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| 8. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 9. |
- Fredriksson, I, et al.
(författare)
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Risk factors for local recurrence after breast-conserving surgery
- 2003
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:9, s. 1093-1102
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. Method: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. Results: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. Conclusion: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.
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| 11. |
- Fredriksson, Maria
(författare)
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From Customer Satisfaction to Citizen Interaction : a cooperation model for community development based on Total Quality Management
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Current problems with unemployment and the consequences of cut-down in the public sector need appropriate solutions, where private citizens perhaps take on more active roles than today, individually or in groups. The aim with this doctoral thesis is to contribute to one such solution, which is a cooperation model for societal development in local communities, based on Total Quality Management (TQM) and on the participation of many residents. The model is gradually developed with the help of collected experiences and opinions from three stakeholder groups in two different Swedish communities, as well as from general theories and literature. These groups are the quality-project initiators, the community residents and the local politicians. The disposition of the thesis is accordingly. The thesis contains two case studies. The first one concerns the use of TQM as a support of societal development in a local community. The improvement work is conducted within a non-profit organisation built on voluntary engagement. These experiences have then been compared, in the second case study, to the ones in another community where TQM is not used, but where the ambitions are the same. Here the framework for the improvement work is both a non-profit organisation and a for-profit one. The analyses indicate that TQM can be used with success within societal development, even if some of its tools or methodologies are interpreted in new ways, or not used at all. As TQM should be applied with regard to the type of organisation and its purpose, a certain flexibility is both expected and helpful. As far as management is concerned, the leadership needs to be “softer” and more diplomatic when managing unpaid volunteers, as compared to the situation in a commercial enterprise. Another observation is that the societal work is best conducted within groups, defined by situations or activities in life or in the society. An active resident can join a group according to interest. This is a modified version of the “quality circles” inherent to TQM. In a separate, and more theoretical study, the issue of adopting TQM to new sectors in society is discussed. In both the studied societies, there are difficulties to get residents involved or active, which puts into question the mandate with a large community project that aims at improving the quality of life for all residents. There are also difficulties with finding and renewing the leadership, and with communication with, above all, local politicians. Nevertheless, these politicians are in general positive to private initiatives like the ones in the two communities, and consider such projects very important for the future development of rural areas. They think that the experienced weaknesses can be reduced if the improvement work is distinctly defined and organised, if information and communication improve, and if the active residents become more educated about the procedures and limitations of the political governing of the communities. These and other observations of the two communities lead to a model where a cooperation between societal stakeholders develop in three phases; the start-up, the establishment and the continuation of the work. Each phase is discussed separately, and advice is given how to avoid, or meet, various problems that are likely to appear along the way.
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| 14. |
- Nordström, Karl J. V., et al.
(författare)
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Comprehensive comparisons of the current human, mouse, and rat RefSeq, Ensembl, EST, and FANTOM3 datasets : identification of new human genes with specific tissue expression profile
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 348:3, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of functional genetic elements in the genomes is continuously growing and new entries are entered in various databases on a regular basis. We have here merged the genetic elements in RefSeq, Ensembl, FANTOM3, HINV, and NCBI:s ESTdb using the genome assemblies in order to achieve a comprehensive picture of the current status of the identity and gene number in human, mouse, and rat. The number of human protein coding genes has not increased (25,043) while the increased sequencing of mouse transcripts has provided the considerably higher number of protein coding genes (31,578) in mouse. The results indicate large discrepancies between the datasets, as considerable numbers of unique transcripts can be found in each dataset. Despite the high number of ncRNA (38 129 in mouse) there are also almost 20,000 EST clusters in both mouse and humans with more than one EST that do not overlap any transcript suggesting that several new genetic elements are still to be found. We also demonstrated presence of new genes by identifying new human ones that have specific tissue profiles, using RT-PCR on rat tissues.
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| 17. |
- Adamsson, Viola, et al.
(författare)
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Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects : a randomized controlled trial (NORDIET)
- 2011
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Ingår i: Journal of Internal Medicine. - Oxford : Wiley. - 0954-6820 .- 1365-2796. ; 269:2, s. 150-159
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. Design and subjects. In a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects' usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low-density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment-insulin resistance). The ND was rich in high-fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low-fat milk products, but low in salt, added sugars and saturated fats. Results. The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (-16%, P < 0.001), LDL cholesterol (-21%, P < 0.001), high-density lipoprotein (HDL) cholesterol (-5%, P < 0.01), LDL/HDL (-14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (-1%, P < 0.05) in the ND group. The ND reduced insulin (-9%, P = 0.01) and systolic BP by -6.6 +/- 13.2 mmHg (-5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (-4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. Conclusions. A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects.
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| 18. |
- Al-Sabri, Mohamed H., et al.
(författare)
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Statins Induce Locomotion and Muscular Phenotypes in Drosophila melanogaster That Are Reminiscent of Human Myopathy : Evidence for the Role of the Chloride Channel Inhibition in the Muscular Phenotypes
- 2022
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 11:22
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Tidskriftsartikel (refereegranskat)abstract
- The underlying mechanisms for statin-induced myopathy (SIM) are still equivocal. In this study, we employ Drosophila melanogaster to dissect possible underlying mechanisms for SIM. We observe that chronic fluvastatin treatment causes reduced general locomotion activity and climbing ability. In addition, transmission microscopy of dissected skeletal muscles of fluvastatin-treated flies reveals strong myofibrillar damage, including increased sarcomere lengths and Z-line streaming, which are reminiscent of myopathy, along with fragmented mitochondria of larger sizes, most of which are round-like shapes. Furthermore, chronic fluvastatin treatment is associated with impaired lipid metabolism and insulin signalling. Mechanistically, knockdown of the statin-target Hmgcr in the skeletal muscles recapitulates fluvastatin-induced mitochondrial phenotypes and lowered general locomotion activity; however, it was not sufficient to alter sarcomere length or elicit myofibrillar damage compared to controls or fluvastatin treatment. Moreover, we found that fluvastatin treatment was associated with reduced expression of the skeletal muscle chloride channel, C1C-a (Drosophila homolog of CLCN1), while selective knockdown of skeletal muscle C1C-a also recapitulated fluvastatin-induced myofibril damage and increased sarcomere lengths. Surprisingly, exercising fluvastatin-treated flies restored C1C-a expression and normalized sarcomere lengths, suggesting that fluvastatin-induced myofibrillar phenotypes could be linked to lowered C1C-a expression. Taken together, these results may indicate the potential role of C1C-a inhibition in statinassociated muscular phenotypes. This study underlines the importance of Drosophila melanogaster as a powerful model system for elucidating the locomotion and muscular phenotypes, promoting a better understanding of the molecular mechanisms underlying SIM.
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| 19. |
- Andrae, Johanna, et al.
(författare)
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A role for PDGF-C/PDGFR alpha signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex
- 2016
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 5:4, s. 461-474
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFR alpha. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFR alpha ligands might obscure additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc(-/-) and Pdgfra(GFP/+). These mice display a range of severe phenotypes including spina bifida, lung emphysema, abnormal meninges and neuronal over-migration in the cerebral cortex. We focused our analysis on the central nervous system (CNS), where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane. We also present expression data on Pdgfa, Pdgfc and Pdgfra in the cerebral cortex and microarray data on cerebral meninges.
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| 20. |
- Anton, Nicholas, et al.
(författare)
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Exhaust volume dependency of turbocharger turbine design for a heavy duty otto cycle engine
- 2017
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Ingår i: Proceedings of the ASME Turbo Expo. - : ASME Press. - 9780791850800
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Konferensbidrag (refereegranskat)abstract
- This study is considering turbocharger turbine performance at "on-engine" conditions with respect to turbine design variables and exhaust manifold volume. The highly unsteady nature of the internal combustion engine will result in a very wide range of turbine operation, far from steady flow conditions. As most turbomachinery design work is conducted at steady state, the influence of the chosen turbine design variables on the crank-angle-resolved turbine performance will be of prime interest. In order to achieve high turbocharger efficiency with the greatest benefits for the engine, the turbine will need high efficiency at the energetic exhaust pressure pulse peak. The starting point for this paper is a target full load power curve for a heavy duty Otto-cycle engine, which will dictate an initial compressor and turbine match. Three radial turbine designs are investigated, differing with respect to efficiency characteristics, using a common compressor stage. The influence of the chosen turbine design variables considering a main contributor to unsteadiness, exhaust manifold volume, is evaluated using 1D engine simulation software. A discussion is held in conjunction with this regarding the efficiency potential of each turbine design and limitations of turbine types.
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- Baumgart, Mona, et al.
(författare)
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Design of buried charged networks in artificial proteins
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Soluble proteins are universally packed with a hydrophobic core and a polar surface that drive the protein folding process. Yet charged networks within the central protein core are often indispensable for the biological function. Here, we show that natural buried ion-pairs are stabilised by amphiphilic residues that electrostatically shield the charged motif from its surroundings to gain structural stability. To explore this effect, we build artificial proteins with buried ion-pairs by combining directed computational design and biophysical experiments. Our findings illustrate how perturbation in charged networks can introduce structural rearrangements to compensate for desolvation effects. We validate the physical principles by resolving high-resolution atomic structures of the artificial proteins that are resistant towards unfolding at extreme temperatures and harsh chemical conditions. Our findings provide a molecular understanding of functional charged networks and how point mutations may alter the protein's conformational landscape.
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| 24. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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Identification of novel splice variants of Adhesion G protein-coupled receptors
- 2007
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 387:1-2, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- Alternative splicing is an important mechanism to generate proteome diversity in higher eukaryotic organisms. We searched for splice variants of the human Adhesion family of G protein-coupled receptors (GPCRs) using mRNA sequences and expressed sequence tags. The results presented here describe 53 human splice variants among the 33 Adhesion GPCRs. Many of these variants appear to be coding for “functional” proteins (29) while the others are seemingly “non-functional” (24). Novel functional splice variants were found for: CD97, CELR3, EMR2, EMR3, GPR56, GPR110, GPR112–GPR114, GPR116, GPR123–GPR126, GPR133, HE6, and LEC1–LEC3. Splice variants for GPR116, GPR125, GPR126, and HE6 were found conserved in other species. Several of the functional splice variants lack one or more of the functional domains that are found in the N-termini of these receptors. These functional domains are likely to affect ligand binding or interaction with other proteins and these novel splice variants may have important roles for the specificity of interactions between these receptors and extracellular molecules. Another type of splice variants found here lacks a GPCR proteolytic site (GPS). The GPS domain has been shown to be essential for the proteolytic cleavage of the receptors N-termini and for cellular surface expression. We suggest that these alternative splice variants may be crucial for the function of the receptors while the seemingly non-functional splice variants may be a part of a regulative mechanism.
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| 25. |
- Bonilla Hernández, Ana Esther, et al.
(författare)
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Process sustainability evaluation for manufacturing of a component with the 6R application
- 2019
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Ingår i: Procedia Manufacturing. - : Elsevier BV. - 2351-9789. ; 33, s. 546-553
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Tidskriftsartikel (refereegranskat)abstract
- Sustainability in manufacturing can be evaluated at product, process and system levels. The 6R methodology for sustainability enhancement in manufacturing processes includes: reduced use of materials, energy, water and other resources; reusing of products/components; recovery and recycling of materials/components; remanufacturing of products; and redesigning of products to utilize recovered materials/resources. Although manufacturing processes can be evaluated by their productivity, quality and cost, process sustainability assessment makes it a complete evaluation. This paper presents a 6R-based evaluation method for sustainable manufacturing in terms of specific metrics within six major metrics clusters: environmental impact, energy consumption, waste management, cost, resource utilization and society/personnel health/operational safety. Manufacturing processes such as casting, welding, turning, milling, drilling, grinding, etc., can be evaluated using this methodology. A case study for machining processes is presented as an example based on the proposed metrics. © 2019 The Authors. Published by Elsevier B.V.
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| 30. |
- Egecioglu, Emil, 1977, et al.
(författare)
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The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:8, s. 1259-1270
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Tidskriftsartikel (refereegranskat)abstract
- Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.
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| 33. |
- Feltmann, K., et al.
(författare)
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The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats
- 2016
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 21:2, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- We recently established that the monoamine stabilizer (-)-OSU6162 (OSU6162) decreased voluntary alcohol-mediated behaviors, including alcohol intake and cue/priming-induced reinstatement, in long-term drinking rats, while blunting alcohol-induced dopamine output in the nucleus accumbens (NAc) of alcohol-naive rats. Therefore, we hypothesized that OSU6162 attenuates alcohol-mediated behaviors by blunting alcohol's rewarding effects. Here, we evaluated the effects of long-term drinking and OSU6162 treatment (30mg/kg, sc) on basal and alcohol-induced (2.5g/kg, ip) NAc dopamine outputs in Wistar rats after 10months of intermittent access to 20% alcohol. The results showed that basal and alcohol-induced NAc dopamine outputs were significantly lower in long-term drinking rats, compared with alcohol-naive rats. In the long-term drinking rats, OSU6162 slowly increased and maintained the dopamine output significantly elevated compared with baseline for at least 4hours. Furthermore, OSU6162 pre-treatment did not blunt the alcohol-induced output in the long-term drinking rats, a finding that contrasted with our previous results in alcohol-naive rats. Finally, OSU6162 did not induce conditioned place preference (CPP) in either long-term drinking or alcohol-naive rats, indicating that OSU6162 has no reinforcing properties. To verify that the CPP results were not due to memory acquisition impairment, we demonstrated that OSU6162 did not affect novel object recognition. In conclusion, these results indicate that OSU6162 attenuates alcohol-mediated behaviors by counteracting NAc dopamine deficits in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with OSU6162's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in alcohol-dependent patients.
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| 37. |
- Fredriksson, A, et al.
(författare)
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Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice
- 1999
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Ingår i: TOXICOLOGY AND APPLIED PHARMACOLOGY. - : ACADEMIC PRESS INC. - 0041-008X. ; 159:1, s. 25-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Excess iron in the brain has been implicated in the pathogenesis of several human neurodegenerative disorders, i.e., Parkinson's and Alzheimer's disease. The neonatal period is critical for the establishment of normal iron content in the adult brain. In t
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| 40. |
- Fredriksson, I, et al.
(författare)
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Consequences of axillary recurrence after conservative breast surgery
- 2002
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 89:7, s. 902-908
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. Methods: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. Results: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. Conclusion: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.
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| 44. |
- Fredriksson, I, et al.
(författare)
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Local recurrence in the breast after conservative surgery - A study of prognosis and prognostic factors in 391 women
- 2002
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 38:14, s. 1860-1870
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI). ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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