| 1. |
- Asplund, Stig-Börje, 1973-
(författare)
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Läsning som identitetsskapande handling. : Gemenskapande och utbrytningsförsök i fordonspojkars litteratursamtal.
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this dissertation literature discussions which include students of Vehicle Engineering at a Swedish upper secondary school will be discussed. The students are all boys. The study is focused on these boys’ small-group literature discussions, and the aim of the study is to describe what happens when they discuss four of the novels that form an integral part in the context of their Swedish studies. Principal fields of interest are the readings and the reception that the boys give utterance to in the literature discussions, as well as the identity-constructing processes which set in when they interact in the light of what they have read.The empirical material consists of eleven video recorded small-group discussions, and a conversational analytic perspective is combined with a reception theory perspective in the dissertation.The study shows that a sense of community is vital to the core of the boys’ literature discussions, and this has an influence on the reception and the readings that come up in the discussions. The boys are anxious to come to an agreement and voices which threaten to shatter the sense of community that has been constructed in the discussions are opposed in different ways. The literature discussions are not only arenas where the boys construct themselves as readers but are also considered as a forum where various identity-constructing practices take place.As readers these boys are bound to what can be read, and what cannot be read, in literary texts, but it is possible to see a certain development in their readings towards a more complex attitude, such as they find expression in the discussions. The boys also carry out the literature discussions, and the constructed sense of community is based on the reading of the novel to be discussed in a small-group discussion. Thus the boys take on the responsibility for their own learning as well.Many of the processes in which the boys are involved during the literature discussions could be described as processes of social reproduction, but various dividing lines which could be identified in the study also show that there are openings for other directions of the discussions.
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| 2. |
- Alam, Assad, et al.
(författare)
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Cooperative driving according to Scoop
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- KTH Royal Institute of Technology and Scania are entering the GCDC 2011 under the name Scoop –Stockholm Cooperative Driving. This paper is an introduction to their team and to the technical approach theyare using in their prototype system for GCDC 2011.
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| 3. |
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| 4. |
- Amisten, Stefan, et al.
(författare)
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Activation of imidazoline receptor I-2, and improved pancreatic beta-cell function in human islets
- 2018
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727. ; 32:9, s. 813-818
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The impact of BL11282, an imidazoline receptor (NISCH) agonist, on potentiation of glucose-stimulated insulin secretion (GSIS) from isolated human non-diabetic (ND) and type 2 diabetic (T2D) islets was investigated. Methods: Analysis of mRNA was performed by RNA-sequencing and qPCR Insulin and cAMP by RIA and EUSA respectively. Results: RNA-sequencing data revealed that NISCH is highly expressed in fat tissues, islets, liver and muscles, with eight detectable splice variants of transcripts in islets. NISCH had a positive correlation with GLP-1 (GLP1R) and GIP (GIPR) receptor transcripts. The expression of NISCH was confirmed by qPCR in human islets. NISCH and GLP1R were comparably higher expressed in mouse islets compared to human islets. GSIS was dose-dependently potentiated by BL11282 from incubated islets of ND and T2D human islet donors. The insulinotropic action of BL11282 was associated with increased cAMP. While the harmful effect of high glucose on reductive capacity of islet cells was enhanced by glibenclamide during long-term culture, it was counteracted by BL11282 or Bt2-cAMP. BL11282 also increased proliferation of INS-1 cells during long-time culture. Conclusion: Our data suggest that BL11282 potentiates GSIS by an action involving cAMP/PKA system and BL11282 could be an attractive insulinotropic and beta-cell protective agent. (C) 2018 Elsevier Inc. All rights reserved.
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| 5. |
- Andersson, J. Y., et al.
(författare)
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Quantum structure based infrared detector research and development within Acreo's centre of excellence IMAGIC
- 2010
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Ingår i: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 53:4, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- Acreo has a long tradition of working with quantum structure based infrared (IR) detectors and arrays. This includes QWIP (quantum well infrared photodetector), QDIP (quantum dot infrared photodetector), and InAs/GaInSb based photon detectors of different structure and composition. It also covers R&D on uncooled microbolometers. The integrated thermistor material of such detectors is advantageously based on quantum structures that are optimised for high temperature coefficient and low noise. Especially the SiGe material system is preferred due to the compatibility with silicon technology. The R&D work on IR detectors is a prominent part of Acreo's centre of excellence "IMAGIC" on imaging detectors and systems for non-visible wavelengths. IMAGIC is a collaboration between Acreo, several industry partners and universities like the Royal Institute of Technology (KTH) and Linkoping University. (C) 2010 Elsevier B.V. All rights reserved.
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| 6. |
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| 7. |
- Asplund, Matthias, et al.
(författare)
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Condition monitoring of rolling stock wheels : approach towards maintenance decision making
- 2014
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Ingår i: 27th International Congress on Condition Monitoring and Diagnostic Engineering (COMADEM 2014). - : COMADEM International.
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Konferensbidrag (refereegranskat)abstract
- Due to the more or less fixed inherent capacity of a railway system, capacity consuming events like failures within a railway network should be kept to a minimum. This could be achieved by the use of existing and new condition monitoring systems which can detect, report and predict failure events in an early stage. Demands for higher service quality, higher capacity, network availability and track quality together with less human intervention on tracks, drive the development of railway condition monitoring systems.Failure driven capacity consumption due to worn or defected rolling stock wheels have a big impact on the capacity and the infrastructure condition. Wheel defects such as out-of-round wheels, generates high forces, and could result in large capacity consumption especially for areas with cold climate conditions. Bad wheels cause even higher track wear that reduce the life length of the track. Wheels with fatigue defects could also influence the track safety issues. This paper presents how different wheel defects can be monitored; together with a review of the most common wayside condition monitoring systems on the Swedish railway network. The study also describes how the decision making process could take advantage of the condition monitoring data in order to increase the achieved network capacity.
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| 8. |
- Asplund, Olof
(författare)
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Data integration and visualization in type 2 diabetes research and care: From biological mechanisms to precision medicine.
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Type 2 diabetes (T2D) is a complex heterogeneous disorder affecting multiple organs. Gene expression studies in organs central to T2D, such as pancreatic islets and skeletal muscle will help elucidate and disentangle molecular mechanisms underlying T2D. Deep phenotyping using commonly measured clinical variables allows for the identification of clinically relevant T2D subgroups, representing a step towards individualized medicine. Creation and use of interactive, web-based tools can facilitate the application of these findings by researchers and clinicians.Aim. To analyze and investigate diabetes-related aberrations in gene expression in skeletal muscle and islets using bioinformatics approaches. To expand methodologies for diabetes sub-classification using anthropometric and biomarker data from T2D patients for clinical application. Toc reate and refine novel web applications providing unique resources for investigation of the metabolic abnormalities occurring in diabetes. Methods. In paper I, curated, public skeletal muscle microarray gene expression data were used to analyze alterations in gene expression in relation to diabetes-related phenotypes such as BMI, T2D and age. In Paper II, RNA sequencing data on human islets from 188 donors were used to analyze the association between gene expression and diabetes status, BMI, and HbA1c, among other diabetes-related phenotypes. In paper III, a combined analysis of human islets from 420 donors were used to investigate the relationship between genetic variation and gene expression. In paper IV, a total of 43 samples from islet, liver, kidney and skin from human embryos/fetuses between 7-14 weeks post conception were sequenced using RNA sequencing. Gene expression of fetal tissues in relation to corresponding tissues in adults from GTEx were used to identify genes important in development. In paper V, clinical data including age of onset, sex, BMI, HbA1c, HOMA2IR, HOMA2B, and GAD antibodies collected at diagnosis from 8,406 T2D patients were used to implement a novel model of classification of T2D based on previously-published findings. Results. In Paper I, phenotype data and gene expression data, as well as differential expression analyses of age, gender, diabetes, and acute training was used to create MuscleAtlasExplorer, an interactive data visualization web application providing complex functions for analysis of gene expression and phenotype data in skeletal muscle. In Paper II, a web application for gene look-ups, IsletGeneView, was created, providing gene-centric information for researchers with gene expression in human islets in relation to diabetes, HbA1c, BMI and co-expression with secretory genes, elucidating the complex phenotype-gene expression relationship in diabetic islets. In paper III, novel eQTLs in human islets were identified, increasing the insight into genetic variants influencing gene expression in human islets. In paper IV, FLEET was created, a web application atlas of gene expression in human fetal and adult islets, kidney, liver and skin. In paper V, a novel method for diabetes sub-classification with confidence scoring was devised and implemented. A novel software system for sub-classification of diabetes was created incorporating the sub-classification method, allowing for automatic classification of patients and entire diabetes research cohorts. Conclusion. Taken together, this thesis shows the possibilities of using data visualization and web development to create resources for elucidating biological mechanisms underlying T2D. The resulting data is readily applicable and can be used to support functional studies. Furthermore, an automated system for diabetes sub-classification is presented and can facilitate support to clinicians, representing a first step towards individualized therapy.
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| 9. |
- Asplund, Olof, et al.
(författare)
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Islet Gene View-a tool to facilitate islet research
- 2022
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.
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| 10. |
- Asplund, Olof, et al.
(författare)
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MuscleAtlasExplorer : a web service for studying gene expression in human skeletal muscle
- 2020
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Ingår i: Database: the journal of biological databases and curation. - : Oxford University Press (OUP). - 1758-0463. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- MuscleAtlasExplorer is a freely available web application that allows for the exploration of gene expression data from human skeletal muscle. It draws from an extensive publicly available dataset of 1654 skeletal muscle expression microarray samples. Detailed, manually curated, patient phenotype data, with information such as age, sex, BMI and disease status, are combined with skeletal muscle gene expression to provide insights into gene function in skeletal muscle. It aims to facilitate easy exploration of the data using powerful data visualization functions, while allowing for sample selection, in-depth inspection and further analysis using external tools. Availability: MuscleAtlasExplorer is available at https://mae.crc.med.lu.se/mae2 (username 'muscle' and password 'explorer' pre-publication).
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| 11. |
- Basile, Anna Maria, et al.
(författare)
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Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes
- 2006
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Ingår i: CEREBROVASCULAR DISEASES. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. <i>Methods:</i> The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. <i>Results:</i> Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. <i>Conclusions:</i> The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
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| 12. |
- Basile, Anna Maria, et al.
(författare)
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Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.
- 2006
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Ingår i: Cerebrovasc Dis. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-22
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. <i>Methods:</i> The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. <i>Results:</i> Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. <i>Conclusions:</i> The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
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| 13. |
- Bertonnier-Brouty, Ludivine, et al.
(författare)
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E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma
- 2024
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Ingår i: Cancer Medicine. - 2045-7634. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs.OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion.METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells.CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.
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| 14. |
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| 15. |
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| 16. |
- Dunér, Pontus, et al.
(författare)
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Adhesion G Protein-Coupled Receptor G1 (ADGRG1/GPR56) and Pancreatic beta-Cell Function
- 2016
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:12, s. 4637-4645
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Tidskriftsartikel (refereegranskat)abstract
- Context: Adhesion G protein-coupled receptor (GPCR)-G1 (ADGRG1) is the most abundant GPCR in human pancreatic islets, but its role in islet function is unclear. Objective: Investigate how ADGRG1 expression and activation by its ligand, collagen III, impacts beta-cell function in normal and type 2 diabetic (T2D) islets. Design: Genes associated with the ADGRG1 in human islets was probed by RNA-sequencing of human pancreatic islet isolated from cadaveric donors, followed by functional studies on beta-cell proliferation, apoptosis, and insulin secretion in human and mouse islets and in INS-1 cells. Main Outcome Measures: Changes in beta-cell gene expression, proliferation, apoptosis, and insulin secretion were quantified by RNA-sequencing, qPCR, Thymidine incorporation, Western blotting, and RIA, respectively. Results: ADGRG1 is the most abundant GPCR mRNA in both human and mouse islets, and its expression in human islets strongly correlates with genes important for beta-cell function and T2D risk. The expression of ADGRG1 was reduced in islets of T2D donors, in db/db mouse islets, and in isolated human islets exposed to chronic hyperglycemia. Beneficial effects of collagen type III on beta-cell function via activation of the cAMP/protein kinase A pathway, suppression of RhoA and caspase-3 activity, increased beta-cell viability, and proliferation were abolished when ADGRG1 was down-regulated in beta-cells. Conclusions: We demonstrate a mechanistic link between ADGRG1 expression and beta-cell function. Pharmacological agents that promote expression or activation of the ADGRG1 receptor may represent a novel approach for the treatment of T2D.
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| 17. |
- Eriksson, Olof, et al.
(författare)
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5-Fluoro-[beta-C-11]-L-tryptophan is a functional analogue of 5-hydroxy-[beta-C-11]-L-tryptophan in vitro but not in vivo
- 2013
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 40:4, s. 567-575
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: 5-Hydroxy-[β-(11)C]-L-tryptophan ([(11)C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[(18)F]Fluoro-L-tryptophan ([(18)F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[(18)F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β-(11)C]-L-tryptophan ([(11)C]FTRP), based on the existing chemo-enzymatic method for [(11)C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [(11)C]HTP.METHODS: The in vitro and in vivo behavior of [(11)C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [(11)C]HTP was used for direct comparison.RESULTS: Uptake of [(11)C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [(11)C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway.CONCLUSION: [(11)C]FTRP has in vitro biological function similar to that of [(11)C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [(11)C]HTP in PET imaging in oncology, neurology or diabetes.
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| 18. |
- Fedotkina, Olena, et al.
(författare)
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Novel Reclassification of Adult Diabetes Is Useful to Distinguish Stages of β-Cell Function Linked to the Risk of Vascular Complications : The DOLCE Study From Northern Ukraine
- 2021
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Presently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and risk of vascular complications. The current study aimed to characterize new subgroups of adult diabetes using this strategy in a defined population from northern Ukraine. Methods: We analyzed 2,140 patients with established diabetes from the DOLCE study (n = 887 with new-onset diabetes and n = 1,253 with long duration). We used the k-means approach to perform clustering analyses using BMI, age at onset of diabetes, HbA1c, insulin secretion (HOMA2-B), and insulin resistance (HOMA2-IR) indices and glutamic acid decarboxylase antibodies (GADA) levels. Risks of macro- (myocardial infarction or stroke) and microvascular [retinopathy, chronic kidney disease (CKD) and neuropathy] complications and associations of genetic variants with specific clusters were studied using logistic regression adjusted for age, sex, and diabetes duration. Results: Severe autoimmune diabetes (SAID, 11 and 6%) and severe insulin-deficient diabetes (SIDD, 25 and 14%) clusters were twice as prevalent in patients with long-term as compared to those with new-onset diabetes. Patients with long duration in both SAID and SIDD clusters had highest risks of proliferative retinopathy, and elevated risks of CKD. Long-term insulin-resistant obese diabetes 1 (IROD1) subgroup had elevated risks of CKD, while insulin-resistant obese diabetes 2 (IROD2) cluster exhibited the highest HOMA2-B, lowest HbA1c, and lower prevalence of all microvascular complications as compared to all other clusters. Genetic analyses of IROD2 subgroup identified reduced frequency of the risk alleles in the TCF7L2 gene as compared to all other clusters, cumulatively and individually (p = 0.0001). Conclusion: The novel reclassification algorithm of patients with adult diabetes was reproducible in this population from northern Ukraine. It may be beneficial for the patients in the SIDD subgroup to initiate earlier insulin treatment or other anti-diabetic modalities to preserve β-cell function. Long-term diabetes cases with preserved β-cell function and lower risk for microvascular complications represent an interesting subgroup of patients for further investigations of protective mechanisms.
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| 19. |
- Hatem, Gad, et al.
(författare)
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Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming
- 2022
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 107:5, s. 1303-1316
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function.RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers.CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.
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| 20. |
- Hellzén, Ove, et al.
(författare)
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From optimism to pessimism : A case study of a psychiatric patient
- 1998
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 7:4, s. 360-370
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Tidskriftsartikel (refereegranskat)abstract
- This article focuses on the results of a single case study which illuminates an understanding of phases in nursing care for a patient in a psychiatric setting in Sweden. The focus of this study is a fifty year old man who showed progressive deterioration from increased motor activity to oral, sexual, destructive and aggressive actions. The data collection using five methods occurred during a 21 months period. Results of the content analyses processes identified four distinct but indiscreet phases of the patient’s complex condition. The medical and nursing care was categorised in three approaches: optimistic, strategic and resigned. The results raise the question whether there is action that is without any meaning as an expression of the patient´s wishes, thoughts and feelings. It seems clear that the patient in this study felt really angry and in despair. However, during moments of lucidity, he also indicated that he felt this was not an authentic expression of his "real" self. His experience was that of a splintered world.
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| 21. |
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| 22. |
- Hellzén, Ove, et al.
(författare)
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Unwillingness to be violated : Carers' experiences of caring for a person acting in a disturbing manner. An interview study
- 1999
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 8:6, s. 653-662
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Tidskriftsartikel (refereegranskat)abstract
- Carers working in psychiatric care are sometimes exposed to insane, unpredictable and violent actions. In rare cases a patient appears to be resistant to all forms of pharmacological treatment. · Fifteen carers (4 RNs, 11 ENs) on a psychiatric ward in Sweden were interviewed about their experiences when caring for a person who acted in a disturbing manner. Narrative interviews were conducted and interpreted using a method inspired by Ricoeur. · Four themes were formulated which describe the carers’ uncertainty about the future, their inability to interpret the patient’s disturbing behaviour and their own overall feeling of meaninglessness. · Carers believed that the patient had power and ruled the ward, which led to them feeling they were subjugated victims. Interviews also revealed the carers’ recognition of forbidden feelings and actions and own unknown negative sides. · These results were interpreted and reflected on in the light of an ethical framework in order to achieve a deeper understanding of the text. · This paper shows that an ethical perspective is important when searching for the meaning of caring for patients acting in a disturbing manner. The study raises the question: ‘Is it possible to establish good when evil has dominion?
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| 23. |
- Hoglund, L, et al.
(författare)
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Selective optical doping to predict the performance and reveal the origin of photocurrent peaks in quantum dots-in-a-well infrared photodetectors
- 2009
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Ingår i: INFRARED PHYSICS and TECHNOLOGY. - Exeter : Elsevier BV. - 1350-4495 .- 1879-0275. ; 52:6, s. 272-275
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Tidskriftsartikel (refereegranskat)abstract
- Resonant optical pumping across the band gap was used as artificial doping in InAs/In0.15Ga0.85As/GaAs quantum dots-in-a-well infrared photodetectors. Through efficient filling of the quantum dot energy levels by simultaneous optical pumping into the ground states and the excited states of the quantum dots, the response was increased by a factor of 10. Low temperature photocurrent peaks observed at 120 and 148 meV were identified as intersubband transitions emanating from the quantum dot ground state and the quantum dot excited state, respectively by a selective increase of the electron population in the different quantum dot energy levels.
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| 24. |
- Höglund, Linda, 1974-, et al.
(författare)
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Bias and temperature dependence of the escape processes in quantum dots-in-a-well infrared photodetectors
- 2008
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Ingår i: Applied Physics Letters. - New York : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 93:10, s. 103501-
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Tidskriftsartikel (refereegranskat)abstract
- The performance of quantum dots-in-a-well infrared photodetectors (DWELL IPs) has been studied by means of interband and intersubband photocurrent measurements as well as dark current measurements. Using interband photocurrent measurements, substantial escape of electrons from lower lying states in the DWELL structure at large biases was revealed. Furthermore, a significant variation in the escape probability from energy states in the DWELL structure with applied bias was observed. These facts can explain the strong temperature and bias dependence of both photocurrent and dark currents in DWELL IPs.
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| 25. |
- Höglund, Linda, 1974-, et al.
(författare)
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Bias mediated tuning of the detection wavelength in asymmetrical quantum dots-in-a-well infrared photodetectors
- 2008
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Ingår i: Applied Physics Letters. - New York : AIP Publishing. - 0003-6951 .- 1077-3118. ; 93:20
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Tidskriftsartikel (refereegranskat)abstract
- Bias-mediated tuning of the detection wavelength within the infrared wavelength region is demonstrated for quantum dots-in-a-well and dots-on-a-well infrared photodetectors. By positioning the InAs quantum dot layer asymmetrically in an 8 nm wide In0.15Ga0.85As/GaAs quantum well, a shift in the peak detection wavelength from 8.4 to 10.3 mu m was observed when reversing the polarity of the applied bias. For a dots-on-a-well structure, the peak detection wavelength was tuned from 5.4 to 8 mu m with small changes in the applied bias. These tuning properties could be essential for applications such as modulators and dual-color infrared detection.
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| 26. |
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| 27. |
- Höglund, Linda, 1974-, et al.
(författare)
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Energy level scheme of InAs/InxGa1-xAs/GaAs quantum-dots-in-a-well infrared photodetector structures
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - Woodbury, NY : American Physical Society. - 1098-0121 .- 1550-235X. ; 82:3, s. 035314-
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Tidskriftsartikel (refereegranskat)abstract
- A thorough investigation of quantum-dots-in-a-well structures for infrared photodetector applications has been performed employing different experimental techniques. The electronic structure of self-assembled InAs quantum dots embedded in an In0.15Ga0.85As/GaAs quantum well (QW) was deduced from photoluminescence (PL) and PL excitation (PLE) spectroscopy. From polarization-dependent PL it was revealed that the quantum dots hold two electron energy levels and two heavy-hole levels. Tunnel capacitance spectroscopy confirmed an electron energy level separation of about 50 meV, and additionally, that the conduction-band ground state and excited state of the dots are twofold and fourfold degenerates, respectively. Intersubband photocurrent spectroscopy, combined with simultaneous interband pumping of the dots, revealed a dominant transition at 150 meV (8.5 mu m) between the ground state of the quantum dots and the excited state of the QW. Results from detailed full three-dimensional calculations of the electronic structure, including effects of composition intermixing and interdot interactions, confirm the experimentally unravelled energy level scheme of the dots and well.
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| 28. |
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| 29. |
- Höglund, Linda, 1974-, et al.
(författare)
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Optical pumping as artificial doping in quantum dots-in-a-well infrared photodetectors
- 2009
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Ingår i: Applied Physics Letters. - New York : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:5, s. 053503-
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Tidskriftsartikel (refereegranskat)abstract
- Resonant optical pumping across the band gap was used as artificial doping in InAs/In0.15Ga0.85As/GaAs quantum dots-in-a-well infrared photodetectors. By selectively increasing the electron population in the different quantum dot energy levels, the low temperature photocurrent peaks observed at 120 and 148 meV, could be identified as intersubband transitions emanating from the quantum dot ground state and the quantum dot excited state, respectively. With efficient filling of the quantum dot energy levels through simultaneous optical pumping into the ground states and the excited states of the quantum dots, the response was increased by a factor of 10.
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| 30. |
- Höglund, Linda, 1974-, et al.
(författare)
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Optimising uniformity of InAs/(InGaAs)/GaAs quantum dots grown by metal organic vapor phase epitaxy
- 2006
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Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 252:15, s. 5525-5529
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Tidskriftsartikel (refereegranskat)abstract
- A route towards optimisation of uniformity and density of InAs/(InGaAs)/GaAs quantum dots grown by metal organic vapor phase epitaxy (MOVPE) through successive variations of the growth parameters is reported. It is demonstrated that a key parameter in obtaining a high density of quantum dots is the V/III ratio, a fact which was shown to be valid when either AsH3 (arsine) or tertiary-butyl-arsine (TBA) were used as group V precursors. Once the optimum V/III ratio was found, the size distribution was further improved by adjusting the nominal thickness of deposited InAs material, resulting in an optimum thickness of 1.8 monolayers of InAs in our case. The number of coalesced dots was minimised by adjusting the growth interruption time to approximately 30 s. Further, the uniformity was improved by increasing the growth temperature from 485 °C to 520 °C. By combining these optimised parameters, i.e. a growth temperature of 520 °C, 1.8 monolayers InAs thickness, 30 s growth stop time and TBA as group V precursor, a full-width-half-maximum (FWHM) of the low temperature luminescence band of 40 meV was achieved, indicating a narrow dot size distribution.
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| 31. |
- Höglund, Linda, 1974-, et al.
(författare)
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Origin of photocurrent in lateral quantum dots-in-a-well infrared photodetectors
- 2006
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Ingår i: Applied Physics Letters. - New York : American Institute of Physics. - 0003-6951 .- 1077-3118. ; 88:21
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Tidskriftsartikel (refereegranskat)abstract
- Interband and intersubband transitions of lateral InAs/In0.15Ga0.85As dots-in-a-well quantum dot infrared photodetectors were studied in order to determine the origin of the photocurrent. The main intersubband transition contributing to the photocurrent (PC) was associated with the quantum dot ground state to the quantum well excited state transition. By a comparison between intersubband PC measurements and the energy level scheme of the structure, as deduced from Fourier transform photoluminescence (FTPL) and FTPL excitation spectroscopies, the main transition contributing to the PC was identified.
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| 32. |
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| 33. |
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| 34. |
- Höglund, Linda, 1974-, et al.
(författare)
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Quantum dots-in-a-well infrared photodetectors for long wavelength infrared detection
- 2006
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Ingår i: Proceedings of SPIE. - Bellingham, Wash. : SPIE - International Society for Optical Engineering. - 9780819464996 ; 6401, s. 1-640109
-
Konferensbidrag (refereegranskat)abstract
- We report on a quantum dots-in-a-well infrared photodetector (DWELL QDIP) grown by metal organic vapor phase epitaxy. The DWELL QDIP consisted of ten stacked InAs/In0.5Ga0.85As/GaAs QD layers embedded between n-doped contact layers. The density of the QDs was about 9 × 10 10 cm-2 per QD layer. The energy level structure of the DWELL was revealed by optical measurements of interband transitions, and from a comparison with this energy level scheme the origin of the photocurrent peaks could be identified. The main intersubband transition contributing to the photocurrent was associated with the quantum dot ground state to the quantum well excited state transition. The performance of the DWELL QDIPs was evaluated regarding responsivity and dark current for temperatures between 15 K and 77 K. The photocurrent spectrum was dominated by a LWIR peak, with a peak wavelength at 8.4 μm and a full width at half maximum (FWHM) of 1.1 μm. At an operating temperature of 65 K, the peak responsivity was 30 mA/W at an applied bias of 4 V and the dark current was 1.2×10-5 A/cm2. Wavelength tuning from 8.4 μm to 9.5 μm was demonstrated, by reversing the bias of the detector.
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| 35. |
- Höglund, Linda, et al.
(författare)
-
Studies of photocurrent and dark current in quantum dots-in-a-well infrared photodetectors
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The performance of quantum dots-in-a-well infrared photodetectors (DWELL IPs) has been studied by means of interband and intersubband photocurrent measurements as well as dark current measurements. Using interband photocurrent measurements, substantial escape of electrons from lower lying states in the DWELL structure at large biases was revealed. Furthermore, a significant variation of the escape probability from energy states in the DVELL sturcture with voltage was observed. These facts could be possible explanations to the strong temperature and voltage dependence of hoth photocurrent and dark current in DWELL IPs. In a comparison between DWELL IPs and quantum well infrared photocdetectors (QWIPs), the dark current was shown to be considerably lower in DWELL IPs than in QWIPs, but alos the responsivity was low in comparison to QWIPs.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Höglund, Linda, et al.
(författare)
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Tuning of the detection wavelength in quantum dots-in-a-well infrared photodetectors
- 2008
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Ingår i: Proceedings of SPIE, 6940, Infrared Technology and Applications XXXIV, 694002. - : SPIE. - 9780819471314
-
Konferensbidrag (refereegranskat)abstract
- In this study, bias mediated tuning of the detection wavelength within the infrared wavelength region is demonstrated for quantum dots-in-a-well (DWELL) infrared photodetectors. In DWELL structures, intersubband transitions in the conduction band occur from a discrete state in the quantum dot to a subband inthe quantum well. Compared to "conventional" quantum dot infrared photodetectors, where the transitions take place between different discrete bands in thequantum dots, new possibilities to tune the detection wavelength window are opened up, partly by varying the quantum dot energy levels and partly by adjusting the width and composition of the quantum well. In the DWELL structure used, an asymmetric positioning of the InAs quantum dot layer in a 8 nm wide In0.15Ga0.85As/GaAs QW has been applied which enables tuning of the peak detection wavelength within the long wavelength infrared (LWIR; 8 - 14 gm) region. When the applied bias was reversed, a wavelength shift from 8.5 to 9.5 mu m was observed for the peak position in the spectral response. For another DWELL structure, with a well width of 2 nm, the tuning range of the detector could be shifted from the medium wavelength infrared (MWIR; 3-5 mu m) region to the LWIR region. With small changes in the applied bias, the peak detection wavelength could be shifted from 5.1 to 8 mu m. These tuning properties ofDWELL structures could be essential for applications such as modulators and two-colour infrared detection. © (2008) COPYRIGHT SPIE--The International Society for Optical Engineering.
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| 40. |
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| 41. |
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| 42. |
- Jansson, Lilian, et al.
(författare)
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Interpreting Facial Expressions in Patients in the Terminal Stage of the Alzheimer Disease
- 1993
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Ingår i: Omega. - 0030-2228 .- 1541-3764. ; 26:4, s. 319-334
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Tidskriftsartikel (refereegranskat)abstract
- Videotaped interactions between each of two experienced caregivers and each of four patients in the terminal stage of the Alzheimer disease were interpreted. A hermeneutic approach was used to analyze the videotapes. It was possible to see the patients as capable of having experiences and of communicating them to their caregivers. The analysis made it possible to put together the observed communicative cues into a narrative for each patient. The study may contribute to the improvement of the care of severely demented patients by affecting caregivers' preunderstanding of these patients' experiences and communicative abilities.
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| 43. |
- Korchynska, Solomiia, et al.
(författare)
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Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants
- 2020
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Ingår i: EMBO Journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 39:1
-
Tidskriftsartikel (refereegranskat)abstract
- Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic β cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.
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| 44. |
- Landgraf, Wolfgang, et al.
(författare)
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Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants
- 2022
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 190
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.
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| 45. |
- Le Lay, Aurélie, et al.
(författare)
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Regenerating islet-derived protein 3α : A promising therapy for diabetes. Preliminary data in rodents and in humans
- 2022
-
Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 8:7
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.
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| 46. |
- Myo Min, Kay K, et al.
(författare)
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Desmoglein-2 is important for islet function and β-cell survival
- 2022
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:10
-
Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal that DSG2 is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In a Dsg2 loss-of-function mice (Dsg2lo/lo), we observed a significant reduction in the number of pancreatic islets and islet size, and consequently, there was less total insulin content per islet cluster. Dsg2lo/lo mice also exhibited a reduction in blood vessel barrier integrity, an increased incidence of streptozotocin-induced diabetes, and islets isolated from Dsg2lo/lo mice were more susceptible to cytokine-induced β-cell apoptosis. Following transplantation into diabetic mice, islets isolated from Dsg2lo/lo mice were less effective than their wildtype counterparts at curing diabetes. In vitro assays using the Beta-TC-6 murine β-cell line suggest that DSG2 supports the actin cytoskeleton as well as the release of cytokines and chemokines. Taken together, our study suggests that DSG2 is an under-appreciated regulator of β-cell function in pancreatic islets and that a better understanding of this adhesion molecule may provide new opportunities to combat type 1 diabetes.
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| 47. |
- Norbergh, Karl-Gustaf, et al.
(författare)
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How patients´ with dementia spend their time in a psycho-geriatric unit
- 2001
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 15:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the findings of a work sampling study conducted at an assessment unit for patients with dementia at a university hospital in Nothern Sweden. The aim of the study was to describe the activity of the demented patients´day at apsycho-geriatric unit, and to investigate the correlation between the patients´ characteristics and time provided by nursing staff, in order to increase our knowledge of institutionalized demented patients situation. The sample consited of 24 patients with dementia. The activities of patients were monitored at 10-min interval between 7.00 a.m. and 9.10 p.m. In total, 2024 activities were recorded. The findings showed that being demented and placed in a psycho-geriatric unit is a life in solitude for most of the time. The variationin time patients spent in solitude could partly be explanied by their communication abilities. For patients with dementia, communication is essential for their well-being. It seems important to enhance our knowledge about the reasons, that influence the nursing staffs' perceptions of patients with dementia, to decrease their time in solitude.
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| 48. |
- Normann, Hans Ketil, et al.
(författare)
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People with severe dementia exhibit episodes of lucidity : A population-based study
- 2006
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 15:11, s. 1413-1417
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives. To describe frequency and characteristics of people with severe dementia who according to care providers, exhibit ELs in a population of those with dementia in institutional care.Background. There are reports in the literature concerning episodes when the resident unexpectedly says or acts in a way that surprises the care provider because the resident seems to be much more aware of her/his situation than usual. This is labelled ‘episodes of lucidity’ (ELs).Design. The study is based on data from a point prevalence study from institutions for the older people in northern Sweden in May 2000.Methods. Out of 3804 residents, assessed by key care providers, by means of the Multi-Dimensional Dementia Assessment Scale (MDDAS) with questions about ELs added, 92 residents were found to have severe dementia and difficulties with verbal communication. The key care providers’ competence in assessing severe dementia was not evaluated. An ethics committee approved the study.Results. Fifty-two residents (57%) were assessed as exhibiting ELs. Residents who showed ELs had higher orientation scores and expressed more emotions than residents who did not show ELs. More residents who exhibited ELs took outdoor walks with their care providers exhibited ELs than those who did not (P = 0·001).Conclusions. Every second resident with severe dementia and difficulties with verbal communication showed ELs.Relevance for clinical practice. The fact that every second resident with severe dementia and difficulties with verbal communication showed ELs and that this was noticed especially when care providers took outdoor walks with the residents imply that closer contact between care providers and residents with severe dementia could change the care providers’ expectations and enhance communication between the parties.
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| 49. |
- Pantoni, Leonardo, et al.
(författare)
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Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study : rationale, design and methodology.
- 2005
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 24:1-2, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.
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| 50. |
- Peiris, Heshan, et al.
(författare)
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Discovering human diabetes-risk gene function with genetics and physiological assays
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Developing systems to identify the cell type-specific functions regulated by genes linked to type 2 diabetes (T2D) risk could transform our understanding of the genetic basis of this disease. However, in vivo systems for efficiently discovering T2D risk gene functions relevant to human cells are currently lacking. Here we describe powerful interdisciplinary approaches combining Drosophila genetics and physiology with human islet biology to address this fundamental gap in diabetes research. We identify Drosophila orthologs of T2D-risk genes that regulate insulin output. With human islets, we perform genetic studies and identify cognate human T2D-risk genes that regulate human beta cell function. Loss of BCL11A, a transcriptional regulator, in primary human islet cells leads to enhanced insulin secretion. Gene expression profiling reveals BCL11A-dependent regulation of multiple genes involved in insulin exocytosis. Thus, genetic and physiological systems described here advance the capacity to identify cell-specific T2D risk gene functions.
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