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  • 151. Assi, Nada
    et al.
    Gunter, Marc J.
    Thomas, Duncan C.
    Leitzmann, Michael
    Stepien, Magdalena
    Chajès, Véronique
    Philip, Thierry
    Vineis, Paolo
    Bamia, Christina
    Boutron-Ruault, Marie-Christine
    Sandanger, Torkjel M.
    Molinuevo, Amaia
    Boshuizen, Hendriek
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kühn, Tilman
    Travis, Ruth
    Overvad, Kim
    Riboli, Elio
    Scalbert, Augustin
    Jenab, Mazda
    Viallon, Vivian
    Ferrari, Pietro
    Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort2018Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 108, nr 1, s. 117-126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.

    Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.

    Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.

    Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

  • 152. Assi, Nada
    et al.
    Thomas, Duncan C.
    Leitzmann, Michael
    Stepien, Magdalena
    Chajès, Véronique
    Philip, Thierry
    Vineis, Paolo
    Bamia, Christina
    Boutron-Ruault, Marie-Christine
    Sandanger, Torkjel M.
    Molinuevo, Amaia
    Boshuizen, Hendriek C.
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Kühn, Tilman
    Travis, Ruth C.
    Overvad, Kim
    Riboli, Elio
    Gunter, Marc J.
    Scalbert, Augustin
    Jenab, Mazda
    Ferrari, Pietro
    Viallon, Vivian
    Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC2018Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 27, nr 5, s. 531-540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.

    Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.

    Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.

    Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.

    Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators.

  • 153. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017Inngår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, s. 209-216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

  • 154. Atkins, Isabelle
    et al.
    Kinnersley, Ben
    Ostrom, Quinn T.
    Labreche, Karim
    Il'yasova, Dora
    Armstrong, Georgina N.
    Eckel-Passow, Jeanette E.
    Schoemaker, Minouk J.
    Nothen, Markus M.
    Barnholtz-Sloan, Jill S.
    Swerdlow, Anthony J.
    Simon, Matthias
    Rajaraman, Preetha
    Chanock, Stephen J.
    Shildkraut, Joellen
    Bernstein, Jonine L.
    Hoffman, Per
    Jockel, Karl-Heinz
    Lai, Rose K.
    Claus, Elizabeth B.
    Olson, Sara H.
    Johansen, Christoffer
    Wrensch, Margaret R.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Jenkins, Robert B.
    Sanson, Marc
    Bondy, Melissa L.
    Houlston, Richard S.
    Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma2019Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, nr 8, s. 2065-2071Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 x 10(-6), candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 x 10(-6)). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.

    Significance: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

  • 155.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Hultling, Claes
    Department of Neurobiology, Care Sciences and Society (Neurorehabilitation), Karolinska Institute, Stockholm, Sweden.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury2015Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 5, s. 426-431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel ethodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury. Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback. Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury. Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

  • 156.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Imlook4d: introducing an extendable research 4d analysis software2014Inngår i: XII Turku PET Symposium, 24-27 May 2014, Turku, Finland: the symposium of Nordic Association for Clinical Physics (NACP), 2014, s. 63-63Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Imlook4d (http://www.dicom-port.com) is a free Matlab based graphical user interface (GUI) tool useful for static, dynamic and gated PET studies.  It supports reading and writing DICOM, Nifti, Analyze, ECAT.  The DICOM reader is orders of magnitude faster than the Matlab imaging toolbox.  Imlook4d requires no additional Matlab toolboxes.

    The main benefit with imlook4d is that it is easily extendable with scripts, accessing exported variables such as the image matrix (4D) and a region-of-interest (ROI) matrix.  Scripts are available via a menu in the imlook4d GUI, and can be used to manipulate the image-matrix and ROI data.  There is also a menu option to export and import these variables to the Matlab workspace for interactive manipulation, useful for one-off fixes or for script development.  There are presently about 30 scripts in categories such as ROI, Matrix, Header info etc.  There is also direct export to ImageJ [1] and import back from ImageJ, thus giving access to all tools available within ImageJ.

    Imlook4d has a built in volume-of-interest editor, with a brush tool for quick interactive ROI delineation, and via scripts, different ways of thresholding ROIs from parts of the image.  Time activity data is saved to a tab-delimited text file.

    The principal-component (PC) based Hotelling filter is an integrated part of the program, which allows for interactive noise reduction without loss of quantitation [2].  A typical work flow for a dynamic data set is to turn on the filter for ROI delineation, and then there is the choice of turning it off for export of time-activity data.  Also the PC images can be used to draw ROIs on, which under some circumstances gives enhanced contrast.

    Calculation of parametric pharmacokinetic modelling images can be performed interactively, calculated slice by slice as the user scrolls through the volume.  Reference models for Patlak, Logan and Averaged Simple Flow Model [3]  applied on 15O-water are implemented, and it is relatively easy to implement other kinetic models.  Similarly, scripts have been developed for regional Patlak and Logan models on ROI data.

    [1] Rasband, WS, ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, http://imagej.nih.gov/ij/, 1997-2014

    [2] Axelsson J, Sörensen J, The 2D Hotelling filter - a quantitative noise-reducing principal-component filter for dynamic PET data, with applications in patient dose reduction. BMC Med Phys. 2013 Apr 10;13:1. doi: 10.1186/1756-6649-13-1.

    [3] Yoshida, K, Mullani, N and Gould KL, Coronary Flow and Flow Reserve by PET Simplified for Clinical Applications Using Rubidium-82 or Nitrogen-13-Ammonia, J Nucl Med 1996; 37:1701-1712

    Figure 1.  The imlook4d GUI with the user SCRIPTS menu selected.  The group of ROI scripts was further selected.  In the underlying image, a rough ROI is created.  

  • 157.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    PET/MR ur fysikerns perspektiv2015Konferansepaper (Annet vitenskapelig)
  • 158.
    Axelsson, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sörensen, Jens
    PET-center, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
    The 2D Hotelling filter: a quantitativenoise-reducing principal-component filter fordynamic PET data, with applications in patientdose reduction2013Inngår i: BMC Medical Physics, ISSN 1756-6649, Vol. 13, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In this paper we apply the principal-component analysis filter (Hotelling filter) to reduce noise fromdynamic positron-emission tomography (PET) patient data, for a number of different radio-tracer molecules. Wefurthermore show how preprocessing images with this filter improves parametric images created from suchdynamic sequence.We use zero-mean unit variance normalization, prior to performing a Hotelling filter on the slices of a dynamictime-series. The Scree-plot technique was used to determine which principal components to be rejected in thefilter process. This filter was applied to [11C]-acetate on heart and head-neck tumors, [18F]-FDG on liver tumors andbrain, and [11C]-Raclopride on brain. Simulations of blood and tissue regions with noise properties matched to realPET data, was used to analyze how quantitation and resolution is affected by the Hotelling filter. Summing varyingparts of a 90-frame [18F]-FDG brain scan, we created 9-frame dynamic scans with image statistics comparable to 20MBq, 60 MBq and 200 MBq injected activity. Hotelling filter performed on slices (2D) and on volumes (3D) werecompared.Results: The 2D Hotelling filter reduces noise in the tissue uptake drastically, so that it becomes simple to manuallypick out regions-of-interest from noisy data. 2D Hotelling filter introduces less bias than 3D Hotelling filter in focalRaclopride uptake. Simulations show that the Hotelling filter is sensitive to typical blood peak in PET prior to tissueuptake have commenced, introducing a negative bias in early tissue uptake. Quantitation on real dynamic data isreliable. Two examples clearly show that pre-filtering the dynamic sequence with the Hotelling filter prior toPatlak-slope calculations gives clearly improved parametric image quality. We also show that a dramatic dosereduction can be achieved for Patlak slope images without changing image quality or quantitation.Conclusions: The 2D Hotelling-filtering of dynamic PET data is a computer-efficient method that gives visuallyimproved differentiation of different tissues, which we have observed improve manual or automated regionof-interest delineation of dynamic data. Parametric Patlak images on Hotelling-filtered data display improved clarity,compared to non-filtered Patlak slope images without measurable loss of quantitation, and allow a dramaticdecrease in patient injected dose.

  • 159. Baba, Kerstin
    et al.
    Fransson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lindh, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Use of a modified ESAS in cancer patients: a pilot study of patient and staff experiences2007Inngår i: International Journal of Palliative Nursing, ISSN 1357-6321, E-ISSN 2052-286X, Vol. 13, nr 12, s. 610-616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To evaluate the feasibility of a modified Edmonton Symptom Assessment Scale (ESAS) for monitoring symptoms in oncological palliative care.

    Methods: A modified ESAS was delivered daily to 28 patients with advanced cancer. A questionnaire to discover staff members’ opinions on the ESAS was delivered at the end of the study. Structured interviews were used to examine patients’ opinions on the ESAS.

    Results: The mean total ESAS score was 28.9 on inclusion day and 25.8 on Day 3 (p=0.531). Eleven of 21 of the staff considered the ESAS to be a ‘good’ or ‘very good’ way to obtain information about patients’ symptoms. Seventeen of 24 patients who participated in the interview felt that ESAS was easy to fill in, and that there were no missing questions.

    Conclusion: The patients felt that the modified ESAS contained relevant symptoms, and that the questionnaires were easy to fill in. The staff considered the modified ESAS to be a useful instrument for obtaining information about patients’ symptom distress. The modified ESAS is a good instrument for use as part of the daily clinical routine, as well as for monitoring symptoms in palliative oncological care.

  • 160.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine and training-related working-memory improvement2013Inngår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 9, s. 2209-2219Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.

  • 161. Baglietto, Laura
    et al.
    Ponzi, Erica
    Haycock, Philip
    Hodge, Allison
    Bianca Assumma, Manuela
    Jung, Chol-Hee
    Chung, Jessica
    Fasanelli, Francesca
    Guida, Florence
    Campanella, Gianluca
    Chadeau-Hyam, Marc
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ala, Ugo
    Provero, Paolo
    Wong, Ee Ming
    Joo, Jihoon
    English, Dallas R
    Kazmi, Nabila
    Lund, Eiliv
    Faltus, Christian
    Kaaks, Rudolf
    Risch, Angela
    Barrdahl, Myrto
    Sandanger, Torkjel M
    Southey, Melissa C
    Giles, Graham G
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Vineis, Paolo
    Polidoro, Silvia
    Relton, Caroline L
    Severi, Gianluca
    DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk2017Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 1, s. 50-61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled  = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled  = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled  = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled  = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled  = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity  ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.

  • 162.
    Bahar Gogani, Jalil
    et al.
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Hägglund, Peter
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Wickman, Göran
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Assessment of correlated dose and sensitivity profiles on a multi-slice CT scanner2005Inngår i: Radiat Prot Dosimetry, ISSN 0144-8420, Vol. 114, nr 1-3, s. 332-336Artikkel i tidsskrift (Fagfellevurdert)
  • 163. Bailey, D. L.
    et al.
    Pichler, B. J.
    Gueckel, B.
    Antoch, G.
    Barthel, H.
    Bhujwalla, Z. M.
    Biskup, S.
    Biswal, S.
    Bitzer, M.
    Boellaard, R.
    Braren, R. F.
    Brendle, C.
    Brindle, K.
    Chiti, A.
    la Fougere, C.
    Gillies, R.
    Goh, V.
    Goyen, M.
    Hacker, M.
    Heukamp, L.
    Knudsen, G. M.
    Krackhardt, A. M.
    Law, I.
    Morris, J. C.
    Nikolaou, K.
    Nuyts, J.
    Ordonez, A. A.
    Pantel, K.
    Quick, H. H.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sabri, O.
    Sattler, B.
    Troost, E. G. C.
    Zaiss, M.
    Zender, L.
    Beyer, Thomas
    Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tubingen, Germany2018Inngår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 20, nr 1, s. 4-20Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

  • 164. Bailey, D. L.
    et al.
    Pichler, B. J.
    Gueckel, B.
    Barthel, H.
    Beer, A. J.
    Botnar, R.
    Gillies, R.
    Goh, V.
    Gotthardt, M.
    Hicks, R. J.
    Lanzenberger, R.
    la Fougere, C.
    Lentschig, M.
    Nekolla, S. G.
    Niederdraenk, T.
    Nikolaou, K.
    Nuyts, J.
    Olego, D.
    Åhlstrom Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Signore, A.
    Schaefers, M.
    Sossi, V.
    Suminski, M.
    Veit-Haibach, P.
    Umutlu, L.
    Wissmeyer, M.
    Beyer, T.
    Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tubingen, Germany2016Inngår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 18, nr 5, s. 637-650Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tubingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

  • 165. Bailey-Wilson, Joan E
    et al.
    Childs, Erica J
    Cropp, Cheryl D
    Schaid, Daniel J
    Xu, Jianfeng
    Camp, Nicola J
    Cannon-Albright, Lisa A
    Farnham, James M
    George, Asha
    Powell, Isaac
    Carpten, John D
    Giles, Graham G
    Hopper, John L
    Severi, Gianluca
    English, Dallas R
    Foulkes, William D
    Maehle, Lovise
    Moller, Pal
    Eeles, Rosalind
    Easton, Douglas
    Guy, Michelle
    Edwards, Steve
    Badzioch, Michael D
    Whittemore, Alice S
    Oakley-Girvan, Ingrid
    Hsieh, Chih-Lin
    Dimitrov, Latchezar
    Stanford, Janet L
    Karyadi, Danielle M
    Deutsch, Kerry
    McIntosh, Laura
    Ostrander, Elaine A
    Wiley, Kathleen E
    Isaacs, Sarah D
    Walsh, Patrick C
    Thibodeau, Stephen N
    McDonnell, Shannon K
    Hebbring, Scott
    Lange, Ethan M
    Cooney, Kathleen A
    Tammela, Teuvo LJ
    Schleutker, Johanna
    Maier, Christiane
    Bochum, Sylvia
    Hoegel, Josef
    Gronberg, Henrik
    Wiklund, Fredrik
    Emanuelsson, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Cancel-Tassin, Geraldine
    Valeri, Antoine
    Cussenot, Olivier
    Isaacs, William B
    Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families2012Inngår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, s. 46-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.

    Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.

    Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.

    Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

  • 166. Bainbridge, Matthew N
    et al.
    Armstrong, Georgina N
    Gramatges, M Monica
    Bertuch, Alison A
    Jhangiani, Shalini N
    Doddapaneni, Harsha
    Lewis, Lora
    Tombrello, Joseph
    Tsavachidis, Spyros
    Liu, Yanhong
    Jalali, Ali
    Plon, Sharon E
    Lau, Ching C
    Parsons, Donald W
    Claus, Elizabeth B
    Barnholtz-Sloan, Jill
    Il'yasova, Dora
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S
    Jenkins, Robert B
    Lachance, Daniel
    Olson, Sara H
    Bernstein, Jonine L.
    Merrell, Ryan T
    Wrensch, Margaret R
    Walsh, Kyle M
    Davis, Faith G
    Lai, Rose
    Shete, Sanjay
    Aldape, Kenneth
    Amos, Christopher I
    Thompson, Patricia A
    Muzny, Donna M
    Gibbs, Richard A
    Melin, Beatrice S
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bondy, Melissa L
    Germline mutations in shelterin complex genes are associated with familial glioma2015Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, nr 1, artikkel-id dju384Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

  • 167. Baltar, Valéria Troncoso
    et al.
    Xun, Wei W
    Chuang, Shu-Chun
    Relton, Caroline
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Øivind
    Johansson, Mattias
    Slimani, Nadia
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, H Bas
    Boshuizen, Hendriek C
    van Gils, Carla H
    Peeters, Petra H M
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Castaño, José Maria Huerta
    Larrañaga, Nerea
    Pérez, Maria José Sánchez
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Tagliabue, Giovanna
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlota
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Rasmuson, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Roswall, Nina
    Tjønneland, Anne
    Riboli, Elio
    Brennan, Paul
    Vineis, Paolo
    Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort2011Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 5, s. 869-875Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index.

    Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001).

    Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels.

    Impact: This study strengthens the evidence for the benefits of a smoking ban in public places.

  • 168. Baltar, Valéria Troncoso
    et al.
    Xun, Wei W
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Ferrari, Pietro
    Chuang, Shu-Chun
    Relton, Caroline
    Ueland, Per Magne
    Midttun, Oivind
    Slimani, Nadia
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, Bas
    Boshuizen, Hendriek
    van Gils, Carla H
    Onland-Moret, N Charlotte
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Castaño, José Maria Huerta
    Larrañaga, Nerea
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Krogh, Vittorio
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Rasmuson, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Roswall, Nina
    Tjønneland, Anne
    Riboli, Elio
    Brennan, Paul
    Vineis, Paolo
    A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk2013Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, nr 8, s. 677-688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

  • 169. Bamia, Christina
    et al.
    Lagiou, Pagona
    Buckland, Genevieve
    Grioni, Sara
    Agnoli, Claudia
    Taylor, Aliki J.
    Dahm, Christina C.
    Overvad, Kim
    Olsen, Anja
    Tjonneland, Anne
    Cottet, Vanessa
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Grote, Verena
    Teucher, Birgit
    Boeing, Heiner
    Buijsse, Brian
    Trichopoulos, Dimitrios
    Adarakis, George
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Palli, Domenico
    Bueno-de-Mesquita, H. Bas
    van Duijnhoven, Fraenzel J. B.
    Peeters, Petra H. M.
    Engeset, Dagrun
    Skeie, Guri
    Lund, Eiliv
    Sanchez, Maria-Jose
    Barricarte, Aurelio
    Huerta, Jose-Maria
    Ramon Quiros, J.
    Dorronsoro, Miren
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Drake, Isabel
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nick
    Romieu, Isabelle
    Fedirko, Veronika
    Jenab, Mazda
    Romaguera, Dora
    Norat, Teresa
    Trichopoulou, Antonia
    Mediterranean diet and colorectal cancer risk: results from a European cohort2013Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, nr 4, s. 317-328Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.

  • 170. Barekati, Zeinab
    et al.
    Radpour, Ramin
    Kohler, Corina
    Zhang, Bei
    Toniolo, Paolo
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lv, Qing
    Zheng, Hong
    Zhong, Xiao Yan
    Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations2010Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, nr 15, s. 2936-2946Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14(ARF), MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14(ARF) and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P < 0.05 and <0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P < 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P < 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P < 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P < 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cancer.

  • 171. Barekati, Zeinab
    et al.
    Radpour, Ramin
    Lu, Qing
    Bitzer, Johannes
    Zheng, Hong
    Toniolo, Paolo
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Zhong, Xiao Yan
    Methylation signature of lymph node metastases in breast cancer patients2012Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, s. 244-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods: The quantitative methylation analysis was performed using the SEQUENOM's EpiTYPER (TM) assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results: The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. Conclusions: The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.

  • 172. Bartek, Jiri, Jr.
    et al.
    Förander, Petter
    Thurin, Erik
    Wangerid, Theresa
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Regional Cancer Centre Stockholm/Gotland, Stockholm, Sweden.
    Hesselager, Göran
    Jakola, Asgeir Store
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, artikkel-id 43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 173. Barton, Maria
    et al.
    Santucci-Pereira, Julia
    de Cicco, Ricardo Lopez
    Russo, Irma H.
    Ross, Eric A.
    Slifker, Michael
    Peri, Suraj
    Bordas, Pal
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Toniolo, Paolo
    Russo, Jose
    Long noncoding RNAs in the postmenopausal breast and their role in cancer prevention2014Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, nr 19Artikkel i tidsskrift (Annet vitenskapelig)
  • 174. Baste, Valborg
    et al.
    Hansson Mild, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Moen, Bente E
    Radiofrequency exposure on fast patrol boats in the Royal Norwegian Navy-an approach to a dose assessment.2010Inngår i: Bioelectromagnetics, ISSN 0197-8462, E-ISSN 1521-186X, Vol. 31, nr 5, s. 350-360Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemiological studies related to radiofrequency (RF) electromagnetic fields (EMF) have mainly used crude proxies for exposure, such as job titles, distance to, or use of different equipment emitting RF EMF. The Royal Norwegian Navy (RNoN) has measured RF field emitted from high-frequency antennas and radars on several spots where the crew would most likely be located aboard fast patrol boats (FPB). These boats are small, with short distance between the crew and the equipment emitting RF field. We have described the measured RF exposure aboard FPB and suggested different methods for calculations of total exposure and annual dose. Linear and spatial average in addition to percentage of ICNIRP and squared deviation of ICNIRP has been used. The methods will form the basis of a job exposure matrix where relative differences in exposure between groups of crew members can be used in further epidemiological studies of reproductive health. Bioelectromagnetics, 2010. (c) 2010 Wiley-Liss, Inc.

  • 175. Baste, Valborg
    et al.
    Moen, Bente E
    Oftedal, Gunnhild
    Strand, Leif Age
    Bjørge, Line
    Hansson Mild, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Pregnancy outcomes after paternal radiofrequency field exposure aboard fast patrol boats2012Inngår i: Journal of Occupational and Environmental Medicine, ISSN 1076-2752, E-ISSN 1536-5948, Vol. 54, nr 4, s. 431-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To investigate adverse reproductive outcomes among male employees in the Royal Norwegian Navy exposed to radiofrequency electromagnetic fields aboard fast patrol boats.

    Methods: Cohort study of Royal Norwegian Navy servicemen linked to the Medical Birth Registry of Norway, including singleton offspring born between 1967 and 2008 (n = 37,920). Exposure during the last 3 months before conception (acute) and exposure more than 3 months before conception (nonacute) were analyzed.

    Results: Perinatal mortality and preeclampsia increased after service aboard fast patrol boats during an acute period and also after increased estimated radiofrequency exposure during an acute period, compared with service aboard other vessels. No associations were found between nonacute exposure and any of the reproductive outcomes.

    Conclusions: Paternal work aboard fast patrol boats during an acute period was associated with perinatal mortality and preeclampsia, but the cause is not clear.

  • 176. Baste, Valborg
    et al.
    Oftedal, Gunnhild
    Møllerløkken, Ole Jacob
    Hansson Mild, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Moen, Bente E.
    Prospective study of pregnancy outcomes after parental cell phone exposure: the Norwegian mother and child cohort study2015Inngår i: Epidemiology, ISSN 1044-3983, Vol. 26, nr 4, s. 613-621Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Research about prenatal exposure to electromagnetic fields from cell phones among expectant parents and reproductive outcome is limited. The aim of this article is to investigate the association between pregnancy outcome and parental cell phone exposure in a large prospective study. Methods: The study was based on the Norwegian Mother and Child Cohort Study conducted during the decade 1999–2009. In that study, pregnant women were recruited before a routine ultrasound examination during gestational week 15; they answered a questionnaire at that time and again around gestational week 30. The expectant father was invited to answer a questionnaire during gestational week 15 (2001–2009). The forms contained questions regarding cell phone use. The response rate was 38.7% and the cohort comprised 100,730 singleton births. Pregnancy outcomes were obtained by linkage to the Medical Birth Registry of Norway. Results: The risk of preeclampsia was slightly lower among women with medium and high cell phone exposure compared with low exposure after adjusting for potential confounders. Fathers with testis exposure when using cell phones had a borderline increased risk of perinatal mortality among offspring and a slightly decreased risk of partner developing preeclampsia during pregnancy compared with no cell phone exposure of head or testis. None of the other pregnancy outcomes was associated with cell phone exposure. Conclusions: We found no association between maternal prenatal or paternal preconceptional cell phone exposure and any of the studied pregnancy outcomes. The only risk estimate suggesting a potential increased risk was not consistent with other findings.

  • 177. Bauer, H C
    et al.
    Alvegård, T A
    Berlin, O
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper.
    Kalén, A
    Lindholm, P
    Gustafson, P
    Smeland, S
    Trovik, C S
    The Scandinavian Sarcoma Group Register 1986-2001.2004Inngår i: Acta Orthopaedica Scandinavica (Supplementum), ISSN 0300-8827, Vol. 75, nr 311, s. 8-10Artikkel i tidsskrift (Fagfellevurdert)
  • 178.
    Bayisa, Fekadu
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Kuljus, Kristi
    Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia.
    Johansson, Adam
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bolin, David
    Department of Mathematical Sciences, Chalmers and University of Gothenburg, Gothenburg, Sweden.
    Yu, Jun
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Prediction of CT images from MR images with hidden Markov and random field models2016Inngår i: Proceedings of the 8th International Workshop on Spatio-Temporal Modelling / [ed] A. Iftimi, J. Mateu and F. Montes, 2016, s. 163-163Konferansepaper (Annet vitenskapelig)
  • 179.
    Bayisa, Fekadu L.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Liu, Xijia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Yu, Jun
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Computed Tomography Image Estimation by Statistical Learning MethodsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    There is increasing interest in computed tomography (CT) image estimations from magnetic resonance (MR) images. The estimated CT images canbe utilised for attenuation correction, patient positioning, and dose planningin diagnostic and radiotherapy workflows. This study presents a statisticallearning method for CT image estimation. We have used predefined tissuetype information in a Gaussian mixture model to explore the estimation.The performance of our method was evaluated using cross-validation on realdata. In comparison with the existing model-based CT image estimationmethods, the proposed method has improved the estimation, particularly inbone tissues. Evaluation of our method shows that it is a promising methodto generate CT image substitutes for the implementation of fully MR-basedradiotherapy and PET/MRI applications.

  • 180.
    Bayisa, Fekadu
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Liu, Xijia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Yu, Jun
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Statistical learning in computed tomography image estimation2018Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, nr 12, s. 5450-5460Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: There is increasing interest in computed tomography (CT) image estimations from magneticresonance (MR) images. The estimated CT images can be utilized for attenuation correction, patientpositioning, and dose planning in diagnostic and radiotherapy workflows. This study aims to introducea novel statistical learning approach for improving CT estimation from MR images and to compare theperformance of our method with the existing model-based CT image estimation methods.

    Methods: The statistical learning approach proposed here consists of two stages. At the trainingstage, prior knowledge about tissue types from CT images was used together with a Gaussian mixturemodel (GMM) to explore CT image estimations from MR images. Since the prior knowledge is notavailable at the prediction stage, a classifier based on RUSBoost algorithm was trained to estimatethe tissue types from MR images. For a new patient, the trained classifier and GMMs were used topredict CT image from MR images. The classifier and GMMs were validated by using voxel-leveltenfold cross-validation and patient-level leave-one-out cross-validation, respectively.

    Results: The proposed approach has outperformance in CT estimation quality in comparison withthe existing model-based methods, especially on bone tissues. Our method improved CT image estimationby 5% and 23% on the whole brain and bone tissues, respectively.

    Conclusions: Evaluation of our method shows that it is a promising method to generate CTimage substitutes for the implementation of fully MR-based radiotherapy and PET/MRI applications

  • 181.
    Beckman Rehnman, Jeannette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    New methods to evaluate the effect of conventional and modified crosslinking treatment for keratoconus2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Today corneal crosslinking with ultraviolet-A photoactivation of riboflavin is an established method to halt the progression of keratoconus. In some cases, when the refractive errors are large and the visual acuity is low, conventional corneal crosslinking may not be sufficient. In these cases it would be desirable with a treatment that both halts the progression and also reduces the refractive errors and improves the quality of vision.

    Aims:  The aims of this thesis were to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens could improve the optical and visual outcomes of the treatment, and also to find methods to evaluate the effect of different corneal crosslinking treatment regimens.

    Methods: In a prospective, open, randomized case-control study, 60 eyes of 43 patients with progressive keratoconus, aged 18-28 years, planned for routine corneal crosslinking, and a corresponding age- and sex-matched control group was included. The patients were randomized to conventional corneal crosslinking (CXL; n=30) or corneal crosslinking with mechanical compression of the cornea during the treatment (CRXL; n=30).

    Biomicroscopy, autorefractometry, best spectacle corrected visual acuity, axial length measurement, Pentacam® HR Scheimpflug photography, pachymetry, intraocular pressure measurements and corneal biomechanical assessments were performed before treatment (baseline) and at 1 month and 6 months after the treatment.

    One of the articles evaluated and compared the optical and visual outcomes between CXL and CRXL, while the other three articles focused on methods to evaluate treatment effects. In Paper I, the corneal light scattering was manually quantified from Scheimpflug images throughout the corneal thickness at 8 measurements points, 0.0 to 3.0 mm from the corneal centre, in patients treated with CXL. In Paper IV the corneal densitometry (light scattering) was measured with the Pentacam® HR software, in 4 circular zones around the corneal apex and at 3 different depths of the corneal stroma, in both CXL and CRXL treated corneas. Paper III quantified the biomechanical effects of CXL in vivo.

    Results: Corneal light scattering after CXL showed distinctive spatial and temporal profiles and Applanation Resonance Tonometry (ART) -technology demonstrated an increased corneal hysteresis 1 and 6 months after CXL. When comparing the refractive and structural results after CXL and CRXL, CRXL failed to flatten the cornea, and the treatment did not show any benefits to conventional CXL treatment, some variables even indicated an inferior effect. Accordingly, the increase in corneal densitometry was also less pronounced after CRXL.

    Conclusions: Analysis of corneal light scattering/densitometry shows tissue changes at the expected treatment location, and may be a relevant variable in evaluating the crosslinking effect. ART -technology is an in vivo method with the potential to assess the increased corneal hysteresis after CXL treatment. By refining the method, ARTmay become a useful tool in the future. Unfortunately, CRXL does not improve the optical and visual outcomes after corneal crosslinking. Possibly, stronger crosslinking would be necessary to stabilize the cornea in a flattened position.

  • 182.
    Beckman Rehnman, Jeannette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Behndig, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Increased corneal hysteresis after corneal collagen crosslinking: a study based on applanation resonance technology2014Inngår i: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 132, nr 12, s. 1426-1432Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Importance: A reliable tool for quantification of the biomechanical status of the cornea in conjunction with corneal collagen crosslinking (CXL) treatment is needed.

    Objective: To quantify the biomechanical effects of CXL in vivo.

    Design, Setting, and Participants: A prospective, open, case-control study was conducted at the Department of Ophthalmology, Umeå University, Umeå, Sweden. Participants included 28 patients (29 eyes) aged 18 to 28 years with progressive keratoconus and corresponding age- and sex-matched healthy individuals serving as controls. All participants were monitored during a 6-month period between October 13, 2009, and November 5, 2012.

    Main Outcomes and Measures: Corneal hysteresis after CXL for keratoconus.

    Results: A difference in corneal hysteresis between the control group and the patients with keratoconus was found at baseline, both with an applanation resonance tonometer (ART) and an ocular response analyzer (ORA), at mean (SD) values of -1.09 (1.92) mm Hg (99% CI, -2.26 to 0.07; P = .01) and -2.67 (2.55) mm Hg (99% CI, -4.05 to -1.32; P < .001), respectively. Increased corneal hysteresis was demonstrated with an ART 1 and 6 months after CXL, at 1.2 (2.4) mm Hg (99% CI,-0.1 to 2.5; P = .02) and 1.1 (2.7) mm Hg (99% CI, -0.3 to 2.6; P = .04), respectively, but not with ORA. A decrease in corneal thickness was seen 1 and 6 months after treatment (-24 [26] µm, P < .001; and -11 [21] µm, P = .01, respectively), and a corneal flattening of -0.6 (0.7) diopters was seen at 6 months (P < .001). No significant change in intraocular pressure was identified in patients with keratoconus with any method, except for an increase at 1 month with Goldmann applanation tonometry (P = .005).

    Conclusions and Relevance: To our knowledge ART is the first in vivo method able to assess the increased corneal hysteresis after CXL treatment. Given the large-scale use of CXL in modern keratoconus treatment, a tool with this capacity has a great potential value. Refinement of the ART method of measuring and quantifying corneal biomechanical properties will be a subject of further studies.

  • 183.
    Beckman Rehnman, Jeannette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Behndig, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Initial results from mechanical compression of the cornea during crosslinking for keratoconus2014Inngår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, nr 7, s. 644-649Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea.

    Methods: In a prospective, open, randomized case-control study conducted at the Department of Ophthalmology, Umeå University Hospital, Sweden, sixty eyes of 43 patients with progressive keratoconus aged 18-28 years planned for corneal crosslinking and corresponding age- and sex-matched control subjects were included. The patients were randomized to conventional corneal crosslinking (CXL; n = 30) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment (CRXL; n = 30). Subjective refraction and ETDRS best spectacle-corrected visual acuity (BSCVA), axial length measurement, keratometry and pachymetry were performed before and 1 and 6 months after treatment.

    Results: The keratoconus patients had poorer BSCVA, higher refractive astigmatism and higher keratometry readings than the control subjects at baseline (p < 0.01). In the CXL group, BSCVA increased from 0.19 ± 0.26 to 0.14 ± 0.18 logMar (p = 0.03), and the spherical equivalent improved from -1.9 ± 2.8 D to -1.4 ± 2.4 D (p = 0.03). Maximum keratometry readings decreased after CXL from 53.1 ± 4.9 D to 52.6 ± 5.2 D (p = 0.02), and the axial length decreased in the CXL group, likely due to post-treatment corneal thinning (p = 0.03). In the CRXL group, all the above variables were unaltered (p > 0.05).

    Conclusion: At 6 months, the refractive results from CRXL did not surpass those of conventional CXL treatment. Rather, some variables indicated a slightly inferior effect. Possibly, stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens.

  • 184.
    Beckman Rehnman, Jeannette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Behndig, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols: A Randomized Clinical Trial2015Inngår i: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 133, nr 11, s. 1254-1260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Importance: We describe and evaluate a complementary method to indirectly quantify the treatment effect of corneal cross-linking (CXL). Additional methods to indirectly quantify the treatment effect of CXL are needed.

    Objective: To assess the spatial distribution and the time course of the increased corneal densitometry (corneal light backscatter) seen after CXL with riboflavin and UV-A irradiation.

    Design, Setting, and Participants: Open-label randomized clinical trial of 43 patients (60 eyes) who were 18 to 28 years of age and had progressive keratoconus and a plan to be treated with CXL at Umeå University Hospital, Umeå, Sweden. The patients were randomized to receive conventional CXL (n = 30) using the Dresden protocol or CXL with mechanical compression of the cornea using a flat rigid contact lens sutured to the cornea during the treatment (CRXL) (n = 30). All participants were followed up during a 6-month period from October 13, 2009, through May 31, 2012.

    Interventions: Corneal cross-linking according to the Dresden protocol or CRXL.

    Main Outcomes and Measures: Change in corneal densitometry after CXL and CRXL for keratoconus.

    Results: Of the original 60 eyes included, 4 had incomplete data. A densitometry increase was seen after both treatments that was deeper and more pronounced in the CXL group (difference between the groups at 1 month in the center layer, zone 0-2 mm, 5.02 grayscale units [GSU], 95% CI, 2.92-7.12 GSU; P < .001). This increase diminished with time but was still noticeable at 6 months (difference between the groups at 6 months in the center layer, zone 0-2 mm, 3.47 GSU; 95% CI, 1.72-5.23 GSU; P < .001) and was proportional to the reduction in corneal steepness (R = -0.45 and -0.56 for CXL and CRXL, respectively).

    Conclusions and Relevance: The degree of corneal light backscatter relates to the reduction in corneal steepness after cross-linking and may become a relevant complement to other methods in evaluating the cross-linking effect, for example, when comparing different treatment regimens.

    Trial Registration: clinicaltrials.gov Identifier: NCT02425150.

  • 185.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014Inngår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 11, artikkel-id 22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

  • 186.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.2010Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, nr 6, s. 1050-1057Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

  • 187.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Intracranial Pressure and Pulsatility Index:  2011Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, nr 4, s. E1033-E1034Artikkel i tidsskrift (Fagfellevurdert)
  • 188.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 4, s. 233-241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 189. Belitskaya-Lévy, Ilana
    et al.
    Zeleniuch-Jacquotte, Anne
    Russo, Jose
    Russo, Irma H
    Bordás, Pal
    Ahman, Janet
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Li, Xiaochun
    de Cicco, Ricardo López
    Peri, Suraj
    Ross, Eric
    Russo, Patricia A
    Santucci-Pereira, Julia
    Sheriff, Fathima S
    Slifker, Michael
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Toniolo, Paolo
    Arslan, Alan A
    Characterization of a genomic signature of pregnancy identified in the breast2011Inngår i: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 4, nr 9, s. 1457-1464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

  • 190.
    Benedek, Hunor
    et al.
    Skåne University Hospital, Lund, Sweden.
    Isacsson, Ulf
    Uppsala University Hospital, Uppsala, Sweden .
    Olevik-Dunder, Maria
    Karolinska University Hospital, Stockholm, Sweden.
    Westermark, Mathias
    Karolinska University Hospital, Stockholm, Sweden.
    Hållström, Per
    Gävle Hospital, Gavle, Swe.
    Olofsson, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Gustafsson, Magnus
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Strategies for quality assurance of intensity modulated radiation therapy2015Inngår i: 8TH INTERNATIONAL CONFERENCE ON 3D RADIATION DOSIMETRY (IC3DDOSE), Institute of Physics (IOP), 2015, Vol. 573, s. 012015-, artikkel-id 012015Konferansepaper (Fagfellevurdert)
    Abstract [en]

    In late 2011 The Swedish Society of Radiation Physics formed a working group to concentrate on the Quality Assurance of modern radiation therapy techniques. The given task was to identify and summarise the different QA strategies in Sweden and also the international recommendations. This was used to formulate recommendations for practical guidelines within Sweden. In this paper a brief summery of the group's work is presented. All the Swedish radiation therapy centres do a pre treatment verification measurement as QA for every new IMRT and VMAT plan. Physicists do it and they believe it to be time consuming. A general standpoint from all the centres was that new guidelines and legislation is needed to allow QA that does not require a measurement. Based on various international publications and recommendations the working group has presented two strategies, one where all new plans are checked through measurement and one where no measurement is needed. The measurement-based strategy is basically the same as the one used today with an extended machine QA part. The other presented strategy is process oriented where all the different parts of the treatment chain are checked separately. The final report can be found in Swedish on http://www.radiofysik.org.

  • 191. Bengtsson, Daniel
    et al.
    Joost, Patrick
    Aravidis, Christos
    Stenmark, Marie Askmalm
    Backman, Ann-Sofie
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    von Salome, Jenny
    Zagoras, Theofanis
    Gebre-Medhin, Samuel
    Burman, Pia
    Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort2017Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, nr 11, s. 3928-3932Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported.

    Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient’s germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS.

    Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected).

    Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

  • 192.
    Bengtsson Ågren, Elsa
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rehabilitation needs before, during and after adjuvant chemotherapy2017Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 193.
    Bennmar, Zandra
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Obotligt cancersjuk i norra regionens glesbygd. En retrospektiv jämförelse mellan länen avseende dödsplats och palliativt vårdinnehåll.2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 194.
    Bergdahl, Ingvar A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Eriksson, Kåre
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Damber, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Järvholm, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lung cancer and exposure to quartz and diesel exhaust in Swedish iron ore miners with concurrent exposure to radon2010Inngår i: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 67, nr 8, s. 513-518Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Studies of underground miners have documented an increased risk of lung cancer mainly linked to radon exposure but possibly influenced by other concurrent exposures. METHODS: A cohort study was carried out in 8321 iron ore miners with low exposure to radon, employed in 1923-1998 and followed up for lung cancer in 1958-2000. Historical exposures to radon, crystalline silica and diesel exhaust were assessed. Data including exposure to radon, quartz and diesel exhaust from another mine with higher exposure to radon were reanalysed. RESULTS: Miners had increased risk for lung cancer (SIR 1.48 (95% CI 1.22 to 1.78), based on 112 cases during 227,000 person-years). The increased risk could not be explained by exposure to radon or diesel exhaust but was associated with exposure to crystalline silica: SIR 0.96 (0.53 to 1.62), 1.45 (1.10 to 1.87), 1.99 (1.31 to 2.90) and 1.77 (0.92 to 3.10) in groups with exposure to 0, 0-2, 2-5 and >5 mg years/m3, respectively. Reanalysis of data from the other mine indicated that quartz was a possible confounder in the analysis of relationship between radon and lung cancer. In the highest radon exposed group, the point estimate for the RR decreased from 5.65 to 3.90 when adjusting for concurrent exposure to quartz. CONCLUSIONS: Crystalline silica, a known carcinogen, probably affects lung cancer risk in iron ore miners. The main implication of the results is for interpretation of the dose-response curve for radon and lung cancer in underground iron ore miners. Since exposure to radon and quartz is often correlated, quartz exposure can be an important confounder.

  • 195.
    Bergdahl, Jan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Lars-Göran
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Treatment of chronic stress in employees: subjective, cognitive and neural correlates2005Inngår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 46, nr 5, s. 395-402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N= 27) and control (N= 23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

  • 196. Bergdahl, Maud
    et al.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Psykologiska institutionen, Stockholms universitet.
    Difference in apolipoprotein E type 4 allele (APOE e4) amongdentate and edentulous subjects2008Inngår i: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 25, nr 3, s. 179-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To evaluate the frequency of apolipoprotein (APOE) alleles and determine whether APOE type 4 allele (e4) was associated with edentulousness even when certain factors were controlled.Background: The APOE are important in lipid homeostasis, and APOE e4 has been found in many diseases and to have a negative impact on longevity. Tooth loss is more common in ill aged subjects with low income and education.Materials and methods: In a population-based study involving 1860 subjects between 35 and 85 years 1321 dentate (mean age = 54; 54% women, 46% men) and 539 edentulous (mean age = 72; 62% women, 38% men) subjects were studied. Logistic regression was performed with dentate/edentulous as dependent variables and years of education, socio-economic status, social network, stress level, handicap from birth, 23 various diseases and APOE e4 as covariates. Thereafter, APOE e4 frequencies were studied in 342 dentateand 336 edentulous subjects 50–85 years of age. The subjects were matched with regard to age, gender, years of education, living condition, stress level, handicap from birth and 23 various diseases.Results: APOE allele frequency in the total group was e2 = 7.8%, e3 = 76.4% and e4 = 15.8%. Age, living condition, years of education and APOE e4 were significant covariates in edentulous subjects (p £ 0.001).APOE e4 in the matched groups revealed significant differences between the dentate group and the edentulous group (v2 = 5.68; p = 0.017). There was no group effect (F(29,648) = 0.849; p < 0.696; Wilks’ lambda = 0.963). In the dentate group, the frequencies of APOE were: e2 = 8.8%, e3 = 77.9% ande4 = 13.3%. Corresponding frequencies of APOE in the edentulous group were: e2 = 6.6%, e3 = 75.4% and e4 = 18.0%.Conclusion: Despite matching both groups with regard to different background factors, the edentulous group had a higher frequency of APOE e4 than the dentate group. Thus, genetic factors might contribute to greater risk in developing complex oral diseases leading to tooth loss or just be an indication that the subjects in our study carrying APOE e4 are more fragile.

  • 197. Bergdahl, Maud
    et al.
    Habib, Reza
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nilsson, Lars-Göran
    Natural teeth and cognitive function in humans2007Inngår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 48, nr 6, s. 557-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A number of neurobiological, psychological and social factors may account for cognitive impairment. In animal studies a relation between dental status and cognitive performance has been found. It is unclear whether such a relation exists for humans. In a first step we compared the performance of 1,351 participants (53% women, 47% men; age M = 54.0) with natural teeth to 487 edentulous participants (59% women, 41% men; age M = 71.3) on 12 cognitive tests. The natural teeth group had a lower mean age, fewer women, more years of education, higher mini-mental state (MMSE), and performed significantly higher on several cognitive tests. In a subsequent analysis, the cognitive performance of a subset of the participants (50–85 years) was examined. In this analysis, 211 had natural dentition and 188 were edentulous. The groups were matched for gender, age, social variables, diseases, stress and MMSE. The cognitive disadvantage of the edentulous group was still apparent. The results suggest that functional natural teeth relate to relatively preserved cognitive functioning in older age.

  • 198.
    Bergenheim, A Tommy
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Capala, Jacek
    Roslin, Michael
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Distribution of BPA and metabolic assessment in glioblastoma patients during BNCT treatment: a microdialysis study2005Inngår i: J Neurooncol, ISSN 0167-594X, Vol. 71, nr 3, s. 287-293Artikkel i tidsskrift (Fagfellevurdert)
  • 199.
    Bergenheim, A Tommy
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Roslin, Michael
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Ungerstedt, Urban
    Waldenström, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Ronquist, Gunnar
    Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).2006Inngår i: J Neurooncol, ISSN 0167-594X, Vol. 80, nr 3, s. 285-293Artikkel i tidsskrift (Fagfellevurdert)
  • 200. Bergenheim, M
    et al.
    Johansson, H
    Pedersen, J
    Öhberg, Fredrik
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper.
    Sjölander, P
    Ensamble coding of muscle stretches in afferent populations containing different types of muscle afferents1996Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 734, nr 1-2, s. 157-166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ensemble coding of simple mechanical stimuli (small sinusoidal stretches) was studied in simultaneously recorded mixed ensembles of primary- and secondary muscle spindle afferents (MSAs), and Golgi tendon organ (GTO) afferents recorded from L7-S1 dorsal root filaments. The experiments were made on 48 recorded afferents (29 primary MSAs, 6 secondary MSAs and 13 GTO afferents) in chloralose anaesthetised cats. For the analyses, we used a combination of principal component analysis and algorithms for quantification of stimulus discrimination. Mixed ensembles of primary- and secondary MSAs, and GTO afferents, discriminated significantly better between different muscle stretches than ensembles of only one or two types of these afferents. All kinds of ensembles showed a successive increase in discriminative ability with increased ensemble size, and this ability seemed to level at larger populations. However, the increase in discriminative ability was significantly greater for the mixed ensembles. It is hypothesised that the main reason for the greater discriminative ability achieved by mixed ensembles, might be that the variation in response profiles (sensitivity tuning) among the individual afferents of the mixed ensemble will be larger than that for ensembles of only one type of afferent. Finally, the results in the present study give experimental support to some of the teleological arguments in favour of the ensemble coding theory.

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