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- Hall, CL, et al.
(författare)
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Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e027583-
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Tidskriftsartikel (refereegranskat)abstract
- Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.Methods and analysisThis parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).Ethics and disseminationThe findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).Trial registration numbersISRCTN70758207andNCT03483493; Pre-results.
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- Nielsen, S. N., et al.
(författare)
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Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
- 2017
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Ingår i: Pediatr Blood Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 64:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. ProcedureWe retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]. ResultsAfter median 9.5 years (interquartile range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard-risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02-0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard-risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69-5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47). ConclusionsThe rate of second cancer was generally highest in patients with low-risk ALL, but we could not identify a subset at higher risk than others.
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- Popescu, A., et al.
(författare)
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Increasing transparency and privacy for online social network users – USEMP value model, scoring framework and legal
- 2016
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Ingår i: Privacy Technologies and Policy. - Cham : Encyclopedia of Global Archaeology/Springer Verlag. - 9783319314556 - 9783319314563 ; , s. 38-59
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Konferensbidrag (refereegranskat)abstract
- In this paper we present research results from the multi-disciplinary EU research project USEMP (USEMP is a project funded from EU research framework, additional information about project scope and deliverables are available at project’s public website at: http://www.usemp-project.eu/). In particular, we look at the legal aspects of personal data licensing and profile transparency, the development of a personal data value model in Online Social Networks (OSNs) and the development of disclosure scoring and personal data value frameworks. In the first part of the paper we show how personal data usage licensing and profile transparency for OSN activities provides for Data Protection by Design (DPbD). We also present an overview of the existing personal data monetization ecosystem in OSNs and its possible evolutions for increasing privacy and transparency for consumers about their OSN presence. In the last part of the paper, we describe the USEMP scoring framework for personal information disclosure and data value that can assist users to better perceive how their privacy is affected by their OSN presence and what the value of their OSN activities is.
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- Bersellini Farinotti, Alex, et al.
(författare)
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Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
- 2019
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
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| 12. |
- De Hert, S, et al.
(författare)
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Aprotinin: is it time to reconsider?
- 2015
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Ingår i: European journal of anaesthesiology. - 1365-2346. ; 32:9, s. 591-595
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Ding, Zhoujie, et al.
(författare)
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IgE-mediated enhancement of CD4(+) T cell responses requires antigen presentation by CD8 alpha(-) conventional dendritic cells
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4(+) T cell responses in vivo. The effects require the presence of CD23 (Fc epsilon-receptor II)(+) B cells, which capture IgE-complexed antigens (Ag) in the circulation and transport them to splenic B cell follicles. In addition, also CD11c(+) cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. To elucidate the nature of this dendritic cell, mice were immunized with ovalbumin (OVA)-specific IgE and OVA, and different populations of CD11c(+) cells, obtained from the spleens four hours after immunization, were tested for their ability to present OVA. CD8 alpha(-) conventional dendritic cells (cDCs) were much more efficient in inducing specific CD4(+) T cell proliferation ex vivo than were CD8 alpha(+) cDCs or plasmacytoid dendritic cells. Thus, IgE-Ag complexes administered intravenously are rapidly transported to the spleen by recirculating B cells where they are delivered to CD8 alpha(-) cDCs which induce proliferation of CD4(+) T cells.
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| 14. |
- Gottschalk Højfeldt, S, et al.
(författare)
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IgG Antibodies Cannot Explain Silent Inactivation in PEG-Asparaginase Treatment
- 2018
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Ingår i: Pediatric Blood & Cancer. 65 (S2), Abstracts from the 50th Congress of the International Society of Paediatric Oncology (SIOP) Kyoto, Japan November 16–19, 2018, e27455. PO-054. - : Wiley. - 1545-5009.
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Konferensbidrag (refereegranskat)abstract
- Background/Objectives: PEG-asparaginase represents a key element in the treatment of acute lymphoblastic leukemia (ALL), however allergic reactions and lack of asparaginase enzyme activity shortly after administration (silent inactivation) constitutes a significant challenge. Anti-PEG antibodies formed prior to PEG-asparaginase exposure are suggested to cause the latter accelerated clearance phenomenon. We investigated anti-PEG antibody responses before and during PEG-asparaginase therapy, in children treated according to NOPHO ALL2008 protocol, with and without silent inactivation and hypersensitivity. Design/Methods: PEG-asparaginase enzyme activity was determined in patients aged 1-17.9 years as part of the NOPHO ALL2008 protocol. These measurements were used to categorize patients with or without enzyme activity. In this case control study, recovery of spiked PEG-asparaginase activity after IgG complex depletion with protein G affinity chromatography was used to evaluate IgG antibodies to PEGasparaginase. 359 samples were analyzed from 40 patients with: i) no adverse phenotype (n=10), ii) silent inactivation (n=10), iii) allergy and asparaginase enzyme inactivation (n=10), iv) allergy and asparaginase enzyme activity (n=10) Results: No patients with PEG-asparaginase enzyme activity had or developed anti-PEG antibodies during treatment. Thus children with and without clinical allergy and enzyme activity could not be distinguished serologically. In contrast, IgG antibodies were detected in 19 of 20 of children without enzyme activity, regardless of allergy status. The lack of in vivo asparaginase enzyme activity was always displaying from the first PEG-asparaginase administration, but anti-PEG antibodies were only detected in pre-exposure samples in 2 of 38 patients (5%). 2 patients had missing pre-exposure samples. Conclusions: IgG responses to repeated PEG-asparaginase administrations are not the primary driver of PEGasparaginase inactivation. However these antibodies may accelerate the drug clearance. Further validation and investigation of IgM antibodies is warranted in order to gain more knowledge about the inactivation of PEG-asparaginase.
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| 15. |
- Gottschalk Højfeldt, S, et al.
(författare)
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Relapse Following Truncation of Asparaginase in NOPHO ALL2008
- 2019
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Ingår i: 38th NOPHO Annual meeting. Aalborg, Denmark 3-7 May.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Asparaginase related toxicities constitute a significant problem in the treatment of acute lymphoblastic leukemia (ALL); besides acute morbidity and mortality the toxicities can also cause truncation of treatment. Few studies have investigated relapse rates following asparaginase truncation, while taking asparaginase enzyme activity into account. The primary aim was to investigate if patients with truncation of asparaginase treatment or no enzyme activity (truncated) had a different risk of relapse compared to patients who had not been truncated and who had measurable enzyme activity (non-truncated). Children aged 1–17 years, diagnosed with non-high risk ALL July 2008 – March 2016 and treated according to the NOPHO ALL2008 protocol were eligible for inclusion. Excluding 140 patients with missing data, 1108 patients were included and followed from diagnosis with delayed entry at end of asparaginase treatment until relapse, competing events (death and secondary tumor), or end of follow-up. Median follow-up time was 5.54 years (interquartile range: 4.02–7.53). The 7-year cumulative incidence of relapse for the non-truncated was 6.68% (95% confidence interval [CI]: 4.72–8.63) and for the truncated 11.3% (95%CI: 7.01–15.7). The relapse-specific hazard ratio (HR) from a simple Cox regression comparing truncated vs. non-truncated was 1.76 (95%CI: 1.09–2.84, p=0.02). In a multiple analysis including MRD day 29, age group =/< 10 years, white blood cell count, and CNS status at diagnosis, the adjusted HR was 1.70 (95%CI: 1.05–2.74, p=0.03). Comparing patients who received <50% of their asparaginase doses with those who received =50% showed similar results (adjusted HR=1.84 (95%CI: 1.11–3.07, p=0.02)). No specific relapse type was found to be associated with asparaginase truncation. The relapse-specific hazard rate is significantly higher for children who had their asparaginase treatment truncated or had no enzyme activity. Our results confirm the importance of asparaginase in ALL treatment and emphasize the importance of therapeutic drug monitoring.
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- Lindholm, Miranda S., et al.
(författare)
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Glacial geomorphology of the Maidika region, Tibetan Plateau
- 2016
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Ingår i: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 12:5, s. 797-803
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Tidskriftsartikel (refereegranskat)abstract
- We present a glacial geomorphological map at a scale of 1: 200,000 of the Maidika region in the southeastern part of the central Tibetan Plateau covering 13,600 km(2). Based on the 90 m resolution SRTM elevation model, the 30 m resolution ASTER GDEM elevation model, and the Landsat ETM+ satellite imagery of 30/15 m resolution, we have mapped glacial valleys, marginal moraines, glacial lineations, and hummocky terrain. Glacial landforms occur frequently and indicate extensive past glaciation with alpine style valley glaciers as well as more extensive ice fields. Of particular interest is the presence of glacial lineation swarms, which is unusual for the Tibetan Plateau glacial landform record. Based on the distribution of glacial landforms, we present a generalized maximum glacial extent reconstruction covering 6045 km(2) or 44% of the map.
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| 17. |
- Liu, Lisa L., et al.
(författare)
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Ex Vivo Expanded Adaptive NK Cells Effectively Kill Primary Acute Lymphoblastic Leukemia Cells
- 2017
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Ingår i: CANCER IMMUNOLOGY RESEARCH. - 2326-6066 .- 2326-6074. ; 5:8, s. 654-665
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Tidskriftsartikel (refereegranskat)abstract
- Manipulation of human natural killer (NK) cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIR), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL). Culture of polyclonal NK cells together with feeder cells expressing HLA-E, the ligand for the activating NKG2C receptor, led to selective expansion of adaptive NK cells with enhanced allor-eactivity against HLA-mismatched targets. The ex vivo expanded adaptive NK cells gradually obtained a more differentiated phenotype and were specific and highly efficient killers of allogeneic pediatric T-and precursor B-cell acute lymphoblastic leukemia (ALL) blasts, previously shown to be refractory to killing by autologous NK cells and the NK-cell line NK92 currently in clinical testing. Selective expansion of NK cells that express one single inhibitory KIR for self-HLA class I would allow exploitation of the full potential of NK-cell alloreactivity in cancer immunotherapy. In summary, our data suggest that adaptive NK cells may hold utility for therapy of refractory ALL, either as a bridge to transplant or for patients that lack stem cell donors.
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| 20. |
- Oskarsson, T., et al.
(författare)
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Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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- Schönning, A., et al.
(författare)
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Venous thrombosis in children and adolescents with Hodgkin lymphoma in Sweden
- 2017
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 152, s. 64-68
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Pediatric patients with Hodgkin lymphoma (HL) have several risk factors for venous thromboembolism (VTE). Although these patients are occasionally treated with thromboprophylaxis, no guidelines are implemented in Sweden. Scarce data from adult patients indicate an increased risk of VTE, but pediatric data is largely missing. Given the favorable overall survival of HL, there should reasonably be more focus on preventing complications. Materials and methods We conducted a retrospective cohort study, including all patients registered in the Childhood Cancer Registry under the age of 18 years diagnosed with HL between January 2005 and December 2015 in Sweden. Results Data was retrieved from the medical records of all 163 patients (100%) at six Swedish pediatric cancer centers. The incidence of VTE was 7.7% (symptomatic VTE 3.9%). The median follow-up was 3.4 years (range 0.3–10.5). Only five patients (3.1%) were treated with thromboprophylaxis. All VTE events occurred in the older age category (11–17 years) and all but one (92.7%) had a mediastinal mass. While the VTE did not significantly affect the treatment of HL, it caused increased morbidity and 2/12 developed a post-thrombotic syndrome. No significant risk factors for VTE were identified. Conclusions VTE is a relatively common complication of HL and its treatment, causing increased acute and long-term morbidity. However, due to limited number of events we could not demonstrate risk-factors for VTE that would identify patients who might benefit from thromboprophylaxis.
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| 28. |
- Tie, H, et al.
(författare)
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Cost-effectiveness analysis of telephone cognitive-behaviour therapy for adolescents with obsessive-compulsive disorder
- 2019
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Ingår i: BJPsych open. - : Royal College of Psychiatrists. - 2056-4724. ; 5:1, s. e7-
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Tidskriftsartikel (refereegranskat)abstract
- Telephone cognitive–behaviour therapy (TCBT) may be a cost-effective method for improving access to evidence-based treatment for obsessive–compulsive disorder (OCD) in young people.AimsEconomic evaluation of TCBT compared with face-to-face CBT for OCD in young people.MethodRandomised non-inferiority trial comparing TCBT with face-to-face CBT for 72 young people (aged 11 to 18) with a diagnosis of OCD. Cost-effectiveness at 12-month follow-up was explored in terms of the primary clinical outcome (Children's Yale-Brown Obsessive-Compulsive Scale, CY-BOCS) and quality-adjusted life-years (QALYs) (trial registration: ISRCTN27070832).ResultsTotal health and social care costs were higher for face-to-face CBT (mean total cost £2965, s.d. = £1548) than TCBT (mean total cost £2475, s.d. = £1024) but this difference was non-significant (P = 0.118). There were no significant between-group differences in QALYs or the CY-BOCS and there was strong evidence to support the clinical non-inferiority of TCBT. Cost-effectiveness analysis suggests a 74% probability that face-to-face CBT is cost-effective compared with TCBT in terms of QALYs, but the result was less clear in terms of CY-BOCS, with TCBT being the preferred option at low levels of willingness to pay and the probability of either intervention being cost-effective at higher levels of willingness to pay being around 50%.ConclusionsAlthough cost-effectiveness of TCBT was sensitive to the outcome measure used, TCBT should be considered a clinically non-inferior alternative when access to standard clinic-based CBT is limited, or when patient preference is expressed.Declaration of interestD.M.-C. reports research grants from the Swedish Research Council (Vetenskapsrådet), the Swedish Research Council for Health, working life and welfare (Forte), the US National Institute of Mental Health (NIMH), the UK National Institute of Health Research (NIHR), as well as royalties from Wolters Kluwer Health and Elsevier, all unrelated to the submitted work.
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