| 1. |
- Borgegard, Tomas, et al.
(författare)
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Alzheimers Disease: Presenilin 2-Sparing gamma-Secretase Inhibition Is a Tolerable A beta Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase inhibition represents a major therapeutic strategy for lowering amyloid beta (A beta) peptide production in Alzheimers disease (AD). Progress toward clinical use of gamma-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The gamma-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between A beta production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1(PS1) over PS2 subclass of gamma-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain A beta levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious gamma-secretase targeting strategy for AD.
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| 2. |
- Borgegård, Tomas, et al.
(författare)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
-
Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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| 3. |
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| 4. |
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| 5. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 6. |
- Aminoff, Hedvig, et al.
(författare)
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Telemedicine for Remote Surgical Guidance in Endoscopic Retrograde Cholangiopancreatography : Mixed Methods Study of Practitioner Attitudes
- 2021
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Ingår i: JMIR Formative Research. - : JMIR Publications. - 2561-326X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Telemedicine innovations are rarely adopted into routine health care, the reasons for which are not well understood. Teleguidance, a promising service for remote surgical guidance during endoscopic retrograde cholangiopancreatography (ERCP) was due to be scaled up, but there were concerns that user attitudes might influence adoption.OBJECTIVE: Our objective was to gain a deeper understanding of ERCP practitioners' attitudes toward teleguidance. These findings could inform the implementation process and future evaluations.METHODS: We conducted semistructured interviews with ERCP staff about challenges during work and beliefs about teleguidance. Theoretical constructs from the technology acceptance model (TAM) guided the thematic analysis. Our findings became input to a 16-item questionnaire, investigating surgeons' beliefs about teleguidance's contribution to performance and factors that might interact with implementation.RESULTS: Results from 20 interviews with ERCP staff from 5 hospitals were used to adapt a TAM questionnaire, exchanging the standard "Ease of Use" items for "Compatibility and Implementation Climate." In total, 23 ERCP specialists from 15 ERCP clinics responded to the questionnaire: 9 novices (<500 ERCP procedures) and 14 experts (>500 ERCP procedures). The average agreement ratings for usefulness items were 64% (~9/14) among experts and 75% (~7/9) among novices. The average agreement ratings for compatibility items were somewhat lower (experts 64% [~9/14], novices 69% [~6/9]). The averages have been calculated from the sum of several items and therefore, they only approximate the actual values. While 11 of the 14 experts (79%) and 8 of the 9 novices (89%) agreed that teleguidance could improve overall quality and patient safety during ERCP procedures, only 8 of the 14 experts (57%) and 6 of the 9 novices (67%) agreed that teleguidance would not create new patient safety risks. Only 5 of the 14 experts (36%) and 3 of the 9 novices (33%) were convinced that video and image transmission would function well. Similarly, only 6 of the 14 experts (43%) and 6 of the 9 novices (67%) agreed that administration would work smoothly. There were no statistically significant differences between the experts and novices on any of the 16 items (P<.05).CONCLUSIONS: Both novices and experts in ERCP procedures had concerns that teleguidance might disrupt existing work practices. However, novices were generally more positive toward teleguidance than experts, especially with regard to the possibility of developing technical skills and work practices. While newly trained specialists were the main target for teleguidance, the experts were also intended users. As experts are more likely to be key decision makers, their attitudes may have a greater relative impact on adoption. We present suggestions to address these concerns. We conclude that using the TAM as a conceptual framework can support user-centered inquiry into telemedicine design and implementation by connecting qualitative findings to well-known analytical themes.
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| 7. |
- Andersson, Urban, 1965, et al.
(författare)
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ORCiD @ Chalmers: Membership and implementation
- 2014
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Ingår i: Open Repositories 2014, June 9-13, Helsinki, Finland.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Chalmers University became an institutional member of the ORCID community in June 2013. The membership, as well as the local ORCID services and support, is coordinated and maintained by the university library.Since then we have completed the first phase of the implementation of ORCID id:s at the university - including a pilot project, in which we worked closely together with one of the research departments, and the development of a new easy-to-use web service for the creation of ORCID id:s and for connecting these – and existing id:s - to the university infrastructure, by the use of API:s provided by ORCID and corresponding systems.This service was launched in January 2014 and can be found at orcid.chalmers.se.The proposed poster will demonstrate the current status of our project and what has been done up until now - including workflows, infrastructure integration, technical implementation and, of course, detailed screenshots to illustrate the different parts of the process.It will also include our key experiences so far, as well as to try and provide a quick look into the future and what our next steps might be.
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| 8. |
- Backe, Susanne, et al.
(författare)
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Markanvändningsbetingade vegetationsförändringar inom öppen myr 1987-2000 i Norrbottens län- Satellitbaserad övervakning
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Miljöövervakning av våtmarker bedrivs inom Naturvårdsverkets programområde våtmark med syfte att långsiktigt följa utvecklingen av våtmarkernas tillstånd vad gäller hydrologiskorördhet och biologisk mångfald. För ett av delprogrammen används en satellitbaserad metodik för att upptäcka markanvändningsbetingade vegetationsförändringar i öppna myrar. Metoden baseras på antagandet att spektralt och vegetationsmässigt homogena myrtyper uppträder likartat med avseende på normal variation i fenologi och väder. Detta innebär att om grupper av homogena myrtyper avgränsas vid tidpunkt 1 så kan spektralt avvikande myrar, dvs förändrade myrar, sökas genom riktad förändringsanalys inom grupperna vid tidpunkt 2. Förändringsriktningen som analyserats är ökad biomassa/igenväxning. Förändringarna redovisas i två klasser; säker och potentiell. Analysen kommer att genomföras i hela landet nedanför fjällen från norr till söder med ett omdrev på tio år.Under 2008 utfördes denna förändringsanalys i Norrbottens län. Satellitscenerna som har använts är för tidpunkt 1 från 1984, 1987 samt 1990 och för tidpunkt 2 från 2000. Analysen har resulterat i en mängd ytor inom öppen myr där indikationer på förändring finns. De förändrade ytorna omfattar ca 16 800 ha, vilket motsvarar 1,22 % av arealen öppen myr i undersökningsområdet, dvs hela Norrbottens län med undantag av fjällenVid en utvärdering av resultatet från förändringsanalysen ingick totalt 300 ytor varav 250 förändrade ytor och 50 referensytor. Referensytorna slumpades ut inom den oförändrade delen av den öppna myrmasken. Utvärderingen utfördes mha flygbilder och fältbesök för att verifera förändringar. Utvärderingen visade att säkerheten i förändringsanalysen var mellan 48-91 %. I 48 % av ytorna kunde förändring verifieras. I ytterligare 43 % av fallen var det svårt att bedöma om en förändring skett, men möjlighet fanns att biomassa kan ha ökat under aktuell tidsperiod, dvs säkerheten i analysen kan vara upp till 91%. Förändringsytorna skiljde sig från referensytorna genom att de i högre grad låg i anslutning till vattendrag, sjöar och dråg samt hade fler ingrepp i omgivningen. Vanligast förekommande ingrepp inom 100 m från de förändrade ytorna var dikningar, ungskogar och upphörd myrslåtter. I de östra delarna kunde förändringarna i högre grad verifieras jämfört med i de västra delarna. I väster fanns fler svårbedömda fall. Med andra ord kan man säga att förändringsanalysen har en högre säkerhet och i högre grad kan kopplas till markanvändning i de östra jämfört med de västra delarna. En möjlig orsak till denna skillnad kan vara att fenologiska effekter påverkar analysresultatet i mer höglänta områden med kortare vegetationsperiod.Markanvändning i anslutning till de förändrade myrarna har analyserats med hjälp av flygbildstolkning av de förändrade ytornas tillrinningsområde. Flygbilderna som användes var från tre olika tidsperioder : 1960-, 1980- och 2000-tal. Markanvändningen i anslutning till de förändrade ytorna hade ökat i högre grad jämfört med referensytor. Ökningen har framförallt skett under perioden 1980 till 2000. Diken för skogsbruk stod för den största delen av ökningen.Kring ytor med säker förändringsindikation fanns en större andel skogsdiken jämfört med ytor som hade potentiell förändringsindikation. Det fanns fler rester av lador och hässjor sedan myrslåtterepoken kring de förändrade ytorna jämfört med referensytorna. Markanvändningsanalysen gav oss ytterligare en bekräftelse på att resultatet från förändringsanalysen fångat upp ytor där snabba förändringar i form av igenväxning skett pga ingrepp.Ett förslag på indikator för att följa miljökvalitetsmålet för Myllrande våtmarker har tagits fram baserat på resultatet från förändringsanalysen. Förslaget är att man använder måttet andel förändrad öppen myr av den totala arealen öppen myr som indikator på snabba förändringar.Vi föreslår att indikatorn används dels på länsnivå och dels på kommunnivå.
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| 9. |
- Berg, Christoffer, 1986-
(författare)
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Public Planning, Neoliberal Hybridity and Local Activism in Sundbyberg : Epochal Reconfiguration of Urban Development in Greater Stockholm
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Which urban policy responses are deployed when a small social democratic municipality in a greater city region aims to be competitive for private investments in housing and the built environment? Which new institutional development arrangements are implemented for this purpose, in the wake of a decades-long hegemonic position of the municipal public housing company? This thesis draws on a qualitative case study design to approach such questions, and investigates recent urban development in Sundbybergs stad in Greater Stockholm to answer them. Theoretically, the thesis draws on a theory of neoliberal localization in combination with Henri Lefebvre’s theory of the social production of space. The thesis is thereby able to explain how the municipality consolidated political power, institutional infrastructures, and administrative capacities with a view to introducing a market-based paradigm of urban development. It argues that this paradigm became characterized by a neoliberal hybridity. It supports this argument by analyzing three major development projects targeting three areas with very different sociospatial characteristics. The thesis thereby demonstrates how market-based developments integrated a number of regulatory features and public planning interventions in accordance with certain objectives, concerns, and conditions. E.g., it reveals how the development of a 1970s Million Homes Programme area, Hallonbergen, relied both on an extended sale of public assets to support private developers’ investments with the objective of comprehensively transforming the area, and on extraordinary measures for ‘social sustainability’. It also reveals how the development of the original municipal town, Central Sundbyberg, was arranged in a municipal development company. This established a business-like format for political control and external expertise, while undermining public planning and clouding democratic accountability. This point is further emphasized by analyzing local inhabitants’ methods for contesting certain development features and land use proposals in this project, enforcing a re-politicization of a largely depoliticized development project. Ultimately, the thesis contributes new knowledge on the variegating forms of neoliberal urbanism through an atypical case of a subordinate city region municipality that historically has been characterized by social democracy, a large public rental housing structure, a public housing company with control of spatial planning, and working-class populations and industries.
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| 10. |
- Bäckström, Josefin, Med dr, 1977-, et al.
(författare)
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Assessment and Evaluation Methods in APN Education
- 2024
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Ingår i: Navigating the Future. Advanced Practice Nursing Educational Tools for Success. - : Nordic/Baltic Advanced Practice Nursing Educators NORDPLUS network. ; , s. 41-53
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Assessing nursing skills, whether in the first term of a bachelor’s programme or the final term of an APN programme, is, from our experience, a topic frequently discussed among colleagues. This collaborative discussion occurs irrespective of whether the assessment or evaluation targets more solitary theoretical course activities or theoretical knowledge manifested as clinical skills. In all courses – and in broader perspective educational programmes – it is pivotal that teachers and educators, together with students, ensure that learning activities allow students to achieve the expected learning outcomes. All components, from the curriculum to course content and activities, intended outcomes, and evaluation and assessment methods and tools, should be aligned.Since these are fundamentally based on theoretical knowledge, it is seldom meaningful or purposeful to differentiate between theoretical and clinical nursing skills in clinical skill evaluation and assessments. Hence, assessing clinical skills will also always include theoretical knowledge and reasoning.This chapter will comprehensively summarise formative and summative evaluation and assessment tools and guidelines relevant to APN education, highlighting best practices for evaluating educational outcomes and competencies which are essential in Advanced Practice Nursing. Numerous methods and tools in this chapter may apply to education at both bachelor’s and master’s level and to other healthcare professions. In this chapter, we emphasise that assessment and evaluation are closely related concepts, where formative methods are related to an evaluation approach, and summative methods are related to an assessment approach. By the end of this chapter, educators and students will feel well-informed and prepared to implement these tools and guidelines in their educational practices.
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