| 1. |
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| 2. |
- Middeldorp, Christel M., et al.
(author)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Journal article (peer-reviewed)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Muysoms, F. E., et al.
(author)
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European Hernia Society guidelines on the closure of abdominal wall incisions
- 2015
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In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 19:1, s. 1-24
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Research review (peer-reviewed)abstract
- Background The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. Methods The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. Results For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. Recommendations To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.
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| 4. |
- Nordvall-Lassen, M., et al.
(author)
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Leisure time physical activity in 9- to 11-year-old children born moderately preterm : A cohort study
- 2018
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Physical activity is one of the best documented activities with impacts on health in children and adults. Children born preterm show reduced physical and psychosocial function compared to children born at term. This may influence their level of physical activity. Reports on moderately preterm children's physical activities during childhood are limited. Thus, the aim of this study was to compare the leisure time physical activity at age 9-11years of moderately preterm children with that of children born at term. Methods: Data from 4941 mother-child pairs from the Aarhus Birth Cohort (1989-91) were used. The cohort gathered clinical information, including gestational age at delivery. Information about parental socio-demographic and lifestyle factors was obtained from questionnaires completed during the second trimester of pregnancy. Information about children's physical activities was reported in a 9- to 11-year follow-up questionnaire completed by parents detailing how many times per week their child participated in sports activities outside of school, hours spent per week playing outside, and hours per week engaged in sedentary activities. Data were analysed using multiple logistic regression with the lowest activity group as a reference group. Results: A total of 158 children (3.2%) were born moderately preterm, i.e., between 32 and 36 completed weeks. Children born moderately preterm participated in sports activities as often as their peers born at term; they also participated in frequent sports activities (≥ 4 times per week) as often as their peers. There were no differences in hours per week spent playing outside or in sedentary activities between the two groups. Conclusions: Nine- to 11-year-old moderately preterm children participated in sports activities outside school to a similar extent as their peers and engaged in outdoor activities and sedentary activities for the same duration of time per week as their peers born at term.
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| 5. |
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| 6. |
- Grand, J., et al.
(author)
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Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest
- 2019
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In: Biomarkers. - 1354-750X. ; 24:6, s. 584-591
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Journal article (peer-reviewed)abstract
- Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1–quartile 3) tau-A (ng/ml) values were 58 (43–71) versus 51 (43–67), 72 (57–84) versus 71 (59–82) and 76 (61–92) versus 75 (64–89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29–50) versus 36 (29–49), 49 (38–58) versus 48 (33–59) and 48 (39–59) versus 48 (36–62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
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| 7. |
- Haldrup, Kristoffer, et al.
(author)
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Ultrafast X-Ray Scattering Measurements of Coherent Structural Dynamics on the Ground-State Potential Energy Surface of a Diplatinum Molecule
- 2019
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In: Physical Review Letters. - 0031-9007. ; 122:6
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Journal article (peer-reviewed)abstract
- We report x-ray free electron laser experiments addressing ground-state structural dynamics of the diplatinum anion Pt2POP4 following photoexcitation. The structural dynamics are tracked with <100 fs time resolution by x-ray scattering, utilizing the anisotropic component to suppress contributions from the bulk solvent. The x-ray data exhibit a strong oscillatory component with period 0.28 ps and decay time 2.2 ps, and structural analysis of the difference signal directly shows this as arising from ground-state dynamics along the PtPt coordinate. These results are compared with multiscale Born-Oppenheimer molecular dynamics simulations and demonstrate how off-resonance excitation can be used to prepare a vibrationally cold excited-state population complemented by a structure-dependent depletion of the ground-state population which subsequently evolves in time, allowing direct tracking of ground-state structural dynamics.
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| 8. |
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| 9. |
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| 10. |
- Rizos, A., et al.
(author)
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A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short- and long-acting dopamine agonists
- 2016
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In: European Journal of Neurology. - : Wiley. - 1351-5101. ; 23:8, s. 1255-1261
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Journal article (peer-reviewed)abstract
- Background and purpose: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short- or long-acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care. Methods: A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short- and long-acting, and transdermal) across a broad range of disease stages and age groups was performed. Results: Four hundred and twenty-five cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; P <0.05) compared with any other assessed DAs except for prolonged release PPX (PPX-PR). The rate of ICDs for PPX-PR (6.6%) was significantly lower than for immediate release PPX (PPX-IR) (19.0%; P <0.05). Discontinuation rates of DA therapy due to ICDs were low. Conclusion: Our data suggest a relatively low rate of ICDs with long-acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.
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| 11. |
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| 12. |
- Stage, Tore B., et al.
(author)
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Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists : a self-controlled register study
- 2016
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:1, s. 129-133
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Journal article (peer-reviewed)abstract
- Background: It is not known whether initiation of antidiabetic treatment affects the effect of vitamin K antagonists (VKAs). It was previously shown that metformin affects the effect of one VKA, phenprocoumon. Objectives: The aim of this study was to determine if initiation of glucose-lowering treatment affects the international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. Patients/methods: We performed a self-controlled retrospective register-based study. A total of 118 patients commencing glucose-lowering treatment while being treated with warfarin or phenprocoumon were included in the study. We compared INR, dose/INR and proportion of patients with at least one sub-therapeutic INR measurement before and after initiation of glucose-lowering treatment. Results: Initiation of glucose-lowering treatment caused mean INR to decrease from 2.5 to 2.2 (decrease of -0.3 [95% CI: -0.1; -0.5]) and led to more than half of the patients having at least one sub-therapeutic INR measurement. Six to 12 weeks later, the VKA dose/INR was increased by 11%, indicating a weakened effect of the VKA. Conclusion: Initiation of glucose-lowering treatment reduces the anticoagulant effect of VKAs to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation.
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| 13. |
- Biasin, Elisa, et al.
(author)
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Anisotropy enhanced X-ray scattering from solvated transition metal complexes
- 2018
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In: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 306-315
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Journal article (peer-reviewed)abstract
- Time-resolved X-ray scattering patterns from photoexcited molecules in solution are in many cases anisotropic at the ultrafast time scales accessible at X-ray free-electron lasers (XFELs). This anisotropy arises from the interaction of a linearly polarized UV-Vis pump laser pulse with the sample, which induces anisotropic structural changes that can be captured by femtosecond X-ray pulses. In this work, a method for quantitative analysis of the anisotropic scattering signal arising from an ensemble of molecules is described, and it is demonstrated how its use can enhance the structural sensitivity of the time-resolved X-ray scattering experiment. This method is applied on time-resolved X-ray scattering patterns measured upon photoexcitation of a solvated di-platinum complex at an XFEL, and the key parameters involved are explored. It is shown that a combined analysis of the anisotropic and isotropic difference scattering signals in this experiment allows a more precise determination of the main photoinduced structural change in the solute, i.e. the change in Pt - Pt bond length, and yields more information on the excitation channels than the analysis of the isotropic scattering only. Finally, it is discussed how the anisotropic transient response of the solvent can enable the determination of key experimental parameters such as the instrument response function.The analysis of time-resolved X-ray scattering patterns collected at an XFEL upon photoexcitation of a di-platinum complex in solution is described. The analysis quantitatively considers the anisotropy of the signal.
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| 14. |
- Christensen, Robin, et al.
(author)
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Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1
- 2015
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In: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 67:5, s. 640-650
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Journal article (peer-reviewed)abstract
- Objective. To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). Methods. We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results. Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion. A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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| 15. |
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| 16. |
- Hattinger, Monika, 1969-, et al.
(author)
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Management Strategies For Knowledge Transformation : A Study Of Learning Effects In Industry-Union-University Collaborative E-Learning Initiatives
- 2018
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In: ICERI2018 Proceedings. - : International Association for Technology, Education and Development. - 9788409059485 ; , s. 10049-10057
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Conference paper (peer-reviewed)abstract
- Competence development on academic level is a key factor for industries in times of increased digitalization of manufacturing work. To develop competitive manufacturing requires employees with expert knowledge. Even if individual employees’ motivation for learning is essential, management need to put efforts on competence development and encourage education that, combine theory and practice in forms of work-integrated learning. Blended e-learning courses on university level has been successful for supporting such competence development needs, which here is described as work-integrated e-learning, e-WIL. In this study, we explore practitioners’ knowledge transformation after their participation in blended e-WIL courses that are designed with industry target content aiming for workplace transformation. Specifically, we focus on the learning efforts versus the management strategies after e-learning initiatives that have an effect on workplace transformations. The industry target courses are designed in collaboration between an industry-union-university venture of a Norwegian industry network, the Addisco union and a Swedish university. Six courses are included comprising three course subjects; Logistics and Supply Chain Management, Engineering Tools, and Robotics and Automation. Addisco was the facilitator for engaging industry-university collaboration, and stimulated co-creation between industry companies. Data was collected through a longitudinal action research project, comprising six focus group sessions with 113 industry participants during 2015 and 2018. We analysed the company management support of knowledge transformation through the course participants’ experiences after the course interventions. Overall results show that most participants experience a low management support of knowledge transformation as an engine for workplace transformation, after conducting e-WIL courses. Stimulation of individual motivation and new skills gained were not promoted within the workplace structures. There seem to be a lack of individual competence plans, time for studies, business models and routines, networking and recognition of the individuals’ knowledge transformation. Rather, participants claimed individual responsibilities, and motivation that drives them to competence development. We therefore argue for stronger management awareness and to develop company strategies that fully appreciate the added values and new knowledge that industry participants bring back after course participation.
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| 17. |
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| 18. |
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| 19. |
- Henriksen, M. W., et al.
(author)
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De novo mutations in SCN1A are associated with classic Rett syndrome: a case report
- 2018
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In: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 19
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Journal article (peer-reviewed)abstract
- Background: Rett syndrome (RTT) is a neurodevelopmental disorder. In more than 95% of females with classic RTT a pathogenic mutation in MECP2 has been identified. This leaves a small fraction of classic cases with other genetic causes. So far, there has not been reported any other gene that may account for the majority of these cases. Case presentation: We describe two females who fulfill the diagnostic criteria for classic RTT, with pathogenic de novo mutations in SCN1A, which usually leads to Dravet syndrome. The developmental history and clinical features of these two females fits well with RTT, but they do have an unusual epileptic profile with early onset of seizures. Investigation of mRNA from one of the females showed a significantly reduced level of MECP2 mRNA. Conclusions: To our knowledge, this is the first report suggesting that SCN1A mutations could account for a proportion of the females with classic RTT without MECP2 mutations. As a consequence of these findings SCN1A should be considered in the molecular routine screening in MECP2-negative individuals with RTT and early onset epilepsy.
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| 20. |
- Henriksen, M. W., et al.
(author)
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Epilepsy in classic Rett syndrome: Course and characteristics in adult age
- 2018
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In: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 145, s. 134-139
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Journal article (peer-reviewed)abstract
- Purpose: Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females. Epilepsy is a major clinical feature, but its long-term course in RTT has not been sufficiently explored. This study addresses the development of the epilepsy in adults with KIT. Methods: Available females diagnosed with RTT in Norway were asked to participate. Parents/caregivers were interviewed, the girls/women were examined and their medical records reviewed. Participants were categorized according to age, epilepsy, seizure patterns and mutation severity groups. RTT severity was assessed (epilepsy score excluded). Results: 70 females with classic RTT were included. A presumed pathogenic mutation in MECP2 was found in 96%. The presence of active epilepsy (seizures last five years) was similar in all age groups above the age of ten: 11 (65%) in adolescents (11-20 years), 9 (60%) in young adults (21-30 years) and 14 (67%) in participants above 30 years of age. Tonic-clonic seizures within the last year were present in 55, 67 and 64%, and >= weekly seizures occurred in 27, 45 and 50% in the respective age groups. Among participants with active epilepsy, 69% had unremitting seizures, whereas 31% had experienced remissions for more than six months during the last five years. In the oldest group ( > 30 years), only 19% had obtained seizure control for > 5 years, and 14% had never experienced seizures. Seizure activity correlated with RTT severity score, whereas the relationship to mutation type remained ambiguous. Conclusion: Epilepsy continues to be a major concern in adults with RTT. Two thirds of women above 30 years of age remained with active epilepsy and 50% of them had seizures at least weekly.
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| 21. |
- Henriksen, T. I., et al.
(author)
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Dysregulated autophagy in muscle precursor cells from humans with type 2 diabetes
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Autophagy is active during cellular remodeling including muscle differentiation. Muscle differentiation is dysregulated in type 2 diabetes and we therefore hypothesize that muscle precursor cells from people with type 2 diabetes (T2DM) have a dysregulation of their autophagy leading to impaired myogenesis. Muscle precursor cells were isolated from people with T2DM or healthy controls and differentiated in vitro. Autophagy marker levels were assessed by immunoblotting. Differentially expressed autophagy-related genes between healthy and T2DM groups were identified based on a previously published RNA-sequencing data-set, which we verified by RT-qPCR. siRNA was used to assess the function of differentially expressed autophagy genes. Basal autophagy increases during human muscle differentiation, while T2DM muscle cells have reduced levels of autophagy marker ATG7 and show a blunted response to starvation. Moreover, we demonstrate that the 3 non-canonical autophagy genes DRAM1, VAMP8 and TP53INP1 as differentially expressed between healthy and T2DM groups during myoblast differentiation, and that T53INP1 knock-down alters expression of both pro-and anti-apoptotic genes. In vitro differentiated T2DM muscle cells show differential expression of autophagy-related genes. These genes do not regulate myogenic transcription factors but may rather be involved in p53-associated myoblast apoptosis during early myogenesis.
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| 22. |
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| 23. |
- Højfeldt, Sofie G., et al.
(author)
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Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008
- 2019
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:3, s. 405-417
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Journal article (peer-reviewed)abstract
- Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.
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| 24. |
- Katri, A., et al.
(author)
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A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
- 2019
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In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:9, s. 1339-1346
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Journal article (peer-reviewed)abstract
- Objectives: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Methods: Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs in vitro antiresorptive effects were assessed using human osteoclasts cultured on bone. Results: The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption in vitro. Conclusions: Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.
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| 25. |
- O'Bryant, Sid E, et al.
(author)
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Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.
- 2016
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:1, s. 45-58
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Journal article (peer-reviewed)abstract
- The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.
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| 26. |
- O'Bryant, Sid E, et al.
(author)
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Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.
- 2015
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 11:5, s. 549-560
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Journal article (peer-reviewed)abstract
- The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.
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| 27. |
- Odin, Per, et al.
(author)
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Viewpoint and practical recommendations from a movement disorder specialist panel on objective measurement in the clinical management of Parkinson's disease
- 2018
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In: Npj Parkinson's Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 4
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Journal article (peer-reviewed)abstract
- Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life). Defining cutoffs by consensus, which can be subsequently tested and refined, is the first step to optimizing OM in the management of PD. OM should be used by all clinicians that treat people with PD but the least experienced may find the most value, but this requires guidance from experts to allow non-experts to apply guidelines. While evidence is gained for devices that produce OM, expert opinion is needed to supplement the evidence base.
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| 28. |
- Oskarsson, T., et al.
(author)
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Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
- 2018
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In: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
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Journal article (other academic/artistic)abstract
- Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk.Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks.Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively.Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone strength and prevent fractures should be encouraged.
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| 30. |
- Sahlstrom, T., et al.
(author)
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Workforce participation and activities in Parkinson's disease patients receiving device-aided therapy
- 2018
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 138:1, s. 78-84
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Journal article (peer-reviewed)abstract
- Objectives: Many countries have an aging population, and it is thus likely that Parkinson's disease (PD) will become an increasing health problem. It is important to ensure this group can use their resources in the best way possible, including remaining in the work market. This study aimed to investigate workforce participation and daily activities among patients with PD receiving device-aided therapy to provide new knowledge that may be used to inform decisions about these therapy options.Materials and Methods:This was a retrospective, descriptive quantitative pilot study, including 67 patients with PD from 3 centers in Sweden and Denmark. Included patients were younger than 67years at the time of introduction of device-aided therapy. Eligible patients were identified by the Swedish national Parkinson patient registry or by the treating neurologist. Quantitative interviews were made by telephone.Results:A majority of the patients could perform the same, or more, amount of activities approximately 5years after the introduction of device-aided therapy. A small number of patients receiving deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG) were able to increase their work capacity within 1year of initiating device-aided therapy and a remarkably high share could still work at the end-point of this study, approximately 15years since the diagnosis of PD.Conclusions:Device-aided therapy may sustain or increase daily activities and workforce participation in patients with PD who have not yet reached retirement age. There is need for prospective studies, both quantitative and qualitative, to confirm these results.
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| 31. |
- Svendsen, John Inge, et al.
(author)
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Glacial and environmental changes over the last 60000years in the Polar Ural Mountains, Arctic Russia, inferred from a high-resolution lake record and other observations from adjacent areas
- 2019
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In: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 48:2, s. 407-431
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Journal article (peer-reviewed)abstract
- Our knowledge about the glaciation history in the Russian Arctic has to a large extent been based on geomorphological mapping supplemented by studies of short stratigraphical sequences found in exposed sections. Here we present new geochronological data from the Polar Ural Mountains along with a high-resolution sediment record from Bolshoye Shchuchye, the largest and deepest lake in the mountain range. Seismic profiles show that the lake contains a 160-m-thick sequence of unconsolidated lacustrine sediments. A well-dated 24-m-long core from the southern end of the lake spans the last 24cal. ka. From downward extrapolation of sedimentation rates we estimate that sedimentation started about 50-60 ka ago, most likely just after a large glacier had eroded older sediments from the basin. Terrestrial cosmogenic nuclide (TCN) exposure dating (Be-10) of boulders and Optically Stimulated Luminescence (OSL) dating of sediments indicate that this part of the Ural Mountains was last covered by a coherent ice-field complex during Marine Isotope Stage (MIS) 4. A regrowth of the glaciers took place during a late stage of MIS 3, but the central valleys remained ice free until the present. The presence of small- and medium-sized glaciers during MIS 2 is reflected by a sequence of glacial varves and a high sedimentation rate in the lake basin and likewise from Be-10 dating of glacial boulders. The maximum extent of the mountain glaciers during MIS 2 was attained prior to 24cal. ka BP. Some small present-day glaciers, which are now disappearing completely due to climate warming, were only slightly larger during the Last Glacial Maximum (LGM) as compared to AD 1953. A marked decrease in sedimentation rate around 18-17cal. ka BP indicates that the glaciers then became smaller and probably disappeared altogether around 15-14cal. ka BP.
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| 33. |
- Van Driel, Tim B., et al.
(author)
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Atomistic characterization of the active-site solvation dynamics of a model photocatalyst
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir 2 (dimen) 4 ] 2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.
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