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| 2. |
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| 3. |
- Astell, A. J., et al.
(författare)
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Developing a pragmatic evaluation of ICTs for older adults with cognitive impairment at scale : the IN LIFE experience
- 2022
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Ingår i: Universal Access in the Information Society. - Heidelberg, Germany : Springer. - 1615-5289 .- 1615-5297. ; 21:1, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Implementing information and communications technology (ICT) at scale requires evaluation processes to capture the impacton users as well as the infrastructure into which it is being introduced. For older adults living with cognitive impairment, thisrequires evaluation that can accommodate diferent levels of cognitive impairment, alongside input from family and formalcaregivers, plus stakeholder organisations. The European Horizon 2020 project INdependent LIving support Functions forthe Elderly (IN LIFE) set out to integrate 17 technologies into a single digital platform for older people living with cognitive impairment plus their families, care providers and stakeholders. The IN LIFE evaluation took place across six nationalpilot sites to examine a number of variables including impact on the users, user acceptance of the individual services andthe overall platform, plus the economic case for the IN LIFE platform. The results confrmed the interest and need amongolder adults, family caregivers, formal caregivers and stakeholders, for information and communications technology (ICT).Relative to the baseline, quality of life improved and cognition stabilised; however, there was an overall reluctance to payfor the platform. The fndings provide insights into existing barriers and challenges for adoption of ICT for older peopleliving with cognitive impairment.
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| 4. |
- Lindén, Anja, et al.
(författare)
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Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE) : a randomized multicentre feasibility trial
- 2024
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Ingår i: Critical care (London, England). - : BMC. - 1364-8535 .- 1466-609X. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care.METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion.RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation.CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible.TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.
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| 5. |
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| 6. |
- Astell, A. J., et al.
(författare)
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Developing a pragmatic evaluation of ICTs for older adults with cognitive impairment at scale: the IN LIFE experience
- 2021
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Ingår i: Universal Access in the Information Society. - Heidelberg, Germany : Springer. - 1615-5289 .- 1615-5297.
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Tidskriftsartikel (refereegranskat)abstract
- Implementing information and communications technology (ICT) at scale requires evaluation processes to capture the impact on users as well as the infrastructure into which it is being introduced. For older adults living with cognitive impairment, this requires evaluation that can accommodate different levels of cognitive impairment, alongside input from family and formal caregivers, plus stakeholder organisations. The European Horizon 2020 project INdependent LIving support Functions for the Elderly (IN LIFE) set out to integrate 17 technologies into a single digital platform for older people living with cognitive impairment plus their families, care providers and stakeholders. The IN LIFE evaluation took place across six national pilot sites to examine a number of variables including impact on the users, user acceptance of the individual services and the overall platform, plus the economic case for the IN LIFE platform. The results confirmed the interest and need among older adults, family caregivers, formal caregivers and stakeholders, for information and communications technology (ICT). Relative to the baseline, quality of life improved and cognition stabilised; however, there was an overall reluctance to pay for the platform. The findings provide insights into existing barriers and challenges for adoption of ICT for older people living with cognitive impairment.
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| 7. |
- Astell, A. J., et al.
(författare)
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INLIFE - Independent Living Support Functions for the Elderly: Technology and Pilot Overview
- 2018
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Ingår i: INTELLIGENT ENVIRONMENTS 2018. - 9781614998747 - 9781614998730 ; , s. 526-535
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we present the European H2020 project INLIFE (INdependent LIving support Functions for the Elderly). The project brought together 20 partners from nine countries with the goal of integrating into a common ICT platform a range of technologies intended to assist community-dwelling older people with cognitive impairment. The majority of technologies existed prior to INLIFE and a key goal was to bring them together in one place along with a number of new applications to provide a comprehensive set of services. The range of INLIFE services fell into four broad areas: Independent Living Support, Travel Support, Socialization and Communication Support and Caregiver Support. These included security applications, services to facilitate interactions with formal and informal caregivers, multilingual conversation support, web-based physical exercises, teleconsultations, and support for transport navigation. In total, over 2900 people participated in the project; they included elderly adults with cognitive impairment, informal caregivers, healthcare professionals, and other stakeholders. The aim of the study was to assess whether there was improvement/stabilization of cognitive/emotional/physical functioning, as well as overall well-being and quality of life of those using the INLIFE services, and to assess user acceptance of the platform and individual services. The results confirm there is a huge interest and appetite for technological services to support older adults living with cognitive impairment in the community. Different services attracted different amounts of use and evaluation with some proving extremely popular while others less so. The findings provide useful information on the ways in which older adults and their families, health and social care services and other stakeholders wish to access technological services, what sort of services they are seeking, what sort of support they need to access services, and how these services might be funded.
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| 8. |
- Pham, M. K., et al.
(författare)
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Certified Reference Material IAEA-446 for radionuclides in Baltic Sea seaweed
- 2014
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 87, s. 468-474
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Tidskriftsartikel (refereegranskat)abstract
- A Certified Reference Material (CRM) for radionuclides in seaweed (Fucus vesiculosus) from the Baltic Sea (IAEA-446) is described and the results of the certification process are presented. The K-40, Cs-132, U-234 and Pu239+240 radionuclides were certified for this material, and information values for 12 other radionuclides (Sr-90, Tc-99, Pb-210 (Po-210), Ra-226, Ra-228, Th-228, Th-230, Th-232, U-235, U-238, Pu-239 and Pu-240) are presented. The CRM can be used for Quality Assurance/Quality Control of analysis of radionuclides in seaweed and other biota samples, as well as for development and validation of analytical methods, and for training purposes. (C) 2013 Elsevier Ltd. All rights reserved.
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| 9. |
- Anderzen, J., et al.
(författare)
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International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
- 2020
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:4, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.
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| 10. |
- Chahla, J., et al.
(författare)
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Posterolateral corner of the knee: an expert consensus statement on diagnosis, classification, treatment, and rehabilitation
- 2019
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:8, s. 2520-2529
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo develop a statement on the diagnosis, classification, treatment, and rehabilitation concepts of posterolateral corner (PLC) injuries of the knee using a modified Delphi technique.MethodsA working group of three individuals generated a list of statements relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries to form the basis of an initial survey for rating by an international group of experts. The PLC expert group (composed of 27 experts throughout the world) was surveyed on three occasions to establish consensus on the inclusion/exclusion of each item. In addition to rating agreement, experts were invited to propose further items for inclusion or to suggest modifications of existing items at each round. Pre-defined criteria were used to refine item lists after each survey. Statements reaching consensus in round three were included within the final consensus document.ResultsTwenty-seven experts (100% response rate) completed three rounds of surveys. After three rounds, 29 items achieved consensus with over 75% agreement and less than 5% disagreement. Consensus was reached in 92% of the statements relating to diagnosis of PLC injuries, 100% relating to classification, 70% relating to treatment and in 88% of items relating to rehabilitation statements, with an overall consensus of 81%.ConclusionsThis study has established a consensus statement relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries. Further research is needed to develop updated classification systems, and better understand the role of non-invasive and minimally invasive approaches along with standardized rehabilitation protocols.Level of evidenceConsensus of expert opinion, Level V.
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| 11. |
- Chahla, J., et al.
(författare)
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The posteromedial corner of the knee: an international expert consensus statement on diagnosis, classification, treatment, and rehabilitation
- 2021
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 29, s. 2976-2986
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To establish recommendations for diagnosis, classification, treatment, and rehabilitation of posteromedial corner (PMC) knee injuries using a modified Delphi technique. Methods: A list of statements concerning the diagnosis, classification, treatment and rehabilitation of PMC injuries was created by a working group of four individuals. Using a modified Delphi technique, a group of 35 surgeons with expertise in PMC injuries was surveyed, on three occasions, to establish consensus on the inclusion or exclusion of each statement. Experts were encouraged to propose further suggestions or modifications following each round. Pre-defined criteria were used to refine item lists after each survey. The final document included statements reaching consensus in round three. Results: Thirty-five experts had a 100% response rate for all three rounds. A total of 53 items achieved over 75% consensus. The overall rate of consensus was 82.8%. Statements pertaining to PMC reconstruction and those regarding the treatment of combined cruciate and PMC injuries reached 100% consensus. Consensus was reached for 85.7% of the statements on anatomy of the PMC, 90% for those relating to diagnosis, 70% relating to classification, 64.3% relating to the treatment of isolated PMC injuries, and 83.3% relating to rehabilitation after PMC reconstruction. Conclusion: A modified Delphi technique was applied to generate an expert consensus statement concerning the diagnosis, classification, treatment, and rehabilitation practices for PMC injuries of the knee with high levels of expert agreement. Though the majority of statements pertaining to anatomy, diagnosis, and rehabilitation reached consensus, there remains inconsistency as to the optimal approach to treating isolated PMC injuries. Additionally, there is a need for improved PMC injury classification. Level of evidence: Level V. © 2020, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).
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| 12. |
- Geneid, A., et al.
(författare)
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Union of the European Phoniatricians position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020)
- 2020
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Ingår i: Journal of Laryngology and Otology. - : CAMBRIDGE UNIV PRESS. - 0022-2151 .- 1748-5460. ; 134:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- Background The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. Objectives This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. Conclusion As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.
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| 13. |
- Hellstrom-Lindberg, E., et al.
(författare)
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A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor : Significant effects on quality of life
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 120, s. 1037-
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Tidskriftsartikel (refereegranskat)abstract
- We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo = 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S-Epo > 500 U/l and =2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.
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| 14. |
- Ludvigsson, Johnny, et al.
(författare)
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Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:7, s. 1604-1612
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) <= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
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| 15. |
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| 16. |
- Simmen, K. A., et al.
(författare)
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Macrocylic inhibitors of hepatitis C virus
- 2012
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Patent (populärvet., debatt m.m.)abstract
- Inhibitors of HCV replication of formula (I)and the N-oxides, salts, and stereoisomers, whereineach dashed line represents an optional double bond;X is N, CH and where X bears a double bond it is C;R1 is —OR7, —NH—SO2R8;R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl;R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl;R4 is aryl or Het; n is 3, 4, 5, or 6;R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het;R6 is C1-6alkoxy, or dimethylamino;R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;aryl is phenyl optionally substituted with one, two or three substituents;Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents;pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
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| 17. |
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| 18. |
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| 19. |
- Barosi, G, et al.
(författare)
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Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms : consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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| 20. |
- Bengtsson, J., et al.
(författare)
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Quantum Szilard Engine with Attractively Interacting Bosons
- 2018
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Ingår i: Physical Review Letters. - 0031-9007. ; 120:10
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Tidskriftsartikel (refereegranskat)abstract
- We show that a quantum Szilard engine containing many bosons with attractive interactions enhances the conversion between information and work. Using an ab initio approach to the full quantum-mechanical many-body problem, we find that the average work output increases significantly for a larger number of bosons. The highest overshoot occurs at a finite temperature, demonstrating how thermal and quantum effects conspire to enhance the conversion between information and work. The predicted effects occur over a broad range of interaction strengths and temperatures.
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| 21. |
- Blomgren, E. M.V., et al.
(författare)
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Grey-box modeling for hot-spot temperature prediction of oil-immersed transformers in power distribution networks
- 2023
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Ingår i: Sustainable Energy, Grids and Networks. - 2352-4677. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Power transformers are one of the most costly assets in power grids. Due to increasing electricity demand and levels of distributed generation, they are more and more often loaded above their rated limits. Transformer ratings are traditionally set as static limits, set in a controlled environment with conservative margins. Through dynamic transformer rating, the rating is instead adapted to the actual working conditions of the transformers. This can help distribution system operators (DSOs) to unlock unused capacity and postpone costly grid investments. To this end, real-time information of the transformer operating conditions, and in particular of its hot-spot and oil temperature, is required. This work proposes a grey-box model that can be used for online estimation and forecasting of the transformer temperature. It relies on a limited set of non-intrusive measurements and was developed using experimental data from a DSO in Jutland, Denmark. The thermal model has proven to be able to predict the temperature of the transformers with a high accuracy and low computational time, which is particularly relevant for online applications. With a six-hour prediction horizon the mean average error was 0.4–0.6 °C. By choosing a stochastic data-driven modeling approach we can also provide prediction intervals and account for the uncertainty.
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| 22. |
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| 23. |
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| 24. |
- Hultcrantz, M., et al.
(författare)
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Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden
- 2020
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 287:4, s. 448-454
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Tidskriftsartikel (refereegranskat)abstract
- Background The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. Objective We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. Methods Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. Results A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. Conclusion The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.
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| 25. |
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| 26. |
- Louka, A S, et al.
(författare)
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The IL12B gene does not confer susceptibility to coeliac disease.
- 2002
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Ingår i: Tissue antigens. - 0001-2815. ; 59:1, s. 70-2
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease (CD) is a chronic inflammatory disorder where dietary gluten is not tolerated. In the lesion there are gluten reactive T cells predominantly secreting gamma-interferon. Both HLA and non-HLA genes contribute to CD susceptibility. Interleukin-12 (IL-12) regulates gamma-interferon production. The IL12B gene is located in a region (5q31.1-33.1) where there is evidence for linkage with CD. Allele 1 of an IL12B 3'UTR single-nucleotide polymorphism leads to increased expression of IL-12, and was recently implicated in susceptibility for type 1 diabetes (T1D). We found no evidence for association of allele 1 to CD by the transmission/disequilibrium test or case-control approach. No increased frequency was observed in patients belonging to families where the disease was linked to markers on chromosome 5q. Unlike T1D, allele 1 does not appear to confer susceptibility to CD.
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| 27. |
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| 28. |
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| 29. |
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| 31. |
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| 32. |
- Schwieler, L., et al.
(författare)
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Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients
- 2016
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. Methods: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). Results: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P < 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P < 0.0001) as well as a significantly increased QUIN/KYNA ratio (P < 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P < 0.05), kynurenine (P < 0.01), and QUIN (P < 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P < 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). Conclusions: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.
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| 33. |
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| 34. |
- Svanborg, Catharina, et al.
(författare)
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The 'innate' host response protects and damages the infected urinary tract
- 2001
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Ingår i: Annals of Medicine. - 1365-2060. ; 33:9, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.
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| 35. |
- Wiklander, M, et al.
(författare)
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Shame reactions after suicide attempt
- 2003
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Ingår i: Scandinavian journal of caring sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 17:3, s. 293-300
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Tidskriftsartikel (refereegranskat)
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| 36. |
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| 37. |
- Andersson, H.O., et al.
(författare)
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Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
- 2003
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
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| 38. |
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| 39. |
- Andreasson, M., et al.
(författare)
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Altered CSF levels of monoamines in hereditary spastic paraparesis 10 A case series
- 2019
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective To perform a comprehensive clinical characterization and biochemical CSF profile analyses in 2 Swedish families with hereditary spastic paraparesis (HSP) 10 (SPG10) caused by 2 different mutations in the neuronal kinesin heavy chain gene (KIF5A). Methods Structured clinical assessment, genetic studies, and neuroradiologic and electrophysiological evaluations were performed in 4 patients from 2 families with SPG10. Additional CSF analysis was conducted in 3 patients with regard to levels of neurodegenerative markers and monoamine metabolism. Results All patients exhibited a complex form of HSP with a mild to moderate concurrent axonal polyneuropathy. The heterozygous missense mutations c.767A>G and c.967C>T in KIF5A were found. Wide intrafamilial phenotype variability was evident in both families. CSF analysis demonstrated a mild elevation of neurofilament light (NFL) chain in the patient with longest disease duration. Unexpectedly, all patients exhibited increased levels of the dopamine metabolite, homovanillic acid, whereas decreased levels of the noradrenergic metabolite, 3-methoxy-4-hydroxyphenylglycol, were found in 2 of 3 patients. Conclusions We report on CSF abnormalities in SPG10, demonstrating that NFL elevation is not a mandatory finding but may appear after long-standing disease. Impaired transportation of synaptic proteins may be a possible explanation for the increased dopaminergic turnover and noradrenergic deficiency identified. The reasons for these selective abnormalities, unrelated to obvious clinical features, remain to be explained. Our findings need further confirmation in larger cohorts of patients harboring KIF5A mutations.
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| 40. |
- Andreasson, M., et al.
(författare)
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Parkinson's disease with restless legs syndrome-an in vivo corneal confocal microscopy study
- 2021
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Ingår i: npj Parkinson's Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Small fiber neuropathy (SFN) has been suggested as a trigger of restless legs syndrome (RLS). An increased prevalence of peripheral neuropathy has been demonstrated in Parkinson's disease (PD). We aimed to investigate, in a cross-sectional manner, whether SFN is overrepresented in PD patients with concurrent RLS relative to PD patients without RLS, using in vivo corneal confocal microscopy (IVCCM) and quantitative sensory testing (QST) as part of small fiber assessment. Study participants comprised of age- and sex-matched PD patients with (n = 21) and without RLS (n = 21), and controls (n = 13). Diagnosis of RLS was consolidated with the sensory suggested immobilization test. Assessments included nerve conduction studies (NCS), Utah Early Neuropathy Scale (UENS), QST, and IVCCM, with automated determination of corneal nerve fiber length (CNFL) and branch density (CNBD) from wide-area mosaics of the subbasal nerve plexus. Plasma neurofilament light (p-NfL) was determined as a measure of axonal degeneration. No significant differences were found between groups when comparing CNFL (p = 0.81), CNBD (p = 0.92), NCS (p = 0.82), and QST (minimum p = 0.54). UENS scores, however, differed significantly (p = 0.001), with post-hoc pairwise testing revealing higher scores in both PD groups relative to controls (p = 0.018 and p = 0.001). Analysis of all PD patients (n = 42) revealed a correlation between the duration of l-dopa therapy and CNBD (rho = -0.36, p = 0.022), and p-NfL correlated with UENS (rho = 0.35, p = 0.026) and NCS (rho = -0.51, p = 0.001). Small and large fiber neuropathy do not appear to be associated with RLS in PD. Whether peripheral small and/or large fiber pathology associates with central neurodegeneration in PD merits further longitudinal studies.
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| 41. |
- Appelros, P, et al.
(författare)
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A national stroke quality register : 12 years experience from a participating hospital
- 2007
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 14:8, s. 890-894
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Tidskriftsartikel (refereegranskat)abstract
- Registration of all hospitalized stroke patients is practiced in Sweden in order to assess care quality. Data in this register, Riks-Stroke (RS), may be biased due to incomplete registration. The purpose of this paper was to report changes in stroke outcome in relation to fluctuations in registration. Patients registered in RS at a hospital during the period 1994-2005 were analyzed. Case fatality at 28 days, living conditions, and activities of daily living (ADL) performance at 3 months were correlated to the number of patients registered and follow-up frequency. A total of 4994 stroke cases were registered during the period. A high annual registration rate was significantly correlated to a high case fatality ratio. A low annual follow-up rate was associated with a low proportion of patients living in their own home without any need of help. Quality parameters are sensible for selection bias, which make them difficult to compare over time and between hospitals. We suggest that by weighing outcome data against stroke severity, safer conclusions may be drawn. Additionally, hospitals considering setting up quality registers should make every effort to attain complete case ascertainment at all times, including patients managed outside the hospital, in order to avoid selection bias.
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| 42. |
- Ascione, F., et al.
(författare)
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Experience-optimised fast track improves outcomes and decreases complications in total knee arthroplasty
- 2020
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Ingår i: Knee. - : Elsevier BV. - 0968-0160. ; 27, s. 500-508
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to describe an advanced total knee arthroplasty (TKA) fast-track programme and determine discharge parameters during hospitalisation, as well as patient satisfaction, outcomes and complications within the first 12months after surgery. Methods This prospective study was based on patients selected consecutively for primary elective TKA, undergoing surgery between 2014 and 2017 in an established fast-track setting. Hospitalisation-related parameters were collected: demographics, body mass index (BMI), surgical time, ischaemia time, haemoglobin values, blood transfusions, length of stay, weight-bearing and stair-climbing time, opioid administration, preoperative and discharge loss of extension and maximum active flexion of the knee, visual analogue scale (VAS), 12-month follow-up satisfaction rate and range of motion, any complications, hospital re-admission and re-operation within the first 12months. Differences were determined using t-tests. Results A total of 704 total knee replacements implanted in 481 patients were included in the study and 223 patients had a bilateral TKA. Their mean age was 69.8years (range 57–88years). At the 12-month follow-up, 623 patients (88.5%) reported being satisfied or very satisfied and 15 (2.1%) were dissatisfied with their TKA, mean active flexion and loss of extension were 104.4° and 2.3°, respectively. A total of 15 complications occurred (two percent): five painful knees, three knee stiffness, three haematomas, two infections, one hospital re-admission and one deep venous thrombosis. No cases of pulmonary embolism and death related to surgery were reported. Conclusion The study reports on an advanced fast-track programme for TKA with a low incidence of surgery- and hospitalisation-related issues and complications and without any severe adverse events during the first year. On average, the fast-track programme had a short length of stay, an early recovery of weight-bearing, knee mobility, pain control and a high satisfaction rate, accompanied with an acceptable 12month range of motion.
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| 43. |
- Bateman, Alex, et al.
(författare)
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RNAcentral: A vision for an international database of RNA sequences.
- 2011
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Ingår i: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 17:11, s. 1941-6
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Tidskriftsartikel (refereegranskat)abstract
- During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor.
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| 44. |
- Battista, Francesca, et al.
(författare)
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Quantum Heat Fluctuations of Single-Particle Sources
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 110:12
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Tidskriftsartikel (refereegranskat)abstract
- Optimal single electron sources emit regular streams of particles, displaying no low-frequency charge current noise. Because of the wave packet nature of the emitted particles, the energy is, however, fluctuating, giving rise to heat current noise. We investigate theoretically this quantum source of heat noise for an emitter coupled to an electronic probe in the hot-electron regime. The distribution of temperature and potential fluctuations induced in the probe is shown to provide direct information on the single-particle wave function properties and display strong nonclassical features. DOI: 10.1103/PhysRevLett.110.126602
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| 45. |
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| 46. |
- Bjorkholm, M., et al.
(författare)
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Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms
- 2011
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology: JCO. - 0732-183X .- 1527-7755. ; 29:17, s. 2410-2415
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors. © 2011 by American Society of Clinical Oncology.
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| 47. |
- Burn, Garth L., et al.
(författare)
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Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity
- 2016
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 9:448
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Tidskriftsartikel (refereegranskat)abstract
- Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins. Superresolution imaging revealed that PTPN22-R620 (wild-type PTPN22) was present as large clusters in unstimulated T cells and that these disaggregated upon stimulation of LFA-1, enabling increased association of PTPN22 with its binding partners at the leading edge. The failure of PTPN22-R620W molecules to be retained at the leading edge led to increased LFA-1 clustering and integrin-mediated cell adhesion. Our data define a previously uncharacterized mechanism for fine-tuning integrin signaling in T cells, as well as a paradigm of auto-immunity in humans in which disease susceptibility is underpinned by inherited phosphatase mutations that perturb integrin function. 2016
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| 48. |
- Bybrant, M. C., et al.
(författare)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
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| 49. |
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