| 1. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 2. |
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| 3. |
- Wang, J., et al.
(författare)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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Ingår i: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Tidskriftsartikel (refereegranskat)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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| 4. |
- Andelin, M., et al.
(författare)
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Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.
- 2016
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Ingår i: Journal of Diabetes Science and Technology. - : Diabetes Technology Society. - 1932-2968. ; 10:4, s. 876-884
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)
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| 5. |
- Matuleviciene, Viktorija, et al.
(författare)
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A Clinical Trial of the Accuracy and Treatment Experience of the Dexcom G4 Sensor (Dexcom G4 System) and Enlite Sensor (Guardian REAL-Time System) Tested Simultaneously in Ambulatory Patients with Type 1 Diabetes
- 2014
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 16:11, s. 759-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Continuous glucose monitoring (CGM) is a tool widely used in the treatment of patients with type 1 diabetes. The purpose of the current study was to evaluate whether accuracy and patient treatment satisfaction differ between the Enlite (TM) (Medtronic MiniMed, Inc., Northridge, CA) and Dexcom((R)) (San Diego, CA) G4 PLATINUM CGM sensors. Subjects and Methods: Thirty-eight ambulatory patients with type 1 diabetes used the Dexcom G4 and Enlite sensors simultaneously for a minimum of 4 and maximum of 6 days. Patients measured capillary glucose levels with a HemoCue((R)) (angelholm, Sweden) system six to 10 times a day. In addition, two inpatient studies were performed between Days 1-3 and 4-6. Results: The mean absolute relative difference (MARD) in blood glucose for the Dexcom G4 was significantly lower (13.9%) than for the Enlite sensor (17.8%) (P<0.0001). The corresponding MARDs for Days 1-3 were 15.0% versus 19.4% (P=0.0027) and 13.6% versus 15.9% (P=0.026) for Days 4-6. For glucose levels in the hypoglycemic range (<4.0 mmol/L), the MARD for the Dexcom G4 was 20.0% compared with 34.7% for the Enlite (P=0.0041). On a visual analog scale (VAS) (0-100), patients rated the Dexcom G4 more favorably than the Enlite in 12 out of the 13 user experience questions. For example, more patients rated their experience with the Dexcom G4 as positive (VAS, 79.7 vs. 46.6; P<0.0001) and preferred to use it in their daily lives (VAS, 79.1 vs. 42.1; P<0.0001). Conclusions: The Dexcom G4 sensor was associated with greater overall accuracy than the Enlite sensor during initial (Days 1-3) and later (Days 4-6) use and for glucose levels in the hypoglycemic range. Patients reported a significantly more positive experience using the Dexcom G4 than the Enlite.
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| 6. |
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| 7. |
- Singh, A., et al.
(författare)
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High glucose causes dysfunction of the human glomerular endothelial glycocalyx
- 2011
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 300:1
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Tidskriftsartikel (refereegranskat)abstract
- The endothelial glycocalyx is a gel-like layer which covers the luminal side of blood vessels. The glomerular endothelial cell (GEnC) glycocalyx is composed of proteoglycan core proteins, glycosaminoglycan (GAG) chains, and sialoglycoproteins and has been shown to contribute to the selective sieving action of the glomerular capillary wall. Damage to the systemic endothelial glycocalyx has recently been associated with the onset of albuminuria in diabetics. In this study, we analyze the effects of high glucose on the biochemical structure of the GEnC glycocalyx and quantify functional changes in its protein-restrictive action. We used conditionally immortalized human GEnC. Proteoglycans were analyzed by Western blotting and indirect immunofluorescence. Biosynthesis of GAG was analyzed by radiolabeling and quantified by anion exchange chromatography. FITC-albumin was used to analyze macromolecular passage across GEnC monolayers using an established in vitro model. We observed a marked reduction in the biosynthesis of GAG by the GEnC under high-glucose conditions. Further analysis confirmed specific reduction in heparan sulfate GAG. Expression of proteoglycan core proteins remained unchanged. There was also a significant increase in the passage of albumin across GEnC monolayers under high-glucose conditions without affecting interendothelial junctions. These results reproduce changes in GEnC barrier properties caused by enzymatic removal of heparan sulfate from the GEnC glycocalyx. They provide direct evidence of high glucose-induced alterations in the GEnC glycocalyx and demonstrate changes to its function as a protein-restrictive layer, thus implicating glycocalyx damage in the pathogenesis of proteinuria in diabetes.
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| 8. |
- Singh, A., et al.
(författare)
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Reactive Oxygen Species Modulate the Barrier Function of the Human Glomerular Endothelial Glycocalyx
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Reactive oxygen species (ROS) play a key role in the pathogenesis of proteinuria in glomerular diseases like diabetic nephropathy. Glomerular endothelial cell (GEnC) glycocalyx covers the luminal aspect of the glomerular capillary wall and makes an important contribution to the glomerular barrier. ROS are known to depolymerise glycosaminoglycan (GAG) chains of proteoglycans, which are crucial for the barrier function of GEnC glycocalyx. The aim of this study is to investigate the direct effects of ROS on the structure and function of GEnC glycocalyx using conditionally immortalised human GEnC. ROS were generated by exogenous hydrogen peroxide. Biosynthesis and cleavage of GAG chains was analyzed by radiolabelling (S35 and 3H-glucosamine). GAG chains were quantified on GEnC surface and in the cell supernatant using liquid chromatography and immunofluorescence techniques. Barrier properties were estimated by measuring trans-endothelial passage of albumin. ROS caused a significant loss of WGA lectin and heparan sulphate staining from the surface of GEnC. This lead to an increase in trans-endothelial albumin passage. The latter could be inhibited by catalase and superoxide dismutase. The effect of ROS on GEnC was not mediated via the GAG biosynthetic pathway. Quantification of radiolabelled GAG fractions in the supernatant confirmed that ROS directly caused shedding of HS GAG. This finding is clinically relevant and suggests a mechanism by which ROS may cause proteinuria in clinical conditions associated with high oxidative stress.
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| 9. |
- Alwin, J, et al.
(författare)
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Health economic and process evaluation of AT interventions for persons with dementia and their relatives : A suggested assessment model
- 2007
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Ingår i: Technology and Disability. - 1055-4181. ; 19:2-3, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- There is growing interest in assistive technology (AT) as a means of enabling participation in everyday activities for persons with dementia and their relatives. Health economic assessment of AT in dementia is of importance due to the consequences of the disease for both patients and relatives and to the high societal costs for dementia care. The aim of this article is to outline a model for assessment of AT interventions for persons with dementia. The model expands existing assessment models as it also includes evaluation of the intervention process. Methodological challenges and possibilities in making health economic assessments, including outcomes and costs, as well as process evaluation, are discussed in the article.
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| 10. |
- Belyazid, Salim, et al.
(författare)
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A Sustainability Assessment of the Urban Rehabilitation Project of the Medina of Fez, Morocco
- 2003
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Ingår i: Proceedings of the 21st International Conference of the System Dynamics Society. - 9780967291482
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Konferensbidrag (refereegranskat)abstract
- The old city of Fez, Morocco, classified as Heritage of Humankind by the UNESCO, is subject to an integrated rehabilitation plan running over 15 years. The plan aims at restoring and preserving the economy, cultural value, and social heritage of the old city. The study follows a system dynamics approach to describe and analyze the rehabilitation plan in order to identify the strengths and defects of the plan. This study shows that while the plan is giving relatively satisfying results over the short and medium terms, it is unlikely to attain long term sustainability.
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