spike index. Thus, a more than 50% reduction in spike index was found in 22/35 children (63%). Out of these an improved behaviour was noticed in 13 children (59%). CONCLUSION: This study shows that treatment with levetiracetam reduces interictal epileptiform discharges in children with ADHD. There is a complex relationship between epilepsy, ADHD and epileptiform activity, why it is a need for prospective studies in larger sample sizes, also to ascertain clinical benefits.
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  • Bakke, Merete, et al. (författare)
  • Development and evaluation of a comprehensive screening for orofacial dysfunction.
  • 2007
  • Ingår i: Swedish dental journal. - 0347-9994. ; 31:2, s. 75-84
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to develop a comprehensive screening instrument for evaluation of orofacial dysfunction that was easy to perform for different health professionals without special equipment. The Nordic Orofacial Test--Screening (NOT-S), consisting of a structured interview and clinical examination,was developed with a picture manual illustrating the different tasks in the examination. It was first tested in a Swedish version, and later translated to other Nordic languages, and to English. The interview reflected six domains, (I) Sensory function, (II) Breathing, (III) Habits, (IV) Chewing and swallowing, (V) Drooling, and (VI) Dryness of the mouth, and the examination included six domains representing (1) The face at rest, and tasks regarding (2) Nose breathing, (3) Facial expression, (4) Masticatory muscle and jaw function, (5) Oral motor function, and (6) Speech. One or more "yes" for impairment in a domain resulted in one point (maximum NOT-S score 12 points). The mean NOT-S score (+/- SD) in 120 patients (3-86 yr), referred to five centers for specialized dental care or speech and language pathology in Sweden, Norway and Denmark, was 4.1 +/- 2.6, and 0.4 +/- 0.6 in 60 control subjects (3-78 yr). The screening was easy to administer and the time spent 5-13 min. The scores from the clinic-referred sample differed significantly from the controls, and the sensitivity of the screening was 0.96 and specificity 0.63. Repeated evaluations of videotapes of 200 patients by 3 examiners, speech-language pathologists and dentists, with at least two-week intervals, showed inter- and intraexaminer agreement on the points given in the domains at respectively 83% and 92-95% which increased after recalibration to 85% and 95-99%. Kappa values for interexaminer agreement on the NOT-S scores were 0.42-0.44 (i.e. fair), and the method error was 5.3%. To conclude, NOT-S gave a reliable and valid screening for orofacial dysfunction.
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  • Bakke, Merete, et al. (författare)
  • Modified condylotomy versus conventional conservative treatment in painful reciprocal clicking-a preliminary prospective study in eight patients
  • 2008
  • Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 12:4, s. 353-359
  • Tidskriftsartikel (refereegranskat)abstract
    • Modified condylotomy may be relevant in severe painful reciprocal clicking of the temporomandibular joint (TMJ) where conservative treatment is insufficient. The effect of the modified condylotomy was analyzed and compared with conventional nonsurgical treatment in a randomized pilot study of eight patients, 19-44 years of age, with severe painful reciprocal clicking. Before and after treatment, assessments were performed by subjective reports, clinical recordings, and blinded evaluations of radiography and magnetic resonance imaging (MRI). Based on the clinical evaluations before treatment, all conditions were disc displacements with reduction and arthralgia (Research diagnostic criteria for temporomandibular disorders), but based on MRI, one patient had disc displacement without reduction and another had normal disc position. The treatment effect was significantly better and the disorders were significantly more reduced with condylotomy than with conventional nonsurgical treatment (P < 0.05, Mann-Whitney U test). In the surgical group, the clicking and locking had disappeared, the pain during function was significantly reduced (P < 0.05, Friedman ANOVA), and in two patients the disc position was normalized. The clicking still persisted in the nonsurgical patients and the disc position was unchanged. Our conclusion is that modified condylotomy is a promising option to reduce symptoms and signs in severe painful reciprocal clicking.
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  • Bakke, Marit (författare)
  • Regulation of steroidogenesis : cAMP-dependent transcription in adrenocortical cells
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Optimal steroid hormone output from the adrenal cortex depends on the peptide hormone ACTH which elicits its effect by increasing the intracellular levels of the second messenger cAMP, and a subsequent activation of the cAMP-dependent protein kinase. An important aspect of ACTH action is the ability of this hormone to increase transcription of a group of genes that encodes the steroid hydroxylases, enzymes that catalyze the conversion of cholesterol to biologically active steroids. A general feature of these genes is that they depend on atypical cAMP-responsive sequences not found in other genes that are regulated by this second messenger. A major focus of this thesis was to investigate the molecular mechanisms underlying cAMP-induced transcription of the gene encoding cytochrome P450 17alpha-hydroxylase (CYP17). This enzyme is necessary for syntbesis of cortisol and adrenal androgens. CYP17 contains two sequences in its promoter region that mediate cAMP-responsiveness on reporter genes when transfected into steroidogenic cells. These sequences, which are designated cAMP-responsive sequences 1 and 2 (CRS1 and CRS2), display differences with regard to nucleotide sequence and protein interactions. CRS1 and CRS2 are also differently regulated by the protein kinase C signal transduction pathway, since treatment of adrenocortical cells with phorbol esters represses cAMP-induced transcription mediated by CRS1, but has no effect on transcription conferred by CRS2. The mouse VL30 elements constitute a family of retrotransposons that are highly inducible by various physiological stimuli, and in steroidogenic tissues, VL30 expression is induced in response to tropic hormones. We identified DNA regulatory elements that mediated the ACTH-dependent transcription of a VL30 retrotransposon in mouse adrenal cells. These elements were related to classical cAMP regulatory elements (CREs) but exhibited differences in protein binding both with respect to affinity and specificity, suggesting that steroidogenic-cell specific gene expression in response to cAMP can be mediated both through DNA sequences related to classical CREs as well as through atypical cAMP-responsive sequences present in the steroid hydroxylase genes. Taken together, the results presented in this thesis provide new insights into the molecular aspects of ACTH action on steroid hormone biosynthesis, and also unravel novel aspects of cAMP-dependent gene regulation.
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  • Bakke-McKellep, A. M., et al. (författare)
  • Effects of dietary soybean meal and photoperiod cycle on osmoregulation following seawater exposure in Atlantic salmon smolts
  • 2006
  • Ingår i: Journal of Fish Biology. - : Wiley. - 0022-1112 .- 1095-8649. ; 69:5, s. 1396-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • Atlantic salmon Salmo salar juveniles were fed either fishmeal-based diets (FM) or diets in which soybean meal (SBM) partly replaced the FM from first feeding on. The fish were kept at continuous daylight during the juvenile stage. During the last 3 weeks before reaching 100 g body mass, all fish were subjected to 12L:12D. Starting at 100 g body mass, groups of 60 fish from each feeding background were subjected to continuous light for 12 weeks (short winter), or a square-wave photoperiod cycle to stimulate parr to smolt transformation with 8L:16D during the first 6 weeks, and then continuous light during the last 6 weeks (long winter). After the 12 weeks, 20 fish from each treatment were subjected to 0, 24 or 96 h seawater exposure at a water salinity of 34. Hypo-osmoregulatory ability at seawater exposure was assessed by mortality, intestinal pathology, plasma ion concentrations and osmolality, gill Na+/K+-ATPase activity and element concentrations in the cytoplasm of distal intestinal enterocytes using X-ray microanalysis. The hypo-osmoregulatory capacity was higher in fish kept at short winter than at long winter, apparently due to more rapid development of gill Na+/K+-ATPase activity. Fish fed SBM suffered typical soybean meal-induced histological alterations of the distal intestine and apparent reductions in digestive function in the more proximal gastrointestinal regions. The net osmoregulatory capacity of these fish was maintained, as indicated by higher gill Na+/K+-ATPase activity and lower plasma Na+, Ca2+ and osmolality compared to the FM-fed fish. Thus, feeding SBM did not impair the hypo-osmoregulatory ability of the Atlantic salmon following seawater exposure.
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  • Bakke, PS, et al. (författare)
  • Recommendations for epidemiological studies on COPD
  • 2011
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 38:6, s. 1261-1277
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease
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  • Bakke, Tove Margrethe, 1953- (författare)
  • Gjør MPA - utdanningen noen forskjell? : En studie av MPA -kandidatenes vurderinger av studiets effekter på ledelse, karriere og nettverk.
  • 2008
  • Annan publikation (populärvet., debatt m.m.)abstract
    • The choice of research theme is motivated by an interest of how theory influences practices. The MPA study programme is designed with a special emphasis on management practices, and the impact of these practices will develop over time.  A retrospective research design is therefore chosen for studying how former students assess the impact of the study. Throughout the programme, student experiences and opinions are monitored on a regular basis, whereas there are few studies of the long-term impacts of the study. Hence, The University College of Hedmark and the University of Karlstad have expressed their interest in this retrospective study. Commencing with the explicit formulation of the aims and goals of the study programme, I have designed a survey for analyzing how former students perceive the impact of the study. My aim is to investigate their assessment of the MPA study programme for their current work practices, and for their career development. The research question is: In retrospect, how do you assess the impact and importance of the MPA study programme for you as a manager and / or employee in the public sector? I have chosen to address three aspects: The impact for the conduct of their profession, and their role as managers The impact on their career development The impact for the establishment and maintenance of professional networks In this thesis, my aim is to investigate the former MPA-students’ assessment of the study programme.  While acknowledging the major role of other, external factors, it is the goal to identify the distinctive impact of the MPA programme.  Within the scope of this thesis, a structured survey approach is chosen, with the possibility of providing supplementary comments. The current study encompasses the students from the first two classes, receiving their education in the years 1999-2005 (MPAI and MPAII). Based on the formulated goals of the study programme, it addresses the former students’ assessment of the impact of the programme on management skills and practices, career development, and network establishment and maintenance. The study takes as its starting point the theories of management and leadership, as formulated in the works of Tor Busch and Joan Ole Vanebo, and quantitative methodology as formulated by Ottar Hellevik. Based on the responses to the survey, it seems clear that the former students give positive assessments of the programme for their subsequent management practices, career development, and networking, and that the programme thereby seems to have achieved its goals and ambitions.  One possible exception is that no one reports cross-national networking resulting from the programme. A dominant trend is that women give a more positive assessment of the impact of the programme for their management skills, and their career development. The study shows no significant differences between the two classes MPAI and MPAII, neither are there significant differences between the Swedish and the Norwegian respondents.
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  • Bakke, T., et al. (författare)
  • Polymeric optical spot-size transformer with vertical and lateral tapers
  • 2002
  • Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 20:7, s. 1188-1197
  • Tidskriftsartikel (refereegranskat)abstract
    • The design, fabrication, and characterization of a polymeric optical spot-size transformer with vertical and lateral tapers is reported. The vertical taper is formed by utilizing the planarization properties of a polymer, while the lateral taper is defined by photolithography. An optimization method for the taper shape is described based on fundamental results from coupled local mode theory. A total fiber to waveguide insertion loss of 0.6 dB has been measured with the integration of the transformer, an improvement of 2.1 dB. The spatial alignment tolerance for 1 dB excess loss was measured to ±2.7 µm, consistent with theory.
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  • Bergendal, Birgitta, et al. (författare)
  • Profiles of orofacial dysfunction in different diagnostic groups using the Nordic Orofacial Test (NOT-S)-A review
  • 2014
  • Ingår i: Acta Odontologica Scandinavica. - : Informa Healthcare. - 0001-6357 .- 1502-3850. ; 72:8, s. 578-584
  • Forskningsöversikt (refereegranskat)abstract
    • Objective. The Nordic Orofacial Test-Screening (NOT-S) was developed as a comprehensive method to assess orofacial function. Results from the screening protocol have been presented in 11 international publications to date. This study reviewed these publications in order to compile NOT-S screening data and create profiles of orofacial dysfunction that characterize various age groups and disorders. Materials and methods. NOT-S results of nine reports meeting the inclusion criteria were reviewed. Seven of these studies not only provided data on the mean and range of total NOT-S scores, but also on the most common domains of orofacial dysfunction (highest rate of individuals with dysfunction scores), allowing the construction of orofacial dysfunction profiles based on the prevalence of dysfunction in each domain of NOT-S. Results. The compiled data comprised 669 individuals, which included healthy control subjects (n = 333) and various patient groups (n = 336). All studies reported differences between individuals with diagnosed disorders and healthy control subjects. The NOT-S data could measure treatment effects and provided dysfunction profiles characterizing the patterns of orofacial dysfunction in various diagnoses. Conclusions. This review corroborates previous results that the NOT-S differentiates well between patients and healthy controls and can also show changes in individuals after treatment. NOT-S could be used as a standard instrument to assess orofacial dysfunction, evaluate the outcomes of oral habilitation and rehabilitation and improve comparability in clinical practice and research.
  •  
37.
  • Blauhut, Veit, et al. (författare)
  • Lessons from the 2018-2019 European droughts : a collective need for unifying drought risk management
  • 2022
  • Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981. ; 22:6, s. 2201-2217
  • Tidskriftsartikel (refereegranskat)abstract
    • Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets.
  •  
38.
  • Blauhut, Veit, et al. (författare)
  • Lessons from the 2018–2019 European droughts: A collective need for unifying drought risk management
  • 2021
  • Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazardous severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts, and how the hazard is perceived by relevant stakeholders for inducing action. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard and impacts. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders’ perceptions of drought, impacts on water resources and beyond, water availability and current drought management strategies at national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perceptions across different countries and in values of implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study concludes with an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and lessen harm to human and natural potentials.
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39.
  • Bleiker, Simon J., et al. (författare)
  • Cost-Efficient Wafer-Level Capping for MEMS and Imaging Sensors by Adhesive Wafer Bonding
  • 2016
  • Ingår i: Micromachines. - Basel, Switzerland : Multidisciplinary Digital Publishing Institute (MDPI). - 2072-666X. ; 7:10, s. 192-
  • Tidskriftsartikel (refereegranskat)abstract
    • Device encapsulation and packaging often constitutes a substantial part of the fabrication cost of micro electro-mechanical systems (MEMS) transducers and imaging sensor devices. In this paper, we propose a simple and cost-effective wafer-level capping method that utilizes a limited number of highly standardized process steps as well as low-cost materials. The proposed capping process is based on low-temperature adhesive wafer bonding, which ensures full complementary metal-oxide-semiconductor (CMOS) compatibility. All necessary fabrication steps for the wafer bonding, such as cavity formation and deposition of the adhesive, are performed on the capping substrate. The polymer adhesive is deposited by spray-coating on the capping wafer containing the cavities. Thus, no lithographic patterning of the polymer adhesive is needed, and material waste is minimized. Furthermore, this process does not require any additional fabrication steps on the device wafer, which lowers the process complexity and fabrication costs. We demonstrate the proposed capping method by packaging two different MEMS devices. The two MEMS devices include a vibration sensor and an acceleration switch, which employ two different electrical interconnection schemes. The experimental results show wafer-level capping with excellent bond quality due to the re-flow behavior of the polymer adhesive. No impediment to the functionality of the MEMS devices was observed, which indicates that the encapsulation does not introduce significant tensile nor compressive stresses. Thus, we present a highly versatile, robust, and cost-efficient capping method for components such as MEMS and imaging sensors.
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40.
  • Bohm, S., et al. (författare)
  • Cooperating nonconsensus cAMP-responsive elements are mediators of adrenocorticotropin-induced VL30 transcription in steroidogenic adrenal cells
  • 1993
  • Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 268:6, s. 3952-3963
  • Tidskriftsartikel (refereegranskat)abstract
    • Pituitary-derived trophic hormones regulate cell-type-specific expression of VL30 retrotransposons in tissues that are engaged in steroidogenesis. We show that adrenocorticotropic hormone and forskolin induced VL30 transcription in the steroidogenic adrenal cell line Y1 and that the transcriptional activation was cell type- and protein kinase A-dependent. Three novel cAMP-responsive elements (CREs), within the VL30 long terminal repeat, were identified and shown to activate transcription synergistically when templates bearing multiple sites were compared with templates bearing a single site. This type of regulation was evident only in forskolin-treated cells, and the response elements were found to be inactive as mediators of constitutive transcription. In vitro binding analyses indicated that a consensus CRE and the nonconsensus VL30 CREs differ with respect to binding affinity and specificity to a number of nuclear factors that were identified to be related to proteins within the CREB, Jun, and C/EBP families of transcription factors. The relatively low affinity and/or a restricted binding specificity of the VL30 CREs made it possible to detect forskolin-induced binding of CREB- and Jun-related proteins to these sequences. We suggest that cAMP-induced transcription, specific for steroidogenic cells, can be mediated by a novel type of nonconsensus CREs and that the mechanism for this type of gene regulation is distinct from that mediated through a consensus CRE. We also report the identification of a novel factor, distinct from previously characterized CRE-binding proteins, that constitutively binds to the identified CREs.
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41.
  • Brandsma, Joost, et al. (författare)
  • Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers
  • 2018
  • Ingår i: Metabolomics. - : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 14:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.
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42.
  • Brandsma, Joost, et al. (författare)
  • Stratification of asthma by lipidomic profiling of induced sputum supernatant
  • 2023
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 152:1, s. 117-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.Methods: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes.Results: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.Conclusion: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.
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43.
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44.
  • Brinkman, Paul, et al. (författare)
  • Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:5, s. 1811-1820.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.
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45.
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46.
  • Bruserud, Oyvind, et al. (författare)
  • A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1
  • 2016
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:8, s. 2975-2983
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceasedsiblingswithahighprobability of undisclosed APS1. All except three had interferon-omega) autoantibodies, and allhadorgan-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-omega) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.
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47.
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48.
  • Bukmann Larsen, Pia, et al. (författare)
  • The microINR portable coagulometer: analytical quality and user-friendliness of a PT (INR) point-of-care instrument
  • 2017
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 77:2, s. 115-121
  • Tidskriftsartikel (refereegranskat)abstract
    • Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR((R))) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olavs University Hospital, Trondheim, Norway (n=98) and from two PHCCs (n=88). Venous blood samples were analyzed under optimal conditions on the STA-R((R))Evolution with STA-SPA+reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR((R)). The imprecision of the microINR((R)) was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR 2.5. The microINR((R)) did not meet the SKUP quality requirement for imprecision 5.0%. For INR amp;lt;2.5 at PHCC2 and at both levels in PHCC1, CV% was 5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.
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49.
  • Burg, Dominic, et al. (författare)
  • Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
  • 2018
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:6, s. 2072-2091
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
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50.
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