11. |
- Rutella, S, et al.
(author)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I-conceptual challenges
- 2020
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In: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Journal article (peer-reviewed)abstract
- The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I—conceptual challenges and Volume II—practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting.
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12. |
- Sennström, Maria B., et al.
(author)
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Human cervical ripening, an inflammatory process mediated by cytokines
- 2000
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In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:4, s. 81-375
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Journal article (peer-reviewed)abstract
- An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.
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13. |
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14. |
- Arvidsson, Daniel, 1974, et al.
(author)
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A Longitudinal Analysis of the Relationships of Physical Activity and Body Fat With Nerve Growth Factor and Brain-Derived Neural Factor in Children
- 2018
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In: Journal of Physical Activity & Health. - : Human Kinetics. - 1543-3080 .- 1543-5474. ; 15:8, s. 620-625
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Journal article (peer-reviewed)abstract
- Background: Nerve growth factor (NGF) and brain-derived neural factor (BDNF) are important for brain function and detectable in the blood. This study explored the longitudinal associations of physical activity and body fat with serum NGF and BDNF in children. Methods: Two waves of measurements were performed 2 years apart in 8- to 11-year-old children, including physical activity using the ActiGraph model 7164, body composition by dual-energy X-ray absorptiometry, and serum NGF and BDNF determined by multiplex immunoassay. The first wave included 248 children. Full information maximum likelihood estimation with robust standard errors was applied in structural equation modeling. Results: Vigorous physical activity showed a direct positive longitudinal relationship with NGF (standardized coefficient beta = 0.30, P = .01) but not with BDNF (beta = 0.04, P = .84). At the same time, body fat percentage was positively related to both NGF (beta = 0.59, P < .001) and BDNF (beta = 0.17, P = .04). There was an indication of an indirect relationship of vigorous physical activity with NGF (product of unstandardized coefficient beta = -0.18, P = .02) and BDNF (beta = -0.07, P = .05) through the negative relationship with body fat percentage (beta = -0.36, P < .001). Conclusions: Vigorous physical activity is directly related to serum NGF and indirectly through the level of body fat. The relationships with serum BDNF are more complex.
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15. |
- Bjornsdottir, Gudlaug, et al.
(author)
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Longitudinal changes in size and composition of carotid artery plaques using ultrasound: Adaptation and validation of methods (inter-and intraobserver variability)
- 2014
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In: Journal for Vascular Ultrasound. - : SAGE Publications. - 1544-3175 .- 1544-3167. ; 38:4, s. 198-208
-
Journal article (peer-reviewed)abstract
- Introduction.—B-mode ultrasonography of the carotid arteries enables quantitative measurements of atherosclerotic plaque area and composition assessed as grayscale median (GSM). The purpose of this study was to set up a standardized ultrasound protocol to measure longitudinal changes in plaque area and composition and to determine the intra-and interobserver variability of the measurements in a longitudinal population based study, the Age Gene/ Environment Susceptibility Reykjavik study. Method.—A total of 219 participants from the Age Gene/Environment Susceptibility Reykjavik study (76 ± 6 years old, 36% males) underwent 2-dimensional, B-mode ultrasound examination of the carotid arteries approximately 5 years apart for a longitudinal assessment of plaque area and composition. Standardized protocol was used to acquire comparable images from both visits. Ultrasound was performed bilaterally on the common carotid artery, internal carotid artery, and bifurcation. An image analysis program was modified and adapted for a longitudinal assessment of plaque area and plaque composition by GSM. Twenty-five subjects were selected from the group of 219 for intra-and interobserver variability assessment. Results.—Intraobserver variability for plaque area ranged from 12.10 to 18.63% and 0.89 to 0.96 for coefficient of variation and correlation (r), respectively, for plaque GSM ranged from 7.77 to 8.04% and 0.86 to 0.90. Interobserver variability for plaque area was 23.29% and 0.81 and 8.55% and 0.87 for plaque GSM. Conclusion.—The results from this study show that ultrasound can be used consistently for assessment of changes in plaque area and GSM over time. This can be achieved by proper training of ultrasound sonographers and by applying and following strict image acquisition and image analysis protocols.
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16. |
- Dencker, Magnus, et al.
(author)
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Aerobic capacity related to cardiac size in young children.
- 2013
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In: Journal of Sports Medicine and Physical Fitness. - 0022-4707. ; 53:1, s. 42-47
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Journal article (peer-reviewed)abstract
- Aim:Aerobic capacity, defined as peak oxygen uptake (VO2PEAK), is generally considered to be the best single marker for aerobic fitness. We assessed if VO2PEAK is related to different cardiac dimensions in healthy young children on a population base. Methods: In a cross-sectional study, 245 children (137 boys and 108 girls) aged 8-11 years, were recruited from a population based cohort. VO2PEAK (ml/min-1/kg-1) was assessed by indirect calorimetry during a maximal exercise test. DXA-scan was used to measure lean body mass (LBM) and total fat mass (TBF). Echocardiography, with 2-dimensional guided M-mode, was performed in accordance with current guidelines. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured, and left ventricular mass (LVM) was calculated. Results: Univariate correlations were found between VO2PEAK versus LVDD r=0.44 and LA r=0.27 (both P<0.05) and LVM r=-0.06 (NS) in boys. Corresponding values for girls were; 0.55, 0.34 (both P<0.05) and 0.11 (NS). Multiple regression analysis with VO2PEAK as dependent variable and inclusion of LBM, TBF, sex, age, Tanner stage, and maximal heart rate as independent variables showed that 67% of the total variance of VO2PEAK could be explained by these variables. Including LVDD or LA in the model, added 1% additional explained variance. Conclusion: Findings from this population based cohort of young healthy children show that multiple cardiac dimensions at rest are related to VO2PEAK. However, the different cardiac dimensions contributed very little to the added explained variance of VO2PEAK.
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17. |
- Dencker, Magnus, et al.
(author)
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Aerobic fitness related to cardiovascular risk factors in young children.
- 2012
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In: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 171:4, s. 705-710
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Journal article (peer-reviewed)abstract
- Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual - mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO(2PEAK) and composite risk factor score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO(2PEAK) (P < 0.001); thus, higher VO(2PEAK) was associated with lower composite risk factor score for CVD. In conclusion, low VO(2PEAK) is associated with an elevated composite risk factor score for CVD in both young boys and girls.
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18. |
- Dencker, Magnus, et al.
(author)
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BMI and objectively measured body fat and body fat distribution in prepubertal children.
- 2007
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In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:1, s. 12-16
-
Journal article (peer-reviewed)abstract
- Background Body Mass Index (BMI) is often used as a surrogate estimate of body fat in epidemiological studies. This study explores the association between BMI, body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry (DXA) in younger children. Methods Cross-sectional study of 246 children (138 boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass (AFM), total body fat (TBF) and also total body fat as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Results We found close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r = 0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively (P < 0.05 for all r-values). However, significantly lower correlation (P < 0.001 for difference between the r-values) existed for body fat distribution (r = 0.64 for boys and 0.73 for girls). Conclusion Percentage body fat, TBF and AFM were all closely associated with BMI, suggesting that BMI serves as a good surrogate marker for obesity in population studies. However, a significantly lower correlation existed for BMI vs. body fat distribution, which may be a limitation when BMI is used to study cardiovascular risk factors in epidemiological studies.
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19. |
- Dencker, Magnus, et al.
(author)
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Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children.
- 2012
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In: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 20, s. 1104-1108
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Journal article (peer-reviewed)abstract
- In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.
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20. |
- Dencker, Magnus, et al.
(author)
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Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in pre-pubertal children.
- 2012
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In: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:8
-
Journal article (peer-reviewed)abstract
- Aim We analysed whether total body fat, abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods Cross-sectional study of 238 children aged 8-11 years. Total body fat (TBF) and abdominal fat mass (AFM) were measured by DXA. TBF was expressed as a percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO(2PEAK) ), systolic and diastolic blood pressure (SBP, DBP), and resting heart rate (RHR) were measured. Mean artery pressure (MAP) and pulse pressure (PP) were calculated. Left atrial diameter (LA) was measured, and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z-scores were calculated. Sum of z-scores for SBP, DBP, MAP, PP, RHR, LVM, LA, RWT, and -VO(2PEAK) were calculated in boys and girls, separately, and used as composite risk factor score. Results Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r=0.56, r=0.59, and r=0.48, all P<0.001, and for girls r=0.45, r=0.50, and r=0.48, all P<0.001. Conclusion Total body fat, abdominal fat and body fat distribution were all associated with higher composite risk factor scores for CVD in young children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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