| 1. |
- Kaaks, Rudolf, et al.
(author)
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Lag Times between Lymphoproliferative Disorder and Clinical Diagnosis of Chronic Lymphocytic Leukemia : A Prospective Analysis Using Plasma Soluble CD23
- 2015
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:3, s. 538-545
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Journal article (peer-reviewed)abstract
- Background: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. Methods: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. Results: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65-0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at > 45% sensitivity. Conclusions: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL. Impact: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. (c) 2014 AACR.
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| 2. |
- Andersson, Camilla, et al.
(author)
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Assessment of Whether Patients' Knowledge, Satisfaction, and Experience Regarding Their 18F-Fluoride PET/CT Examination Affects Image Quality
- 2016
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In: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 44:1, s. 21-25
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate patients’ previous knowledge, satisfaction and experience regarding a (18F)-fluoride positron emission tomography / computed tomography examination ((18F)-fluoride PET/CT) and to explore whether experienced discomfort during the examination or pain was associated with reduced image quality. A further aim was to explore whether patients’ health-related quality of life (HRQoL) was associated with their satisfaction and experiences of the examination.Methods: Fifty consecutive patients with a histopathological diagnosis of prostate cancer who were scheduled for (18F)-fluoride PET/CT were asked to participate in the study, which was performed between November 2011 and April 2013. A questionnaire was used to collect information regarding the patients’ previous knowledge and experience of the examination. Image quality assessment was performed according to an arbitrary scale. The EORTC-QLQ-C30 and QLQ-PR25 were used to assess HRQoL.Results: Forty-six patients (96%) completed the questionnaires. Twenty-six per cent of participants did not know at all what a (18F)-fluoride PET/CT examination was. The majority (52-70%) were to a very high degree satisfied with the care provided by the nursing staff but less satisfied with the information given prior to the examination. The image quality was similar in patients who were exhausted or claustrophobic during the examination and those who were not. No correlations between HRQoL and the participants’ experience of (18F)-fluoride PET/CT were found.Conclusion: The majority of participants were satisfied with the care provided by the nursing staff, but there is still room for improvement especially regarding the information prior to the examination. Long examination time may be strenuous, for the patient but there was no difference in image quality between patients who felt discomfort during the examination or pain and those who did not.
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| 3. |
- Andersson, Camilla, et al.
(author)
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Patient Experience of an 18F-FDG-PET/CT Examination: : Need for Improvements in Patient Care
- 2015
-
In: Journal of Radiology Nursing. - : Elsevier. - 1546-0843. ; 34:2, s. 100-108
-
Journal article (peer-reviewed)abstract
- The aims of this study were to investigate the patients' knowledge about and experience of an 18F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) examination and to investigate the self-reported feelings of stress, level of physical activity, and health-related quality of life (HRQoL) and to find out if this was related to how they experienced the examination. A cross-sectional survey was used to collect information on 198 patients with known or suspected malignancy. As many as 32% to 63% were satisfied with the nursing staff, the communication, and the professional skills. Most patients did not know beforehand what an FDG-PET/CT examination was. The HRQoL, level of perceived stress, and physical activity were relatively low. A better HRQoL, lower level of perceived stress, and a higher level of physical activity were correlated to a more positive experience and higher education to more knowledge about the examination (p < .01–.05). The information before the examination needs to be improved. The results may be used to improve patient care and optimize imaging procedures.
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| 4. |
- Baglietto, Laura, et al.
(author)
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DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk
- 2017
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:1, s. 50-61
-
Journal article (peer-reviewed)abstract
- DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.
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| 5. |
- Battram, Thomas, et al.
(author)
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Appraising the causal relevance of DNA methylation for risk of lung cancer
- 2019
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:5, s. 1493-1504
-
Journal article (peer-reviewed)abstract
- Background: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.Methods: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.Results: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.Conclusions: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.
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| 6. |
- Bokhorst, Stef, et al.
(author)
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Changing Arctic snow cover : A review of recent developments and assessment of future needs for observations, modelling, and impacts
- 2016
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45:5, s. 516-537
-
Research review (peer-reviewed)abstract
- Snow is a critically important and rapidly changing feature of the Arctic. However, snow-cover and snowpack conditions change through time pose challenges for measuring and prediction of snow. Plausible scenarios of how Arctic snow cover will respond to changing Arctic climate are important for impact assessments and adaptation strategies. Although much progress has been made in understanding and predicting snow-cover changes and their multiple consequences, many uncertainties remain. In this paper, we review advances in snow monitoring and modelling, and the impact of snow changes on ecosystems and society in Arctic regions. Interdisciplinary activities are required to resolve the current limitations on measuring and modelling snow characteristics through the cold season and at different spatial scales to assure human well-being, economic stability, and improve the ability to predict manage and adapt to natural hazards in the Arctic region.
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| 7. |
- Demmelmaier, Ingrid, 1960-, et al.
(author)
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Does exercise intensity matter for fatigue during (neo-)adjuvant cancer treatment? The Phys-Can randomized clinical trial
- 2021
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In: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 31:5, s. 1144-1159
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Journal article (peer-reviewed)abstract
- Exercise during cancer treatment improves cancer-related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high- vs low-to-moderate-intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo-)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo-)adjuvant treatment were randomized to high intensity (n = 144), low-to-moderate intensity (n = 144), high intensity with BCS (n = 144) or low-to-moderate intensity with BCS (n = 145). The 6-month exercise intervention included supervised resistance training and home-based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4-20), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F, score range 0-52). Multiple linear regression for main factorial effects was performed according to intention-to-treat, with post-intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high- vs low-to-moderate-intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference −1.05 [95% CI: −1.85, −0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo-)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high- or low-to-moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well-controlled exercise interventions.
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| 8. |
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| 9. |
- Fasanelli, Francesca, et al.
(author)
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Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts
- 2015
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 6
-
Journal article (peer-reviewed)abstract
- DNA hypomethylation in certain genes is associated with tobacco exposure but it is unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of DNA from pre-diagnostic blood samples from 132 case–control pairs in the NOWAC cohort, we observe that the most significant associations with lung cancer risk are for cg05575921 in AHRR (OR for 1 s.d.=0.37, 95% CI: 0.31–0.54, P-value=3.3 × 10−11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31–0.56, P-value=3.9 × 10−10), previously shown to be strongly hypomethylated in smokers. These associations remain significant after adjustment for smoking and are confirmed in additional 664 case–control pairs tightly matched for smoking from the MCCS, NSHDS and EPIC HD cohorts. The replication and mediation analyses suggest that residual confounding is unlikely to explain the observed associations and that hypomethylation of these CpG sites may mediate the effect of tobacco on lung cancer risk.
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| 10. |
- Forslund, Marina, et al.
(author)
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Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer : a multicentre randomised controlled trial.
- 2020
-
In: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 28:7, s. 3331-3342
-
Journal article (peer-reviewed)abstract
- Purpose: Radiotherapy to the prostate gland and pelvic lymph nodes may cause acute and late bowel symptoms and diminish quality of life. The aim was to study the effects of a nutrition intervention on bowel symptoms and health-related quality of life, compared with standard care.Methods: Patients were randomised to a nutrition intervention (n = 92) aiming to replace insoluble fibres with soluble and reduce intake of lactose, or a standard care group (n = 88) who were recommended to maintain their habitual diet. Bowel symptoms, health-related quality of life and intake of fibre and lactose-containing foods were assessed up to 24 months after radiotherapy completion. Multiple linear regression was used to analyse the effects of the nutrition intervention on bowel symptoms during the acute (up to 2 months post radiotherapy) and the late (7 to 24 months post radiotherapy) phase.Results: Most symptoms and functioning worsened during the acute phase, and improved during the late phase in both the intervention and standard care groups. The nutrition intervention was associated with less blood in stools (p = 0.047), flatulence (p = 0.014) and increased loss of appetite (p = 0.018) during the acute phase, and more bloated abdomen in the late phase (p = 0.029). However, these associations were clinically trivial or small.Conclusions: The effect of the nutrition intervention related to dietary fibre and lactose on bowel symptoms from pelvic RT was small and inconclusive, although some minor and transient improvements were observed. The results do not support routine nutrition intervention of this type to reduce adverse effects from pelvic radiotherapy.
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| 11. |
- Reinedahl, David, et al.
(author)
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Aseptic Ligatures Induce Marginal Peri-Implant Bone Loss-An 8-Week Trial in Rabbits
- 2019
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:8
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Journal article (peer-reviewed)abstract
- The clinical value of ligature-induced experimental peri-implantitis studies has been questioned due to the artificial nature of the model. Despite repeated claims that ligatures of silk, cotton and other materials may not induce bone resorption by themselves; a recent review showed that the tissue reaction toward them has not been investigated. Hence, the current study aimed to explore the hard and soft tissue reactions toward commonly used ligature materials. A total of 60 dental implants were inserted into the femur ( = 20) and tibia ( = 40) of 10 rabbits. The femoral implants were ligated with sterile 3-0 braided silk in one leg and sterile cotton retraction chord in the other leg. The tibial implants were ligated with silk or left as non-ligated controls. All wounds were closed in layers. After a healing time of 8 weeks, femoral (silk versus cotton) and proximal tibial (silk versus non-ligated control) implants were investigated histologically. Distal tibial (silk versus non-ligated control) implants were investigated with real time polymerase chain reaction (qPCR). The distance from the implant-top to first bone contact point was longer for silk ligated implants compared to non-ligated controls ( = 0.007), but did not vary between cotton and silk. The ligatures triggered an immunological reaction with cell infiltrates in close contact with the ligature materials, adjacent soft tissue encapsulation and bone resorption. qPCR further demonstrated an upregulated immune response toward the silk ligatures compared to non-ligated controls. Silk and cotton ligatures provoke foreign body reactions of soft tissue encapsulation type and bone resorption around implants in the absence of plaque.
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| 12. |
- Agnoletti, Davide, et al.
(author)
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Microbiota, Diet, Oral Health and Vascular Aging
- 2024. - 2
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In: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - 2nd Edition - New Directions in Cardiovascular Protection - 2nd Edition. - 9780443155123
-
Book chapter (peer-reviewed)
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| 13. |
- Almhagen, Erik, et al.
(author)
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Plan robustness and RBE influence for proton dose painting by numbers for head and neck cancers
- 2023
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In: Physica medica (Testo stampato). - : Elsevier. - 1120-1797 .- 1724-191X. ; 115, s. 103157-
-
Journal article (peer-reviewed)abstract
- PurposeTo investigate the feasibility of dose painting by numbers (DPBN) with respect to robustness for proton therapy for head and neck cancers (HNC), and to study the influence of variable RBE on the TCP and OAR dose burden.Methods and materialsData for 19 patients who have been scanned pretreatment with PET-FDG and subsequently treated with photon therapy were used in the study. A dose response model developed for photon therapy was implemented in a TPS, allowing DPBN plans to be created. Conventional homogeneous dose and DPBN plans were created for each patient, optimized with either fixed RBE = 1.1 or a variable RBE model. Robust optimization was used to create clinically acceptable plans. To estimate the maximum potential loss in TCP due to actual SUV variations from the pre-treatment imaging, we applied a test case with randomized SUV distribution.ResultsRegardless of the use of variable RBE for optimization or evaluation, a statistically significant increase (p < 0.001) in TCP was found for DPBN plans as compared to homogeneous dose plans. Randomizing the SUV distribution decreased the TCP for all plans. A correlation between TCP increase and variance of the SUV distribution and target volume was also found.ConclusionDPBN for protons and HNC is feasible and could lead to a TCP gain. Risks associated with the temporal variation of SUV distributions could be mitigated by imposing minimum doses to targets. The correlation found between TCP increase and SUV variance and target volume may be used for patient selection.
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| 14. |
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| 15. |
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| 16. |
- Bardi, Luciano, et al.
(author)
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The European Ambition : The Group of the European People’s Party and European Integration
- 2020. - 1
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Book (other academic/artistic)abstract
- This book traces the EPP Group’s institutional, organisational and political trajectory in the European Parliament, focusing on the period after the first direct elections in 1979. In doing so, it sheds light on the functioning of parliamentary party groups, while at the same time creating the conditions for a better understanding of their role in the process of European integration and in the EU’s political system.Based on the conceptual framework of different disciplines—history, political science, European studies and political sociology—this book is the outcome of a research project involving scholars with diverse academic backgrounds and from different EU countries.
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| 17. |
- Bott, Lukas Thomas, et al.
(author)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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In: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
-
Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 18. |
- Cederblad, Lena, et al.
(author)
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Cancer of the parotid gland; long-term follow-up : A single centre experience on recurrence and survival
- 2009
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:4, s. 549-555
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival. PATIENTS AND METHODS: At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume. RESULTS: The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s. CONCLUSIONS: Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.
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| 19. |
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| 20. |
- Čičić, Mladen, 1991-, et al.
(author)
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Platoon-actuated variable area mainstream traffic control for bottleneck decongestion
- 2022
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In: European Journal of Control. - : Elsevier BV. - 0947-3580 .- 1435-5671. ; 68
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Journal article (peer-reviewed)abstract
- In this paper a platoon-actuated mainstream traffic control is proposed to decongest bottlenecks due to recurrent and nonrecurrent events. Indeed, differently from traditional mainstream control strategies, i.e., control strategies applied with fixed actuators, platoon-actuated control can be applied at any location on the freeway. In this work, the control actions to be communicated to the platoons, i.e., speed and configuration, are defined by means of a predictive control law based on traffic and platoon state detected in an area identified immediately upstream of the bottleneck. The main peculiarity of this scheme is that the size of the controlled area is dynamically adjusted based on the predicted congestion at the bottleneck. This approach keeps the control law computation burden low, while not sacrificing much control performance. Specifically, the number of platoons to be controlled and the time at which the platoons begin to be controlled depend on the size of the controlled area. Simulation results reported in the paper show the effectiveness of the proposed scheme, eliminating from 60% to 80% of the delay incurred from congestion compared with the uncontrolled case, depending on the level of traffic.
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| 21. |
- Cozza, Michela, 1978-, et al.
(author)
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COVID-19 as a breakdown in the texture of social practices
- 2021
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In: Gender, Work and Organization. - : WILEY. - 0968-6673 .- 1468-0432. ; 28:S1, s. 190-208
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Journal article (peer-reviewed)abstract
- A lot of things need to be repaired and a lot of relationships are in need of a knowledgeable mending. Can we start to talk/write about them? This invitation - sent by one of the authors to the others - led us, as feminist women in academia, to join together in an experimental writing about the effects of COVID-19 on daily social practices and on potential (and innovative) ways for repairing work in different fields of social organization. By diffractively intertwining our embodied experiences of becoming together-with Others, we foreground a multiplicity of repair (care) practices COVID-19 is making visible. Echoing one another, we take a stand and say that we need to prevent the future from becoming the past. We are not going back to the past; our society has already changed and there is a need to cope with innovation and repairing practices that do not reproduce the past.
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| 22. |
- de Zwarte, Sonja M. C., et al.
(author)
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Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
- 2022
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 414-430
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Journal article (peer-reviewed)abstract
- First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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| 23. |
- Delahaye-Sourdeix, Manon, et al.
(author)
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The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract
- 2015
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In: PLOS ONE. - : Public library science. - 1932-6203. ; 10:3
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Journal article (peer-reviewed)abstract
- Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.
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| 24. |
- Edwards, Kieron D., et al.
(author)
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Circadian clock components control daily growth activities by modulating cytokinin levels and cell division-associated gene expression in Populus trees
- 2018
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In: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 41:6, s. 1468-1482
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Journal article (peer-reviewed)abstract
- Trees are carbon dioxide sinks and major producers of terrestrial biomass with distinct seasonal growth patterns. Circadian clocks enable the coordination of physiological and biochemical temporal activities, optimally regulating multiple traits including growth. To dissect the clock's role in growth, we analysed Populus tremula x P. tremuloides trees with impaired clock function due to down-regulation of central clock components. late elongated hypocotyl (lhy-10) trees, in which expression of LHY1 and LHY2 is reduced by RNAi, have a short free-running period and show disrupted temporal regulation of gene expression and reduced growth, producing 30-40% less biomass than wild-type trees. Genes important in growth regulation were expressed with an earlier phase in lhy-10, and CYCLIN D3 expression was misaligned and arrhythmic. Levels of cytokinins were lower in lhy-10 trees, which also showed a change in the time of peak expression of genes associated with cell division and growth. However, auxin levels were not altered in lhy-10 trees, and the size of the lignification zone in the stem showed a relative increase. The reduced growth rate and anatomical features of lhy-10 trees were mainly caused by misregulation of cell division, which may have resulted from impaired clock function.
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| 25. |
- Ferrari, Pietro, et al.
(author)
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Challenges in estimating the validity of dietary acrylamide measurements
- 2013
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In: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 52:5, s. 1503-1512
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Journal article (peer-reviewed)abstract
- Acrylamide is a chemical compound present in tobacco smoke and food, classified as a probable human carcinogen and a known human neurotoxin. Acrylamide is formed in foods, typically carbohydrate-rich and protein-poor plant foods, during high-temperature cooking or other thermal processing. The objectives of this study were to compare dietary estimates of acrylamide from questionnaires (DQ) and 24-h recalls (R) with levels of acrylamide adduct (AA) in haemoglobin. In the European Prospective Investigation into Cancer and Nutrition (EPIC) study, acrylamide exposure was assessed in 510 participants from 9 European countries, randomly selected and stratified by age, sex, with equal numbers of never and current smokers. After adjusting for country, alcohol intake, smoking status, number of cigarettes and energy intake, correlation coefficients between various acrylamide measurements were computed, both at the individual and at the aggregate (centre) level. Individual level correlation coefficient between DQ and R measurements (r (DQ,R)) was 0.17, while r (DQ,AA) and r (R,AA) were 0.08 and 0.06, respectively. In never smokers, r (DQ,R), r (DQ,AA) and r (R,AA) were 0.19, 0.09 and 0.02, respectively. The correlation coefficients between means of DQ, R and AA measurements at the centre level were larger (r > 0.4). These findings suggest that estimates of total acrylamide intake based on self-reported diet correlate weakly with biomarker AA Hb levels. Possible explanations are the lack of AA levels to capture dietary acrylamide due to individual differences in the absorption and metabolism of acrylamide, and/or measurement errors in acrylamide from self-reported dietary assessments, thus limiting the possibility to validate acrylamide DQ measurements.
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| 26. |
- Freisling, Heinz, et al.
(author)
-
Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region
- 2013
-
In: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 52:4, s. 1369-1380
-
Journal article (peer-reviewed)abstract
- Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In this cross-sectional analysis, 36 994 men and women, aged 35-74 years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. Adjusted mean AA intake across centers ranged from 13 to 47 mu g/day in men and from 12 to 39 mu g/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50 % of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.
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| 27. |
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| 28. |
- Garske, Ulrike, et al.
(author)
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Lessons on Tumour Response : Imaging during Therapy with Lu-177-DOTA-octreotate. A Case Report on a Patient with a Large Volume of Poorly Differentiated Neuroendocrine Carcinoma
- 2012
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In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 2:5, s. 459-471
-
Journal article (peer-reviewed)abstract
- Favourable outcomes of peptide receptor radiotherapy (PRRT) of neuroendocrine tumours have been reported during the last years. Still, there are uncertainties on the radionuclides to be used, the treatment planning, and the indication in patients with a high proliferation rate. This case report describes a patient with a high tumour burden of poorly differentiated neuroendocrine carcinoma of unknown primary with a proliferation rate in liver metastases up to 50%, undergoing fractionated treatment with 7 cycles of Lu-177-DOTA-octreotate (7.4 GBq each) after disease progression on two different chemotherapy regiments. Based on initial staging scintigraphy, somatostatin receptor expression was very high. Longitudinal dosimetry studies during therapy indicated ongoing increases in tumour-to-organ ratios that coincided with an objective response. We conclude that fractionated therapy with Lu-177-DOTA-octreotate should be considered a treatment option also for those patients with large tumours, high proliferation, and high receptor expression.
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| 29. |
- Garske, Ulrike, et al.
(author)
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Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy
- 2011
-
In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 86-96
-
Journal article (peer-reviewed)abstract
- Fractionated (177)Lu-DOTA-octreotate therapy has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. In our clinic, full individual dosimetry is performed during the first therapy cycle, while dosimetry at later cycles is based on the 24 h uptake measurement assuming an unchanged effective half-life. Our aim was to evaluate this assumption and the variation in the 24 h uptake during therapy. Patients. Thirty patients, 13 women and 17 men, were included in the study. Methods. During the first therapy cycle the (177)Lu-concentration was measured with SPECT/CT over the abdomen at 24 h, 96 h and 168 h after infusion. The effective half-life was determined for the kidneys, liver and spleen. The procedure was repeated at cycle 4 or 5. Results. The median ratio between the effective half-lives of the latter and the first cycle was 0.97 and 1.01 for the right and left kidney, with a range of 0.89-1.01 (1st-3rd quartile) and 0.93-1.05, respectively. Discussion. The mean value of the ratios was slightly lower than one, indicating a tendency towards increased activity elimination during therapy. In individual patients, significant changes were found for all organs, often when a large tumor burden reduction occurred during treatment. Possible contributing factors appeared to be larger amounts of non-tumor bound tracer, improved organ function (kidneys), decrease of vessel obstruction (spleen), less scatter from large tumors and reduction of small metastases (liver and spleen). Conclusion. With most patients it is safe to estimate absorbed doses to kidneys, liver and spleen from 24 h activity concentration assuming an unchanged effective half-life during therapy. Patients with risk factors for kidney dysfunction need to be monitored in more detail. Simplified dosimetry based on the assumption of unchanged effective half-life can function as guidance to the number of therapy cycles an individual patient can tolerate.
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| 30. |
- Garske, Ulrike, 1963-, et al.
(author)
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Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs) : feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity
- 2018
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:6, s. 970-988
-
Journal article (peer-reviewed)abstract
- PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.
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| 31. |
- Gobel, K., et al.
(author)
-
Coulomb dissociation of 16O into 4He and 12C
- 2020
-
In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1668:1
-
Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(a,?)16O fusion reaction and to reach lower center-ofmass energies than measured so far. The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-To-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
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| 32. |
- Grönlund, Eric, 1987-
(author)
-
Dose painting : Can radiotherapy be improved with image driven dose-responses derived from retrospective radiotherapy data?
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- The main aim of curative radiotherapy for cancer is to prescribe and deliver doses that eradicate the tumor and spare the normal healthy tissues. Radiotherapy is commonly performed by delivering a homogeneous radiation dose to the tumor. However, concern have been raised that functional imaging methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can provide a basis for prescribing heterogeneous doses - higher doses in malignant regions of the tumor and less dose where the tumor is less malignant. This form of radiotherapy is called “dose painting” and has the aim of utilizing the radiant energy as efficiently as possible to increase the tumor control probability (TCP) and to reduce the risk for unwanted side effects of the neighboring normal tissues.In this project we have studied how dose painting prescriptions could be derived through retrospectively analyzing pre-RT image data and post-RT outcomes for two different patient groups: one diagnosed with head and neck cancer with pre-RT fluorodeoxyglucose (18F-FDG) PET image data; and one patient group diagnosed with prostate cancer with pre-RT Gleason score data that were constructed to be mapped from apparent diffusion coefficient (ADC) data acquired from MRI. The resulting dose painting prescriptions for each of these diagnoses indicated that the TCP could be increased without increasing the average dose to the tumor volumes as compared to homogeneous dose treatments. These TCP increases were more noticeable when the tumors were larger and more heterogeneous than for smaller and more homogeneous tumors.We have also studied the potential to realize TCP increases with dose painting in comparison to homogeneous dose treatments by optimizing clinically deliverable dose painting plans for both diagnoses, i.e. head and neck cancer and prostate cancer. These plans were optimized with minimax optimization that aimed to maximize a robust TCP increase by considering uncertainties of the patient geometry. These plan optimizations indicated that the TCP compared to homogeneous dose treatments was increasing and robust regarding uncertainties of the patient geometry.
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| 33. |
- Grönlund, Eric, et al.
(author)
-
Dose painting by numbers based on retrospectively determined recurrence probabilities
- 2017
-
In: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 122:2, s. 236-241
-
Journal article (peer-reviewed)abstract
- Background and purpose: The aim of this study is to derive "dose painting by numbers" prescriptions from retrospectively observed recurrence volumes in a patient group treated with conventional radiotherapy for head and neck squamous cell carcinoma. Materials and methods: The spatial relation between retrospectively observed recurrence volumes and pre-treatment standardized uptake values (SUV) from fluorodeoxyglucose positron emission tomography (FDG-PET) imaging was determined. Based on this information we derived SUV driven dose-response functions and used these to optimize ideal dose redistributions under the constraint of equal average dose to the tumor volumes as for a conventional treatment. The response functions were also implemented into a treatment planning system for realistic dose optimization. Results: The calculated tumor control probabilities (TCP) increased between 0.1-14.6% by the ideal dose redistributions for all included patients, where patients with larger and more heterogeneous tumors got greater increases than smaller and more homogeneous tumors. Conclusions: Dose painting prescriptions can be derived from retrospectively observed recurrence volumes spatial relation to pre-treatment FDG-PET image data. The ideal dose redistributions could significantly increase the TCP for patients with large tumor volumes and large spread in SUV from FDG-PET. The results yield a basis for prospective studies to determine the clinical value for dose painting of head and neck squamous cell carcinomas.
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| 34. |
- Grönlund, Eric, et al.
(author)
-
Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients
- 2018
-
In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:5, s. 574-581
-
Journal article (peer-reviewed)abstract
- Background: Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.Methods: The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.Results: The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0–51% for the learning set and by 4–30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.Conclusions: We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.
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| 35. |
- Grönlund, Eric, 1987-, et al.
(author)
-
Robust maximization of tumor control probability for radicality constrained dose painting by numbers of head and neck cancer
-
Journal article (peer-reviewed)abstract
- Background and Purpose The aim of this study was to evaluate the potential and robustness to increase the tumor control probability (TCP) for robustly optimized dose painting plans compared to conventional homogeneous dose plans for head and neck cancers.Material and Methods We optimized a set of dose painting plans with a robust TCP maximizing objective under different mean dose constraints for the primary clinical target volume (CTVT). These plans were optimized with the robust mini-max algorithm together with dose-responses driven by standardized uptake values (SUV) from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The robustness in TCP was evaluated through sampling treatment scenarios with iso-center displacements. We also analyzed the impact on TCP predictions by considering dose-response uncertainties.Results The average increase in TCP with dose painting ranged between 3 to 20 percentage points (p.p.) which depended on the allowed integral CTVT dose. The median deviation in TCP increase was below 1p.p. for all sampled treatment scenarios versus the nominal plans. Patients with large tumors and large spread of SUV gained the greatest TCP increases. By considering dose-response uncertainties, a decrease of the TCP for a homogeneous dose yielded an increasing dose painting potential.Conclusions We have found that it is feasible to optimize FDG-PET driven dose painting plans that robustly increase the TCP compared to homogeneous dose treatments for head and neck cancers. The greatest potential TCP increases were found for patients with larger and more SUV heterogeneous tumors, which may give guidance for patient selection to further test the presented dose painting formalism.
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| 36. |
- Grönlund, Eric, 1987-, et al.
(author)
-
Robust maximization of tumor control probability for radicality constrained dose painting by numbers of head and neck cancer
-
Journal article (peer-reviewed)abstract
- Background and Purpose The aim of this study was to evaluate the potential and robustness to increase the tumor control probability (TCP) for robustly optimized dose painting plans compared to conventional homogeneous dose plans for head and neck cancers.Material and Methods We optimized a set of dose painting plans with a robust TCP maximizing objective under different mean dose constraints for the primary clinical target volume (CTVT). These plans were optimized with the robust mini-max algorithm together with dose-responses driven by standardized uptake values (SUV) from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The robustness in TCP was evaluated through sampling treatment scenarios with iso-center displacements. We also analyzed the impact on TCP predictions by considering dose-response uncertainties.Results The average increase in TCP with dose painting ranged between 3 to 20 percentage points (p.p.) which depended on the allowed integral CTVT dose. The median deviation in TCP increase was below 1p.p. for all sampled treatment scenarios versus the nominal plans. Patients with large tumors and large spread of SUV gained the greatest TCP increases. By considering dose-response uncertainties, a decrease of the TCP for a homogeneous dose yielded an increasing dose painting potential.Conclusions We have found that it is feasible to optimize FDG-PET driven dose painting plans that robustly increase the TCP compared to homogeneous dose treatments for head and neck cancers. The greatest potential TCP increases were found for patients with larger and more SUV heterogeneous tumors, which may give guidance for patient selection to further test the presented dose painting formalism.
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| 37. |
- Grönlund, Eric, 1987-, et al.
(author)
-
Robust maximization of tumor control probability for radicality constrained radiotherapy dose painting by numbers of head and neck cancer
- 2019
-
In: Physics and Imaging in Radiation Oncology. - : ELSEVIER. - 2405-6316. ; 12, s. 56-62
-
Journal article (peer-reviewed)abstract
- Background and purpose: Radiotherapy with dose painting by numbers (DPBN) needs another approach than conventional margins to ensure a geometrically robust dose coverage for the tumor. This study presents a method to optimize DPBN plans that as opposed to achieve a robust dose distribution instead robustly maximize the tumor control probability (TCP) for patients diagnosed with head and neck cancer. Material and methods: Volumetric-modulated arc therapy (VMAT) plans were optimized with a robust TCP maximizing objective for different dose constraints to the primary clinical target volume (CTVT) for a set of 20 patients. These plans were optimized with minimax optimization together with dose-responses driven by standardized uptake values (SUV) from F-18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). The robustness in TCP was evaluated through sampling treatment scenarios with isocenter displacements. Results: The average increase in TCP with DPBN compared to a homogeneous dose treatment ranged between 3 and 20 percentage points (p.p.) which depended on the different dose constraints for the CTVT. The median deviation in TCP increase was below 1p.p. for all sampled treatment scenarios versus the nominal plans. The standard deviation of SUV multiplied by the CTVT volume were found to correlate with the TCP gain with R-2 >= 0.9. Conclusions: Minimax optimization of DPBN plans yield, based on the presented TCP modelling, a robust increase of the TCP compared to homogeneous dose treatments for head and neck cancers. The greatest TCP gains were found for patients with large and SUV heterogeneous tumors, which may give guidance for patient selection in prospective trials.
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| 38. |
- Grönlund, Eric, 1987-, et al.
(author)
-
Robust treatment planning of dose painting for prostate cancer based on ADC-to-Gleason score mappings : what is the potential to increase the tumor control probability?
- 2021
-
In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:2, s. 199-206
-
Journal article (peer-reviewed)abstract
- Background and Purpose The aim of this study was to evaluate the potential to increase the tumor control probability (TCP) with ‘dose painting by numbers’ (DPBN) plans optimized in a treatment planning system (TPS) compared to uniform dose plans. The DPBN optimization was based on our earlier published formalism for prostate cancer that is driven by dose-responses of Gleason scores mapped from apparent diffusion coefficients (ADC).Material and MethodsFor 17 included patients, a set of DPBN plans were optimized in a TPS by maximizing the TCP for an equal average dose to the prostate volume (CTVT) as for a conventional uniform dose treatment. For the plan optimizations we applied different photon energies, different precisions for the ADC-to-Gleason mappings, and different CTVT positioning uncertainties. The TCP increasing potential was evaluated by the DPBN efficiency, defined as the ratio of TCP increases for DPBN plans by TCP increases for ideal DPBN prescriptions (optimized without considering radiation transport phenomena, uncertainties of the CTVT positioning, and uncertainties of the ADC-to-Gleason mapping).ResultsThe median DPBN efficiency for the most conservative planning scenario optimized with a low precision ADC-to-Gleason mapping, and a positioning uncertainty of 0.6 cm was 10%, meaning that more than half of the patients had a TCP gain of at least 10% of the TCP for an ideal DPBN prescription. By increasing the precision of the ADC-to-Gleason mapping, and decreasing the positioning uncertainty the median DPBN efficiency increased by up to 40%.ConclusionsTCP increases with DPBN plans optimized in a TPS were found more likely with a high precision mapping of image data into dose-responses and a high certainty of the tumor positioning. These findings motivate further development to ensure precise mappings of image data into dose-responses and to ensure a high spatial certainty of the tumor positioning when implementing DPBN clinically.
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| 39. |
- Hederström, Veronica, et al.
(author)
-
White clover pollinators and seed set in relation to local management and landscape context
- 2024
-
In: Agriculture, Ecosystems and Environment. - 0167-8809. ; 365
-
Journal article (peer-reviewed)abstract
- Bees are declining, which is worrisome since they both have intrinsic conservation value and play a major role as pollinators in both natural and managed ecosystems. Land use change and lack of suitable habitats are often suggested as driving forces of bee decline. To propose mitigation measures to halt bee decline, it is important to understand how land use relates to bee abundance and diversity, and to explore consequences for their provision of pollination services. White clover, Trifolium repens, is an outcrossing mass-flowering crop, which could serve as an abundant, although ephemeral, food resource for bees. We investigated how the bee community in 39 fields of white clover grown for seed, related to local field management (organic, conventional without insecticides and conventional with insecticides) and landscape context (proportion semi-natural land), and how this pollinator community related to white clover seed set. The honey bee, Apis mellifera, was the most commonly observed bee species, and two generalist bumble bee species, Bombus terrestris and B. lapidarius, were the subsequently most common. We observed fewer non-Apis bees, and a lower bee species richness in organic white clover seed fields compared to conventional fields independent of insecticide treatment. Bee species richness in both conventional and organic fields were positively related to the proportion of semi-natural land in the landscape, likely because of a larger species pool in such landscapes. Initial seed set in immature inflorescences was positively related to bee abundance, whereas final seed set in mature inflorescences was unrelated to bee abundance, possibly as a consequence of seed-eating weevils consuming a large proportion of the seeds. We conclude that both bee visitation and seed set in white clover benefit from conventional management and that landscapes rich in semi-natural habitats will make future crop production more resilient. The observed positive relationship between bee abundance and initial seed set suggests that if we can mitigate pest impacts and increase bee abundance in clover seed fields, the final seed yield can be increased. Thus, bee decline should be considered and mitigated both to maintain biodiversity in general and for crop seed production specifically.
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| 40. |
- Heil, M., et al.
(author)
-
A new Time-of-flight detector for the R 3 B setup
- 2022
-
In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 58:12
-
Journal article (peer-reviewed)abstract
- We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.
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| 41. |
- Hüttner, Silvia, 1984, et al.
(author)
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Recent advances in the intellectual property landscape of filamentous fungi
- 2020
-
In: Fungal Biology and Biotechnology. - : Springer Science and Business Media LLC. - 2054-3085. ; 7:1
-
Research review (peer-reviewed)abstract
- For centuries, filamentous fungi have been used in the making of food and beverages, and for decades for the production of enzymes and pharmaceuticals. In the last decades, the intellectual property (IP) landscape for fungal technology has seen an ever increasing upward trend, introducing new and promising applications utilising fungi. In this review, we highlight fungi-related patent applications published during the last 5 years (2015–2020), identify the key players in each field, and analyse future trends. New developments in the field of fungal technology include the increased use of filamentous fungi as a food source (mycoprotein), using fungi as biodegradable materials, in wastewater treatment, in integrated biorefineries and as biological pest agents. Biotechnology companies in Europe and the US are currently leading when it comes to the number of patents in these areas, but Asian companies and research institutes, in particular in China, are becoming increasingly important players, for example in pesticide formulation and agricultural practices.
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| 42. |
- Jinno, Yohei, et al.
(author)
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Impact of salivary contamination during placement of implants with simultaneous bony augmentation in iliac bone in sheep
- 2019
-
In: British Journal of Oral & Maxillofacial Surgery. - : Elsevier. - 0266-4356 .- 1532-1940. ; 57:10, s. 1131-1136
-
Journal article (peer-reviewed)abstract
- Our aim was to investigate the possible impact of contamination with saliva on osseointegration during placement of implants with simultaneous bone augmentation. Six hemispheric shape bone defects (8mm in diameter×4mm deep) were prepared in each iliac bone of six sheep. A dental implant (2.9mm in diameter×10mm long) was placed in the centre of each defect, and then pairs of defects were filled with one of the following bone augmentation materials: autogenous bone, autogenous bone plus bovine bone, or resorbable biphasic ceramic bone substitute. One site in each augmentation group was impregnated with saliva (contaminated group), while the other was not (non-contaminated group). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads were measured after a healing period of five weeks, both in respect of the implant inserted in the augmented bone and in that inserted in the residual bone. Overall results showed that there was a significant difference between the contaminated and non-contaminated group for BIC in the augmented implant (p=0.028), while there were no significant differences in the implant in residual bone (p=0.722). For BAFO, there were no significant differences between the contaminated and non-contaminated groups among the different augmentation materials. The results showed that contamination with saliva during placement of an implant with simultaneous bone augmentation had a serious deleterious effect on osseointegration of the aspect of the implant within the augmented defect. Contamination with saliva during placement of an implant with simultaneous bone augmentation should therefore be avoided.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Johansson, Inger, 1962, et al.
(author)
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Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells.
- 2008
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:5, s. 2191-9
-
Journal article (peer-reviewed)abstract
- Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
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| 47. |
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| 48. |
- Johansson, Patrik, et al.
(author)
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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- 2020
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:2
-
Journal article (peer-reviewed)abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.
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| 49. |
- Johansson, Silvia, et al.
(author)
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High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer
- 2019
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In: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 141, s. 164-173
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Journal article (peer-reviewed)abstract
- Purpose: We report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups.Methods: Proton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications. Advanced imaging was performed for adequate staging, and at an early stage of rising PSA, to identify the relapse site. Endpoints were PSA relapse-free-, locoregional relapse-free-, and distant metastasis-free- survival. Prostate cancer-specific-, metastasis-free-, and overall survival were also estimated. Genitourinary (GU) and gastrointestinal (GI) toxicity were based on patients' questionnaires and physicians' records.Results: We treated 531 patients between 2002 and 2015; 504 had localized disease. The cohort included 180 patients with T3/T4 disease (36%). The majority of the 50% with high-/very high-risk disease received ADT, 9-24 months; 92 had adjuvant pelvic node treatment. Median follow-up was 113 months (43-193). For low-, intermediate-, high-, and very high-risk patients, the 5-year PSA relapse-free survival was 100%, 94%, 82%, and 72%, respectively. Prolonged ADT improved biochemical control and nodal treatment regional control. The NCCN classification had higher predictive discrimination than the ISUP classification. The 5-year prevalence grade 3+ was 2% for GU and 0% for GI toxicity in pre-treatment symptom-free patients, and not worsened by nodal treatment.Conclusion: Dose escalation with hypofractionated proton boost was as effective as reported with high dose-rate brachytherapy boost, and the GU and GI toxicity profile was very similar. The proton boost was also appropriate for patients with larger prostate volume, higher T-stage, and high-risk disease encompassing elective regional node photon therapy.
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- Johansson, Silvia, et al.
(author)
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Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer
- 2012
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In: Prostate Cancer. - : Hindawi Limited. - 2090-3111 .- 2090-312X. ; 2012
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Journal article (peer-reviewed)abstract
- Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.
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