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  • 201.
    Bergenheim, Tommy
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malmström, Annika
    Bolander, Hans
    Michanek, Annika
    Stragliotto, Giuseppe
    Damber, Lena
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Björ, Ove
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Registrering av primära hjärntumörer mått på nationell vårdkvalitet. Regionala skillnader avslöjade.2007Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, nr 5, s. 332-341Artikkel i tidsskrift (Fagfellevurdert)
  • 202. Berger, Eloise
    et al.
    Delpierre, Cyrille
    Hosnijeh, Fatemeh Saberi
    Kelly-Irving, Michelle
    Portengen, Lutzen
    Bergdahl, Ingvar
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Ann Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Kyrtopoulos, Soterios A.
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Vermeulen, Roel
    Castagné, Raphaële
    Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 10805Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and.-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β= -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.

  • 203. Bergfelt, E.
    et al.
    Kozlowski, P.
    Ahlberg, L.
    Hulegardh, E.
    Hagglund, H.
    Karlsson, K.
    Markuszewska-Kuczymska, Alicja
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Tomaszewska-Toporska, B.
    Smedmyr, B.
    Astrom, M.
    Amini, R. M.
    Hallbook, H.
    MINIMAL RESIDUAL DISEASE IN ADULTS WITH PHILADELPHIA NEGATIVE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA A SWEDISH POPULATION-BASED STUDY2014Inngår i: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, nr 1 (suppl), s. 279-280Artikkel i tidsskrift (Annet vitenskapelig)
  • 204. Berggren, Daniel Moreno
    et al.
    Folkvaljon, Yasin
    Engvall, Marie
    Sundberg, Johan
    Lambe, Mats
    Antunovic, Petar
    Garelius, Hege
    Lorenz, Fryderyk
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nilsson, Lars
    Rasmussen, Bengt
    Lehmann, Sören
    Hellström-Lindberg, Eva
    Jädersten, Martin
    Ejerblad, Elisabeth
    Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register2018Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, nr 5, s. 614-627Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2.9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0.05) and for WPSS compared to IPSS (P=0.07). IPSS-R was superior to both IPSS and WPSS for patients aged <= 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

  • 205. Berggrund, Malin
    et al.
    Enroth, Stefan
    Lundberg, Martin
    Assarsson, Erika
    Stålberg, Karin
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Olovsson, Matts
    Gyllensten, Ulf
    Identification of candidate plasma protein biomarkers for cervical cancer using the multiplex proximity extension assay2019Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, nr 4, s. 735-743, artikkel-id RA118.001208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared to controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared to population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

  • 206.
    Bergh, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Marklund, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Gustavsson, C
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wiklund, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grönberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Alexeyev, Olog
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    No link between viral findings in the prostate and subsequent cancer development2007Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, nr 1, s. 137-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

  • 207.
    Bergh, Johanna
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Marklund, Ingrid
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Virologi.
    Thellenberg-Karlsson, Camilla
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Grönberg, Henrik
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Elgh, Fredrik
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Alexeyev, Oleg A
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Detection of Escherichia coli 16S RNA and Cytotoxic Necrotizing Factor 1 Gene in Benign Prostate Hyperplasia.2007Inngår i: Eur Urol, ISSN 0302-2838, Vol. 51, nr 2, s. 457-463Artikkel i tidsskrift (Fagfellevurdert)
  • 208. Bergh, Jonas C. S.
    et al.
    Andersson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bjohle, Judith
    Bosch, Ana
    Carlsson, Lena
    Dreifaldt, Ann Charlotte
    Einbeigi, Zakaria
    Fredholm, Hanna
    Isaksson-Friman, Erika
    Foukakis, Theodoros
    Elinder, Ellinor
    Hellstrom, Mats
    Johansson, Hemming
    Lekberg, Tobias
    Lindman, Henrik
    Maes, Claudia
    Brandberg, Yvonne
    Hatschek, Thomas
    Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer: results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard?2019Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 15, s. 501-501Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Neoadjuvant therapy produces high rates of pathological complete response (pCR) and is the standard of care in HER2 positive breast cancer; however, the optimal treatment regimen remains to be established. Methods: In this randomized phase II study patients ≥18 years with HER2 positive breast cancer > 20mm or verified lymph node metastases were randomized to 6 courses of docetaxel, trastuzumab and pertuzumab (DTP, group A) or trastuzumab emtansine (T-DM1, group B), q 21 days. The protocol allowed switch to the competing treatment upon lack of response or drug-related severe toxicity. Patients received postoperative epirubicin+cyclophosphamide, trastuzumab for a total of one year and endocrine therapy. Accrual was completed in October 2018 after randomization of 202 patients, data on pCR were available for 190 at the time for this abstract submission. Median age, 52 years (26-74), menopausal status, histological type and grade were well balanced between the treatment groups. 62.6% of the tumors were hormone receptor (HR) positive. Results: Primary endpoint was pathological objective response. 190 patients completed the protocol-specified preoperative treatment. pCR was achieved in 45.3% of patients, 46.4% in patients treated with DTP and 44.1% with T-DM1 (chi-sq., p = 0.75). In HR-positive tumors, pCR was obtained in 35.3% of patients, 35.9% in group A vs. 34.6% in group B (p = 0.87); in HR-negative tumors, the overall pCR rate was 62.0%, 66.7% in group A vs. 57.9% in group B (p = 0.45). Severe (grade 3/4) toxicity was reported at 68 occasions related to DTP, compared with 16 related to T-DM1, 26 vs. 3 caused by febrile neutropenia. Significantly better quality of life was reported by patients treated with T-DM1. Conclusions: Our data on TDM-1 demonstrates similar efficacy and less toxicity, in particular for patients with HER2 and HR positive cancers, being a potential new standard for neoadjuvant therapy. Clinical trial information: NCT02568839.

  • 209. Bergh, Jonas
    et al.
    Jönsson, Per-Ebbe
    Lidbrink, Elisabet Kerstin
    Trudeau, Maureen
    Eiermann, Wolfgang
    Brattström, Daniel
    Lindemann, Justin P O
    Wiklund, Fredrik
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    FACT: An Open-Label Randomized Phase III Study of Fulvestrant and Anastrozole in Combination Compared With Anastrozole Alone as First-Line Therapy for Patients With Receptor-Positive Postmenopausal Breast Cancer2012Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 16, s. 1919-1925Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer.

    Patients and Methods: Postmenopausal women, or premenopausal women receiving a gonadotropin-releasing hormone agonist, with estrogen receptor– and/or progesterone receptor–positive disease at first relapse after primary treatment of localized disease were open-label randomly assigned to a fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone. The primary end point was time to progression (TTP).

    Results: In all, 514 women were randomly assigned to fulvestrant plus anastrozole (experimental arm; n = 258) or anastrozole (standard arm; n = 256). Approximately two thirds had received adjuvant antiestrogens, but only eight individuals had received an aromatase inhibitor. Median TTP was 10.8 and 10.2 months in the experimental versus standard arm, respectively (hazard ratio [HR] = 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was 37.8 and 38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00). Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023). Death owing to AEs was reported in 11 (4.3%) and five patients (2.0%) in the experimental versus standard arm, respectively.

    Conclusion: Fulvestrant (250 mg + LD regimen) in combination with anastrozole offered no clinical efficacy advantage over anastrozole monotherapy in this population of individuals with a relatively high proportion of previous adjuvant antiestrogen exposure.

  • 210.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning2018Inngår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, nr 4, s. 266-274Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

    Setting: Neurorehabilitation clinic.

    Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

    Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

    Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

    Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

  • 211.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway Medicine.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. School of Sport Sciences, The Arctic University of Norway, Tromsø, Norway.
    Pharmaco-fMRI in Patients With Traumatic Brain Injury: A Randomized Controlled Trial With the Monoaminergic Stabilizer (-)-OSU61622019Inngår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 34, nr 3, s. 189-198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To examine the effects of monoaminergic stabilizer (-)-OSU6162 on brain activity, as measured by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients in the chronic phase of traumatic brain injury suffering from fatigue.

    SETTING: Neurorehabilitation clinic.

    PARTICIPANTS: Patients with traumatic brain injury received either placebo (n = 24) or active treatment (n = 28). Healthy controls (n = 27) went through fMRI examination at one point and were used in sensitivity analysis on normalization of BOLD response.

    DESIGN: Randomized, double-blinded, placebo-controlled design.

    MAIN MEASURES: Effects on BOLD signal changes from before to after treatment during performance of a fatiguing attention task.

    RESULTS: The fMRI results revealed treatment effects within the right occipitotemporal cortex and the right orbitofrontal cortex. In these regions, the BOLD response was normalized relative to healthy controls at the postintervention fMRI session. No effects were seen in regions in which we previously observed activity differences between patients and healthy controls while performing this fMRI task, such as the striatum.

    CONCLUSION: (-)-OSU6162 treatment had influences on functional brain activity, although the normalized regional BOLD response was observed in regions that were not a priori hypothesized to be sensitive to this particular treatment, and was not accompanied by any effects on in-scanner test performance or on fatigue.

  • 212.
    Berglin, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lorentzon, Ronnie
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Nordmark, L
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson-Sojka, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Predictors of radiological progression and changes in hand bone density in early rheumatoid arthritis2003Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 42, nr 2, s. 268-275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To identify predictors for radiological and functional outcome and bone loss in the hands in early rheumatoid arthritis (RA) during the first 2 yr of disease and to study the relationship between these variables.

    METHODS: An inception cohort of consecutively recruited patients was examined at baseline and after 12 and 24 months using X-rays of hands and feet, clinical [28-joint count, Health Assessment Questionnaire (HAQ), global visual analogue scale (VAS), grip strength] and laboratory (erythrocyte sedimentation rate, C-reactive protein, markers of bone formation and resorption) measurements and dual-energy X-ray absorptiometry measurements of the hands.

    RESULTS: Joint destruction increased significantly during the study, with the Larsen score at baseline as the strongest predictor. Radiological progression and bone loss over 24 months were significantly retarded in patients responding to therapy. The effects of the shared epitope and initial high inflammatory activity on radiological progression were overridden by the therapeutic response. Radiological progression correlated significantly with bone loss. Global VAS, Larsen score and HAQ at inclusion significantly predicted change in HAQ over time.

    CONCLUSIONS: Radiological progression and bone loss were retarded by early therapeutic response. Bone loss was related to radiological progression.

  • 213. Berglund, Johan
    et al.
    Skorpil, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Multi-scale graph-cut algorithm for efficient water-fat separation2017Inngår i: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 78, nr 3, s. 941-949Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To improve the accuracy and robustness to noise in water-fat separation by unifying the multiscale and graph cut based approaches to B0 -correction.

    METHODS: A previously proposed water-fat separation algorithm that corrects for B0 field inhomogeneity in 3D by a single quadratic pseudo-Boolean optimization (QPBO) graph cut was incorporated into a multi-scale framework, where field map solutions are propagated from coarse to fine scales for voxels that are not resolved by the graph cut. The accuracy of the single-scale and multi-scale QPBO algorithms was evaluated against benchmark reference datasets. The robustness to noise was evaluated by adding noise to the input data prior to water-fat separation.

    RESULTS: Both algorithms achieved the highest accuracy when compared with seven previously published methods, while computation times were acceptable for implementation in clinical routine. The multi-scale algorithm was more robust to noise than the single-scale algorithm, while causing only a small increase (+10%) of the reconstruction time.

    CONCLUSION: The proposed 3D multi-scale QPBO algorithm offers accurate water-fat separation, robustness to noise, and fast reconstruction. The software implementation is freely available to the research community. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

  • 214. Berglund, Mattias
    et al.
    Enblad, Gunilla
    Thunberg, Ulf
    Amini, Rose-Marie
    Sundström, Christer
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Erlanson, Martin
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Rosenquist, Richard
    Larsson, Catharina
    Lagercrantz, Svetlana
    Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.2007Inngår i: Modern Patholology, ISSN 0893-3952, Vol. 20, nr 1, s. 63-75Artikkel i tidsskrift (Fagfellevurdert)
  • 215. Bergman, Annika
    et al.
    Sahlin, Pelle
    Emanuelsson, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Carén, Helena
    Tarnow, Peter
    Martinsson, Tommy
    Grönberg, Henrik
    Stenman, Göran
    Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer.2009Inngår i: Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi, ISSN 1651-2073, Vol. 43, nr 5, s. 251-255Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.

  • 216.
    Bergman, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mattson-Frost, Tove
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Levine, James
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Installing treadmill workstations in offices does little for cognitive performance and brain structure, despite a baseline association between sitting time and hippocampus volumeManuskript (preprint) (Annet vitenskapelig)
  • 217.
    Bergman, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wahlström, Viktoria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lanthén, Ellen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Renklint, Rebecka
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Levine, James A.
    Department of Endocrinology, The Mayo Clinic, Rochester, MN, USA; Fondation IPSEN, Paris, France.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial2018Inngår i: The Lancet Public Health, ISSN 2468-2667, Vol. 3, nr 11, artikkel-id e523-e535Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time.

    Methods: We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants.

    Findings: Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon.

    Interpretation: In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity.

  • 218. Bergouignan, Loretxu
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ehrsson, H. Henrik
    Out-of-body-induced hippocampal amnesia2014Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, nr 12, s. 4421-4426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed similar to 1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

  • 219. Bergqvist, Jenny
    et al.
    Iderberg, Hanna
    Mesterton, Johan
    Bengtsson, Nils
    Wettermark, Bjorn
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Regional Cancer Centre Stockholm-Gotland, Stockholm County Council, Stockholm, Sweden.
    Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors: a Swedish population-based register study2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 3, s. 405-414Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated.

    Materials and methods: A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process.

    Results: High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level.

    Conclusions: Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

  • 220. Bergqvist, Jenny
    et al.
    Iderberg, Hanna
    Mesterton, Johan
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Regional Cancer Centre Stockholm Gotland, Stockholm County Council, Stockholm, Sweden.
    The effects of clinical and sociodemographic factors on survival, resource use and lead times in patients with high-grade gliomas: a population-based register study2018Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 139, nr 3, s. 599-608Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Previous studies indicate an effect of sociodemographic factors on risk for being diagnosed with, as well as on survival of cancer in general. Our primary aim was to analyse sociodemographic factors, resource use and lead times in health care after diagnosis with high grade malignant glioma (HGG) in a large population based cohort.

    Methods: A register-based study using several unique high-coverage registries. All patients over the age of 18 diagnosed with HGG in the Swedish Stockholm-Gotland region between 2001 and 2013 (n=1149) were included.

    Results: In multivariable cox proportional hazard model of survival, older age, male sex and high tumour grade were associated with worse survival. No significant differences could be seen related to country of birth. A high disposable income was associated with better survival and fewer occasions of pre-diagnostic inpatient care. Older age and comorbidities were correlated with a significantly increased number of outpatient visits the year before HGG diagnosis. In addition, male sex, being born outside Sweden was associated to a higher number of outpatient visits the year after diagnosis in multivariable analysis. Leadtime from diagnosis (first suspicion on brain scan) to surgery showed that the oldest patients, patients with comorbidity and patients born outside Europe had to wait longer for surgery.

    Conclusions: Sociodemographic factors like education, income and country of birth have impact on care processes both before and after the diagnosis HGG. This needs to be acknowledged in addition to important clinical factors like age, comorbidity and tumour grade, in order to accomplish more equal cancer care.

  • 221.
    Bergqvist, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Christensen, H. Nordahl
    Wiklund, F.
    Bergström, S.
    Characteristics and Long-Term OS of Non-Small Cell Lung Cancer Patients Receiving EGFR Tyrosine Kinase Inhibitor Treatment2018Inngår i: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, nr 10, s. S419-S419Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are important therapeutic agents in treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. However, long-term follow-up and knowledge of clinical factors and TKI treatment patterns, which may be associated with longer OS, remains unclear. Using nationwide registry data, the aim was to investigate survival, prognostic factors for OS, and first line TKI treatment pattern of stage IIIB/IV NSCLC patients in Sweden.

    Method: In this cohort study, data on all patients diagnosed with stage IIIB-IV NSCLC during 2010—2015 from the nationwide Cancer Registry of Sweden were linked with data on dispensed EGFR-TKI drugs, comorbidity, and mortality data from Swedish national health registries. OS was defined as the interval from date of diagnosis until date of death. Survival rates were estimated using the Kaplan-Meier method. Assessment of predictive factors for OS was performed in multivariable Cox regression.

    Result: Of 9,992 stage IIIB/IV NSCLC patients (mean age 70 years, female 49%), 1419 (14%) received first-line TKI treatment. Overall, 59% of TKI treated patients (median age 68 years) were female, 44% had at least one comorbidity, 85% had adenocarcinoma, and 89% were stage IV. Median follow-up time was 15 months and median OS was 16 months; 1- and 3-years survival rates were 62% and 15%, respectively. Predictors of longer OS were younger age at diagnosis, adenocarcinoma, less advanced clinical stage, and less comorbid disease. Furthermore, patients included in the end of the period had a longer OS compared to earlier. TKI treatment switching/re-challenging, as well as prolonged TKI treatment, also predicted longer OS.

    Conclusion: This is the first nationwide study on NSCLC patients receiving first-line EGFR TKIs in routine clinical practice in Sweden. In addition to the reported prolonged TKI treatment length and TKI switching/re-challenging during the observation period, improvements and extension of EGFR testing targeting the appropriate NSCLC patient population may further have contributed to the observed relatively long overall survival.

  • 222.
    Bergqvist, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Center for Research & Development, Uppsala University, County Council of Gävleborg, Gävle Hospital, Gävle, Sweden.
    Christensen, Helene N.
    Wiklund, Fredrik
    Bergström, Stefan
    Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010-2016 in Sweden: A nationwide observational study2019Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB-IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010-2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less >= 1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010-2011; 14.4 months 2012-2013; 18.6 months 2014-2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.

  • 223. Bergqvist, Michael
    et al.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Brattström, Daniel
    Novel agents in the treatment of non-small cell lung cancer: implications for neoadjuvant chemotherapy?2005Inngår i: In Vivo, ISSN 0258-851X, Vol. 19, nr 3, s. 523-533Artikkel i tidsskrift (Fagfellevurdert)
  • 224.
    Bergqvist, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Gävle Hospital, Center for Research & Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden.
    Holgersson, Georg
    Bondarenko, Igor
    Grechanaya, Elena
    Maximovich, Alexey
    Andor, Gyorgy
    Klockare, Maria
    Thureson, Marcus
    Jerling, Markus
    Harmenberg, Johan
    Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 3, s. 441-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).

    Material and methods: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m2 in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.

    Results: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.

    Conclusion: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

  • 225. Bergström, S.
    et al.
    Christensen, H. Nordahl
    Wiklund, F.
    Bergqvist, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    EGFR tyrosine kinase inhibitors in non-small cell lung cancer: Nationwide register-based cohort study in Sweden2018Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, s. 526-526Artikkel i tidsskrift (Annet vitenskapelig)
  • 226. Berntsson, Shala G.
    et al.
    Merrell, Ryan T.
    Amirian, E. Susan
    Armstrong, Georgina N.
    Lachance, Daniel
    Smits, Anja
    Zhou, Renke
    Jacobs, Daniel I.
    Wrensch, Margaret R.
    Olson, Sara H.
    Il'yasova, Dora
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Schildkraut, Joellen
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S.
    Jenkins, Robert B.
    Bernstein, Jonine L.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Bondy, Melissa L.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study2018Inngår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, nr 6, s. 1432-1442Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.

    Methods: The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures.

    Results: Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.

    Conclusions: Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

  • 227. Berntsson, Shala Ghaderi
    et al.
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bondy, Melissa
    Qu, Mingqi
    Smits, Anja
    Tumor-associated epilepsy and glioma: Are there common genetic pathways?2009Inngår i: Acta oncologica (Stockholm, Sweden), ISSN 1651-226X, Vol. 48, nr 7, s. 955-963Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

  • 228. Berntsson, Shala Ghaderi
    et al.
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sjöström, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Broholm, Helle
    Johansson, Christoffer
    Fleming, Sarah J
    McKinney, Patricia A
    Bethke, Lara
    Houlston, Richard
    Smits, Anja
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Melin, Beatrice S
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas2011Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 105, nr 3, s. 531-538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.

  • 229. Berthon, B.
    et al.
    Häggström, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Apte, A.
    Beattie, B.
    Kirov, A.
    Humm, J.
    Marshall, C.
    Spezi, E.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Schmidtlein, C.
    A Fast Positron Emission Tomography Simulator for Synthetic Lesion Simulation2014Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, nr 2, s. S367-S367Artikkel i tidsskrift (Annet vitenskapelig)
  • 230.
    Berthon, Beatrice
    et al.
    Wales Research and Diagnostic PET Imaging Centre, Cardiff University, Cardiff, UK.
    Häggström, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Apte, Aditya
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    Beattie, Bradley J.
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    Kirov, Assen S.
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    Humm, John L.
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    Marshall, Christopher
    Wales Research and Diagnostic PET Imaging Centre, Cardiff University, Cardiff, UK.
    Spezi, Emiliano
    School of Engineering, Cardiff University, Cardiff, Wales, UK.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Schmidtlein, C. Ross
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    PETSTEP: generation of synthetic PET lesions for fast evaluation of segmentation methods2015Inngår i: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 31, nr 8, s. 969-980Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: This work describes PETSTEP (PET Simulator of Tracers via Emission Projection): a faster and more accessible alternative to Monte Carlo (MC) simulation generating realistic PET images, for studies assessing image features and segmentation techniques.

    Methods: PETSTEP was implemented within Matlab as open source software. It allows generating threedimensional PET images from PET/CT data or synthetic CT and PET maps, with user-drawn lesions and user-set acquisition and reconstruction parameters. PETSTEP was used to reproduce images of the NEMA body phantom acquired on a GE Discovery 690 PET/CT scanner, and simulated with MC for the GE Discovery LS scanner, and to generate realistic Head and Neck scans. Finally the sensitivity (S) and Positive Predictive Value (PPV) of three automatic segmentation methods were compared when applied to the scanner-acquired and PETSTEP-simulated NEMA images.

    Results: PETSTEP produced 3D phantom and clinical images within 4 and 6 min respectively on a single core 2.7 GHz computer. PETSTEP images of the NEMA phantom had mean intensities within 2% of the scanner-acquired image for both background and largest insert, and 16% larger background Full Width at Half Maximum. Similar results were obtained when comparing PETSTEP images to MC simulated data. The S and PPV obtained with simulated phantom images were statistically significantly lower than for the original images, but led to the same conclusions with respect to the evaluated segmentation methods.

    Conclusions: PETSTEP allows fast simulation of synthetic images reproducing scanner-acquired PET data and shows great promise for the evaluation of PET segmentation methods.

  • 231. Best, Myron G.
    et al.
    Sol, Nik
    Kooi, Irsan
    Tannous, Jihane
    Westerman, Bart A.
    Rustenburg, Francois
    Schellen, Pepijn
    Verschueren, Heleen
    Post, Edward
    Koster, Jan
    Ylstra, Bauke
    Ameziane, Najim
    Dorsman, Josephine
    Smit, Egbert F.
    Verheul, Henk M.
    Noske, David P.
    Reijneveld, Jaap C.
    Nilsson, R. Jonas A.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Tannous, Bakhos A.
    Wesseling, Pieter
    Wurdinger, Thomas
    RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics2015Inngår i: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 28, nr 5, s. 666-676Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".

  • 232. Best, Myron G.
    et al.
    Sol, Nik
    't Veld, Sjors G. J. G. In
    Vancura, Adrienne
    Muller, Mirte
    Niemeijer, Anna-Larissa N.
    Fejes, Aniko V.
    Tjon Kon Fat, Lee-Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    't Veld, Anna E. Huis In
    Leurs, Cyra
    Le Large, Tessa Y.
    Meijer, Laura L.
    Kooi, Irsan E.
    Rustenburg, Francois
    Schellen, Pepijn
    Verschueren, Heleen
    Post, Edward
    Wedekind, Laurine E.
    Bracht, Jillian
    Esenkbrink, Michelle
    Wils, Leon
    Favaro, Francesca
    Schoonhoven, Jilian D.
    Tannous, Jihane
    Meijers-Heijboer, Hanne
    Kazemier, Geert
    Giovannetti, Elisa
    Reijneveld, Jaap C.
    Idema, Sander
    Killestein, Joep
    Heger, Michal
    de Jager, Saskia C.
    Urbanus, Rolf T.
    Hoefer, Imo E.
    Pasterkamp, Gerard
    Mannhalter, Christine
    Gomez-Arroyo, Jose
    Bogaard, Harm-Jan
    Noske, David P.
    Vandertop, W. Peter
    van den Broek, Daan
    Ylstra, Bauke
    Nilsson, Jonas A.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
    Wesseling, Pieter
    Karachaliou, Niki
    Rosell, Rafael
    Lee-Lewandrowski, Elizabeth
    Lewandrowski, Kent B.
    Tannous, Bakhos A.
    de Langen, Adrianus J.
    Smit, Egbert F.
    van den Heuvel, Michel M.
    Wurdinger, Thomas
    Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets2017Inngår i: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 32, nr 2, s. 238-252Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

  • 233.
    Best, Myron
    et al.
    VU Medical Center, Amsterdam, Netherlands.
    Sol, Nik
    VU Medical Center, Amsterdam, Netherlands.
    Kooi, Irsan
    VU Medical Center, Amsterdam, Netherlands.
    Nilsson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Westerman, Bart
    VU Medical Center, Amsterdam, Netherlands.
    Yistra, Bauke
    VU Medical Center, Amsterdam, Netherlands.
    Dorsman, Josephine
    VU Medical Center, Amsterdam, Netherlands.
    Smit, Egbert
    VU Medical Center, Amsterdam, Netherlands.
    Verheui, Henk
    VU Medical Center, Amsterdam, Netherlands.
    Reijneveld, Jaap
    VU Medical Center, Amsterdam, Netherlands.
    Tannous, Bakhos
    Massachusetts General Hospital, Boston, MA, USA.
    Wesseling, Pieter
    VU Medical Center, Amsterdam, Netherlands.
    Wurdinger, Thomas
    VU Medical Center, Amsterdam, Netherlands.
    Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer2015Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, nr Suppl. 15, artikkel-id LB-124Artikkel i tidsskrift (Annet vitenskapelig)
  • 234. Best, Myron
    et al.
    Sol, Nik
    Kooi, Irsan
    Nilsson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Westerman, Bart
    Ylstra, Bauke
    Dorsman, Josephine
    Smit, Egbert F
    Verheul, Henk M W
    Reijneveld, Jaap C
    Tannous, Bakhos A
    Wesseling, Pieter
    Wurdinger, Thomas
    Allowance of tumor-educated platelets for multiclass liquid biopsy-based diagnosis of cancer2015Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, nr 15, suppl., artikkel-id 11058Artikkel i tidsskrift (Annet vitenskapelig)
  • 235. Bethke, Lara
    et al.
    Murray, Anne
    Webb, Emily
    Schoemaker, Minouk
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Kosteljanetz, Michael
    Swerdlow, Anthony
    Houlston, Richard
    Comprehensive analysis of DNA repair gene variants and risk of meningioma2008Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, nr 4, s. 270-276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.

    Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.

    Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10−6; P = .009 after adjusting for multiple testing).

    Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.

  • 236. Bethke, Lara
    et al.
    Sullivan, Kate
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Swerdlow, Anthony
    Houlston, Richard
    CASP8 D302H and meningioma risk: an analysis of five case-control series2009Inngår i: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 273, nr 2, s. 312-315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.

  • 237. Bethke, Lara
    et al.
    Sullivan, Kate
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Swerdlow, Anthony
    Houlston, Richard
    The Common D302H Variant of CASP8 Is Associated with Risk of Glioma2008Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, nr 4, s. 987-989Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.

  • 238. Bethke, Lara
    et al.
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Swerdlow, Anthony
    Houlston, Richard
    Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma2008Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, nr 5, s. 1195-1202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.

  • 239. Bethke, Lara
    et al.
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Swerdlow, Anthony
    Houlston, Richard
    Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma2008Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 17, nr 6, s. 800-805Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case–control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case–control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14–1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.

  • 240.
    Bhattacharjee, Samsiddhi
    et al.
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    Rajaraman, Preetha
    Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    Jacobs, Kevin B
    Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 8717 Grovemont Circle, Gaithersburg, Maryland 20877, USA.
    Wheeler, William A
    Information Management Services, Rockville, MD 20852, USA.
    Melin, Beatrice S
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hartge, Patricia
    Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    GliomaScan Consortium,
    GliomaScan Consortium investigators and affiliations are available in the Supplemental Data.
    Yeager, Meredith
    Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 8717 Grovemont Circle, Gaithersburg, Maryland 20877, USA.
    Chung, Charles C
    Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    Chanock, Stephen J
    Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    Chatterjee, Nilanjan
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits2012Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 90, nr 5, s. 821-835Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical approaches for meta-analysis or pooled analysis, however, might not be suitable for such analysis because individual variants are likely to be associated with only a subset of the traits or might demonstrate effects in different directions. We propose a method that exhaustively explores subsets of studies for the presence of true association signals that are in either the same direction or possibly opposite directions. An efficient approximation is used for rapid evaluation of p values. We present two illustrative applications, one for a meta-analysis of separate case-control studies of six distinct cancers and another for pooled analysis of a case-control study of glioma, a class of brain tumors that contains heterogeneous subtypes. Both the applications and additional simulation studies demonstrate that the proposed methods offer improved power and more interpretable results when compared to traditional methods for the analysis of heterogeneous traits. The proposed framework has applications beyond genetic association studies.

  • 241. Bijnsdorp, Irene V.
    et al.
    Hodzic, Jasmina
    Lagerweij, Tonny
    Westerman, Bart
    Krijgsman, Oscar
    Broeke, Jurjen
    Verweij, Frederik
    Nilsson, R. Jonas A.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.
    Rozendaal, Lawrence
    van Beusechem, Victor W.
    van Moorselaar, Jeroen A.
    Wurdinger, Thomas
    Geldof, Albert A.
    miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP1102016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 13, s. 16676-16687Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

  • 242. Bisschop, Charlotte N. Steins
    et al.
    van Gils, Carla H.
    Emaus, Marleen J.
    Bueno-de-Mesquita, H. Bas
    Monninkhof, Evelyn M.
    Boeing, Heiner
    Aleksandrova, Krasmira
    Jenab, Mazda
    Norat, Teresa
    Riboli, Elio
    Boutron-Rualt, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Mattiello, Amalia
    Vicente Argueeles, Marcial
    Jose Sanchez, Maria
    Jose Tormo, Maria
    Ardanaz, Eva
    Dorronsoro, Miren
    Bonet, Catalina
    Khaw, Kay-Tee
    Key, Tim
    Trichopoulou, Antonia
    Orfanos, Philippos
    Naska, Androniki
    Kaaks, Rudolph R.
    Lukanova, Annekatrin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pischon, Tobias
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Jirstrom, Karin
    Ohlsson, Bodil
    Overvad, Kim
    Berentzen, Tina Landsvig
    Halkjaer, Jytte
    Tjonneland, Anne
    Weiderpass, Elisabete
    Skeie, Guri
    Braaten, Tonje
    Siersema, Peter D.
    Freisling, Heinz
    Ferrari, Pietro
    Peeters, Petra H. M.
    May, Anne M.
    Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study2014Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, nr 1, s. 139-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change. Objective: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk. Design: This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association. Results: A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. ME at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found. Conclusions: BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women.

  • 243.
    Bitar, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    The prevalence and clinical features of SWEDD in the NYPUM study -a retrospective analysis2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 244.
    Bjerke, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik. Department of Physiotherapy, School of Health Education & Social Work, Sør-Trøndelag University College, Trondheim, Norway.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Kjell G
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Foss, Olav A
    Orthopaedic Research Centre, Trondheim University Hospital, Trondheim, Norway.
    Stensdotter, Ann-Katrin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik. Department of Physiotherapy, School of Health Education & Social Work, Sør-Trøndelag University College, Trondheim, Norway.
    Peak knee flexion angles during stair descent in TKA patients2014Inngår i: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 29, nr 4, s. 707-711Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reduced peak knee flexion during stair descent (PKSD) is demonstrated in subjects with total knee arthroplasty (TKA), but the underlying factors are not well studied. 3D gait patterns during stair descent, peak passive knee flexion (PPKF), quadriceps strength, pain, proprioception, demographics, and anthropometrics were assessed in 23 unilateral TKA-subjects ~ 19 months post-operatively, and in 23 controls. PKSD, PPKF and quadriceps strength were reduced in the TKA-side, but also in the contralateral side. A multiple regression analysis identified PPKF as the only predictor (57%) to explain the relationship with PKSD. PPKF was, however sufficient for normal PKSD. Deficits in quadriceps strength in TKA-group suggest that strength is also contributing to smaller PKSD. Increased hip adduction at PKSD may indicate both compensatory strategy and reduced hip strength.

  • 245.
    Bjerke, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Department of Physiotherapy, School of Health Education & Social Work, Sør-Trøndelag University College, Trondheim, Norway.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nilsson, Kjell G
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Stensdotter, Ann-Katrin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Department of Physiotherapy, School of Health Education & Social Work, Sør-Trøndelag University College, Trondheim, Norway.
    Gait on soft versus hard surface after total knee arthroplastyManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Asymmetric gait patterns are common following total knee arthroplasty (TKA). Gait on even and hard surface is primarily characterized by reduced peak knee flexion in the prosthetic knee, increased contralateral knee adduction angle, and decreased walking speed compared to controls. Natural conditions may however lead to different strategies. Therefore, the objective of the present study was to explore how gait patterns may differ when walking on a soft surface. Methods: 3D kinematics during gait on hard and soft surface were assessed in 23 unilateral TKA-subjects ~19 months post-operative, and in 23 controls. Results: Gait characteristics in TKA-subjects that differed from controls observed on hard surface were amplified on soft surface. Flexion in the prosthetic knee was further decreased and a tendency towards reduced flexion in the contralateral knee was observed. Knee and hip adduction were not affected by surface conditions nevertheless there was a difference between groups, in particular with regard to the prosthetic side. In addition, step width increased on soft surface in TKA-subjects. Conclusion: Gait on an even and soft surface did not amplify asymmetries in TKA-subjects, but decreased knee flexion and increased step-width, albeit with similar gait speed as the control group suggests that the soft surface provided a small but significant challenge making the TKA-subjects precautious.

  • 246.
    Bjerke, Joakim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Department of Physiotherapy, Faculty of Health and Social Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nilsson, Kjell G
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Stensdotter, Ann-Katrin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. epartment of Physiotherapy, Faculty of Health and Social Sciences, Norwegian University of Science and Technology, Trondheim, Norway .
    Walking on a compliant surface does not enhance kinematic gait asymmetries after unilateral total knee arthroplasty2016Inngår i: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 24, nr 8, s. 2606-2613Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To investigate gait asymmetries and the effect of walking on compliant surfaces in individuals with unilateral total knee arthroplasty (TKA), hypothesizing that asymmetries would increase as an effect of the compliant surface.

    METHODS: Individuals with unilateral TKA ~19 months post-operative (n = 23, median age 59 years) recruited from one orthopaedic clinic and age- and gender-matched healthy individuals without knee complaints (n = 23, median age 56 years) walked at comfortable speed on a hard surface and on a compliant surface. 3D kinematic analyses were made for knee and hip angles in sagittal and frontal planes, stance time, step length, and gait velocity.

    RESULTS: Shorter stance time (p < 0.01) and less peak knee flexion (p < 0.001) at weight bearing acceptance was found in the prosthetic side compared with the contralateral side. Larger knee (p < 0.01) and hip (p < 0.001) adduction was found compared with healthy controls. Neither asymmetries between the prosthetic and the contralateral side nor differences compared with healthy controls were enhanced when walking on compliant surfaces compared with hard surfaces.

    CONCLUSION: The TKA group adapted their gait to compliant surfaces similarly to healthy controls. Gait asymmetries in the TKA group observed on hard surface were not enhanced, and adduction in hip and knee joints did not increase further as an effect of walking on compliant surfaces. Thus, unfavourable knee joint loading did not increase when walking on a compliant surface. This implies that recommendations for walking on soft surfaces to reduce knee joint loading are not counteracted by increased gait asymmetries and unfavourable joint loading configurations.

    LEVEL OF EVIDENCE: III.

  • 247. Bjerkvig, Rolf
    et al.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. NorLux Neuro-Oncology Laboratory, Centre de Recherche Public Santé, 84, Val Fleuri, L-1526 Luxembourg.
    Miletic, Hrvoje
    Niclou, Simone P
    Cancer stem cells and angiogenesis2009Inngår i: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 19, nr 5, s. 279-284Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Most cancers contain tumor cells that display stem cell-like characteristics. How and when such cells appear in tumors are not clear, but may involve both stochastic as well as hierarchical events Most. likely, tumor cells that display stem cell-like characteristics can undergo asymmetric cell division giving rise to tumor cells that trigger angiogenic programs. As normal stem cells the cancer stem-like cells seem to adapt to hypoxic environments and will use metabolic pathways that involve increased conversion of glucose to pyruvate and lactate, and a concomitant decrease in mitochondrial metabolism and mitochondrial mass. The molecular pathways responsible for inducing glycolysis are now being explored. These pathways seem to mediate multiple metabolic functions in cancer stem-like cells, leading to a highly migratory and angiogenesis-independent phenotype. Future challenges will be to identify and validate molecular targets involved in anaerobic metabolic pathways active in cancer stem-like cells and to determine how these pathways differ from regulatory pathways involved in normal stem cell function.

  • 248. Bjurberg, Maria
    et al.
    Kjellén, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Department of Oncology, Lund University Hospital.
    Ohlsson, Tomas
    Bendahl, Pär-Ola
    Brun, Eva
    Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer2009Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 19, nr 9, s. 1600-1605Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.

    Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.

    Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.

    Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.

  • 249.
    Björ, Bodil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Burström, Lage
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nathanaelsson, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Damber, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nilsson, Tohr
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fifty-year-follow-up of mortality among a cohort of iron-ore miners in Sweden, with specific reference to myocardial infarction mortality2009Inngår i: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 66, nr 4, s. 264-268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: This study investigates both general mortality and mortality from myocardial infarction among men employed in iron-ore mines in Sweden.

    Methods: The mortality of employees (surface and underground workers) at the iron-ore mines in Malmberget and Kiruna, Sweden was investigated. The study cohort comprised men who had been employed for at least 1 year between 1923 and 1996. The causes of death were obtained from the national cause of death register from 1952 to 2001. Indirect standardised mortality ratios (SMR) were calculated for four main causes. Mortality specifically from myocardial infarction was also analysed.

    Results: 4504 deaths in the cohort gave an SMR for total mortality of 1.05 (95% CI 1.02 to 1.09). Mortality was significantly higher for lung cancer (SMR 1.73, 95% CI 1.52 to 1.97). There was an increased risk of injuries and poisonings (SMR 1.34, 95% CI 1.24 to 1.46) and respiratory diseases (SMR 1.14, 95% CI 1.00 to 1.28). There were 1477 cases of myocardial infarction, resulting in an SMR of 1.12 (95% CI 1.07 to 1.18). SMR was higher (1.35, 95% CI 1.22 to 1.50) for men aged ≤60 years than for those >60 years of age (1.06, 95% CI 1.00 to 1.13).

    Conclusions: Mortality from myocardial infarction was higher than expected. There was also an increased risk of death from injuries and poisonings, lung cancer and respiratory diseases, as well as higher general mortality. Our findings support the results of previous studies that there is an association between working in the mining industry and adverse health outcomes.

  • 250.
    Björ, Bodil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Burström, Lage
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Karlsson, Marcus
    Nilsson, Tohr
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Acute effects on heart rate variability when exposed to hand transmitted vibration and noise.2007Inngår i: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 81, nr 2, s. 193-199Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: This study investigates possible acute effects on heart rate variability (HRV) when people are exposed to hand transmitted vibration and noise individually and simultaneously. METHODS: Ten male and 10 female subjects were recruited by advertisement. Subjects completed a questionnaire concerning their work environment, general health, medication, hearing, and physical activity level. The test started with the subject resting for 15 min while sitting down. After resting, they were exposed to one of four exposure conditions: (1) only vibration; (2) only noise; (3) both noise and vibration; or (4) a control condition of exposure to the static load only. All four exposures lasted 15 min and the resting time between the exposures was 30 min. A continuous electrocardiogram (ECG) signal was recorded and the following HRV parameters were calculated: total spectral power (P(TOT)); the spectral power of the very low frequency component (P(VLF)); the low frequency component (P(LF)); the high frequency component (P(HF)); and the ratio LF/HF. RESULTS: Exposure to only vibration resulted in a lower P(TOT) compared to static load, whereas exposure to only noise resulted in a higher P(TOT). The mean values of P(TOT), P(VLF), P(LF), and P(HF) were lowest during exposure to vibration and simultaneous exposure to vibration and noise. CONCLUSIONS: Exposure to vibration and/or noise acutely affects HRV compared to standing without these exposures. Being exposed to vibration only and being exposed to noise only seem to generate opposite effects. Compared to no exposure, P(TOT) was reduced during vibration exposure and increased during noise exposure.

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