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  • Nyholm, T., et al. (författare)
  • A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
  • 2016
  • Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
  • Bach, Anders, et al. (författare)
  • A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage
  • 2012
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:9, s. 3317-3322
  • Tidskriftsartikel (refereegranskat)abstract
    • Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
  • Kristensen, K., et al. (författare)
  • Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies
  • 2019
  • Ingår i: Diabetologia. - : Springer. - 0012-186X. ; 62:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. Methods: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5–7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. Results: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. Conclusions/interpretation: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high. © 2019, The Author(s).
  • Mahajan, Anubha, et al. (författare)
  • Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 46:3, s. 234-234
  • Tidskriftsartikel (refereegranskat)abstract
    • To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
  • Almered Olsson, Gunilla, 1951, et al. (författare)
  • Peri-Urban Food Production and Its Relation to Urban Resilience
  • 2016
  • Ingår i: Sustainability. - 2071-1050. ; 8:12, s. 1340- 1361
  • Tidskriftsartikel (refereegranskat)abstract
    • Food production on the urban–rural fringe is under pressure due to competing land uses. We discuss the potential to improve resilience for urban–rural regions by enhancing food production as part of multifunctional land use. Through studies of peri-urban land in the regions of Gothenburg (Sweden), Copenhagen (Denmark) and Gent (Belgium), recent developments are analysed. Arable farming has been declining since 2000 in all three areas due to urban expansion and recreational land use changes. In city plans, networks of protected areas and green spaces and their importance for human wellbeing have been acknowledged. Policies for farmland preservation in peri-urban settings exist, but strategies for local food production are not expressed in present planning documents. Among the diversity of peri-urban agricultural activities, peri-urban food production is a developing issue. However, the competing forms of land use and the continuing high dependence of urban food on global food systems and related resource flows reduces peri-urban food production and improvements in urban food security. The positive effects of local food production need to be supported by governance aiming to improve the urban–rural relationship. The paper discusses the resilience potential of connecting urban–rural regions and re-coupling agriculture to regional food production.
  • Angelin, Bo, et al. (författare)
  • Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome
  • 2015
  • Ingår i: Journal of Internal Medicine. - : Wiley: 12 months. - 0954-6820 .- 1365-2796. ; 277:3, s. 331-342
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLiver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia. MethodsWe performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200gday(-1) eprotirome or placebo for 12weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures. ResultsEprotirome treatment at 100 and 200g daily reduced serum LDL cholesterol levels by 235% and 31 +/- 4%, respectively, compared with 2 +/- 6% for placebo (Pless than0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients. ConclusionIn hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.
  • Bach, Anders, et al. (författare)
  • Design and synthesis of highly potent and plasma-stable dimeric inhibitors of the PSD-95-NMDA receptor interaction
  • 2009
  • Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH. - 1433-7851 .- 1521-3773. ; 48:51, s. 9685-9689
  • Tidskriftsartikel (refereegranskat)abstract
    • On the double: Dimerization of monomeric peptide ligands towards the PDZ domains of the protein PSD-95 (postsynaptic density 95) leads to potent inhibitors of protein-protein interactions with stability in blood plasma. Optimization of the length of the polyethylene glycol linker results in unprecedented affinity for inhibitors of the PDZ1-2 domain.
  • Behrens, Anders, et al. (författare)
  • The Computerized General Neuropsychological INPH Test (CoGNIT) revealed improvement in Idiopathic Normal Pressure Hydrocephalus (INPH) after shunt surgery
  • Annan publikation (övrigt vetenskapligt)abstract
    • BackgroundWe have developed the COmputerized General Neuropsychological INPH Test (CoGNIT) dedicated for patients with idiopathic normal pressure hydrocephalus (INPH). Previously, validity and reliability of included tests have been established. The aim was to evaluate the battery’s sensitivity to detect cognitive changes after shunt surgery in INPH patients.MethodsPreoperatively, thirty-one INPH patients were given CoGNIT, which includes tests assessing memory, executive functions, attention, manual dexterity and psychomotor speed. CoGNIT also includes the Geriatric Depression Scale (GDS). Re-examination was done four months after shunt surgery. Scores and test completion were examined and compared to healthy elderly (n=44).ResultsPreoperative INPH test results were significantly lower in all tests compared to healthy. Improvements after shunt surgery were seen in all cognitive domains: memory (Ten-word list test, p<0,01), executive functions (Stroop incongruent, (p<0.05), attention (Two choice reaction test, p<0.01), psychomotor speed (Stroop congruent, p<0.05) and manual dexterity (Four- finger tapping, p<0.01). No ceiling effects were observed. Depressive symptoms were more common in INPH versus healthy and did not change postoperatively. Preoperatively 81 % of INPH patients completed at least eight of the nine included test.ConclusionsCoGNIT is sensitive to cognitive impairment and to investigate changes after shunt surgery in INPH. Completion rates are good. CoGNIT has a potential to be useful in the cognitive assessment of INPH. 
  • Behrens, Anders, et al. (författare)
  • The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery
  • 2020
  • Ingår i: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 132:3, s. 733-740
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH.METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist.RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests).CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.
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