1. |
- Ali, Imran, et al.
(författare)
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Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.
- 2012
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 127:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.
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2. |
- Andersson, Lenastina, et al.
(författare)
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Mälsåker Revisited: Museum och Iscensättning. : Kungl Konsthögskolan. Restaureringskonst 2015-2016
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- Rapporten redovisar arbeten från kursen Restaureringskonst på Konsthögskolan som under läsåret 2015-2016 har arbetat med tema Museum och Iscensättning. Hur kulturmiljöer påverkas när de blir museum, hur man restaurerar för museum, hur man bevarar och utvecklar en plats för kunskapsutbyte, bildning och upplevelser. Mälsåkers slott, utanför Mariefred, förvaltat av Statens Fastighetsverk, var studieobjekt för 20 studenter, (yrkesverksamma arkitekter, antikvarier, ingenjörer, konservatorer m fl) där utbildningens olika studiemoment som uppmätning, inventering, dokumentation har tillämpats. Fältarbetet har följts av studier i historik, kulturhistorisk värdering och analyser som gett visioner och gestaltningsförslag på ny verksamhet i slottet. Rapporten presenterar förslagen, med text, skisser, foton och ritningar. Fyra olika typer av museum med varierande grad av åtgärder, förändringar och utveckling av slottet. Restaureringsexperiment redovisas utifrån traditionella och digitala dokumentationsmetoder. Dessutom finns arbeten om barockens ljus, bladguld, brandskydd, pod-radio, kraftstation, engelska parken, dekorationsmålade tak, Gustavianum, Julius Kronbergs ateljé och barockträdgård m m. Förslagen visar att det är möjligt att transformera Mälsåkers barockslott till ett museum av idag med bibehållen historik och synliga tidslager.
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3. |
- Berglund, Annika, et al.
(författare)
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Face Arm Speech Time Test use in the prehospital setting, better in the ambulance than in the emergency medical communication center
- 2014
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Ingår i: Cerebrovascular Diseases. - Basel, Switzerland : S. Karger. - 1015-9770 .- 1421-9786. ; 37:3, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prehospital identification of acute stroke increases the possibility of early treatment and good outcome. To increase identification of stroke, the Face Arm Speech Time (FAST) test was introduced in the Emergency Medical Communication Center (EMCC). This substudy aims to evaluate the implementation of the FAST test in the EMCC and the ambulance service.METHODS: The study was conducted in the region of Stockholm, Sweden during 6 months. The study population consisted of all calls to the EMCC concerning patients presenting at least one FAST symptom or a history/finding making the EMCC or ambulance personnel to suspect stroke within 6 h. Positive FAST was compared to diagnosis at discharge. Positive predictive values (PPV) for a stroke diagnosis at discharge were calculated.RESULTS: In all, 900 patients with a median age of 71 years were enrolled, 667 (74%) by the EMCC and 233 (26%) by the ambulances. At discharge, 472 patients (52%) were diagnosed with stroke/transient ischemic attack (TIA), 337 identified by the EMCC (71%) and 135 (29%) by the ambulances. The PPV for a discharge diagnosis of stroke/TIA was 51% (CI 47-54%) in EMCC-enrolled and 58% (CI 52-64%) in ambulance-enrolled patients. With a positive FAST the PPV of a correct stroke/TIA diagnosis increased to 56% (CI 52-61%) and 73% (CI 66-80%) in EMCC- and ambulance-enrolled patients, respectively. Positive FAST from EMCC was also found in 44% of patients with a nonstroke diagnosis at discharge. A stroke/TIA diagnosis at discharge but negative FAST was found in 58 and 27 patients enrolled by the EMCC and ambulances, respectively.CONCLUSIONS: The PPV of FAST is higher when used on the scene by ambulance than by EMCC. FAST may be a useful prehospital tool to identify stroke/TIA but has limitations as the test can be negative in true strokes, can be positive in nonstrokes, and FAST symptoms may be present but not identified in the emergency call. For the prehospital care situation better identification tools are needed.
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4. |
- Berglund, Annika, et al.
(författare)
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Factors facilitating or hampering nurses identification of stroke in emergency calls
- 2015
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 71:11, s. 2609-2621
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Tidskriftsartikel (refereegranskat)abstract
- Aims. To explore the factors that facilitate or hamper identification of stroke in emergency calls concerning patients with stroke who have fallen or been in a lying position.Background. Early identification of stroke in emergency calls is vital but can be complicated as the patients may be unable to express themselves and the callers generally are bystanders. In a previous study, we found presentation of fall or the patient being in a lying position to be the major problem in 66% of emergency calls concerning, but not dispatched as acute stroke.Design. A qualitative study using interpretive phenomenology.Methods. Analysis of transcribed emergency calls concerning 29 patients with stroke diagnoses at hospital discharge, in 2011 and presented with fall/lying position.Findings. Patients' ability to express themselves, callers' knowledge of the patient and of stroke, first call-takers' and nurses' authority, nurses' coaching and nurses' expertise skills facilitated or hindered the identification of stroke. Certain aspects are adjustable, but some are determined by the situation or on callers' and patients' abilities and thus difficult to change. Nurses' expertise skills were the only theme found to have a decisive effect of the identification of stroke on its own.Conclusion. To increase identification of stroke in emergency calls concerning stroke, the first call-takers' and nurses' action, competence and awareness of obstacles are crucial and if strengthened would likely increase the identification of stroke in emergency calls. In complicated cases, nurses' expertise skills seem essential for identification of stroke.
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5. |
- Berglund, Annika, et al.
(författare)
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Higher prehospital priority level of stroke improves thrombolysis frequency and time to stroke unit : the Hyper Acute STroke Alarm (HASTA) study
- 2012
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Ingår i: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 43:10, s. 2666-2670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences.METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel.RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention.CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.
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6. |
- Berglund, Annika, et al.
(författare)
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Identification of stroke during the emergency call : a descriptive study of callers' presentation of stroke
- 2015
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Ingår i: BMJ Open. - London, UK : BMJ Publishing Group Ltd. - 2044-6055. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate symptoms presented by the caller during emergency calls regarding stroke, and to assess if symptoms in the Face-Arm-Speech-Time Test (FAST) are related to identification of stroke.SETTING: Emergency calls to the Emergency Medical Communication Center (EMCC) concerning patients discharged with stroke diagnosis in a large teaching hospital in Stockholm, Sweden, in January-June 2011.PARTICIPANTS: The emergency calls of 179 patients who arrived at hospital by ambulance, and who were discharged with a stroke diagnosis and consented to participate were included in the study.OUTCOME MEASURES: Frequencies of stroke symptoms presented and a comparison of symptoms presented in calls with dispatch code stroke or other dispatch code.RESULTS: Of the 179 emergency calls analysed, 64% were dispatched as 'Stroke'. FAST symptoms, that is, facial or arm weakness or speech disturbances, were presented in 64% of the calls and were spontaneously revealed in 90%. Speech disturbance was the most common problem (54%) in all calls, followed by fall/lying position (38%) and altered mental status (27%). For patients with dispatch codes other than stroke, the dominating problem presented was a fall or being in a lying position (66%), followed by speech disturbance (31%) and altered mental status (25%). Stroke-specific symptoms were more common in patients dispatched as stroke. FAST symptoms were reported in 80% of patients dispatched as stroke compared with 35% in those dispatched as something else.CONCLUSIONS: This study implicates that fall/lying position and altered mental status could be considered as possible symptoms of stroke during an emergency call. Checking for FAST symptoms in these patients might uncover stroke symptoms. Future studies are needed to evaluate if actively asking for FAST symptoms in emergency calls presenting falls or a lying position can improve the identification of stroke.TRIAL REGISTRATION NUMBER: Stroke2010/703-31/2.
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7. |
- Berglund, Annika, et al.
(författare)
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Knästroppar för barn med cerebral pares : tryckmätning
- 1999
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Ingår i: Nordisk fysioterapi. - 1402-3024. ; 3:2, s. 65-71
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Kneeblocks are used to create a symmetric sitting position for individuals with different physical disabilities. The aim of this paper was to examine the impact of kneeblocks in children with cerebral palsy. Six children aged 4-13 years (mean 9 years) participated in the study. Pressure applied to the children's legs was measured with a computer aided system with waterfilled plastic bags and a pressure transducer with 2 Hz registration continuously during 3 minutes. The registrations were made in four difference sitting positions - horizontal sea and 5 degrees forward inclined, seat with and without a hipbelt, while the children performed different standardised tasks at a table. This was documented by videofile and photographs. The results were presented for the different sitting positions and tasks. The means pressure varied from 0.5 kPa in the sitting position with horizontal seat with a hipbelt to 5.2kPa in the position with 5 degrees forward inclined without a hipbelt. Occasionally pressure up to 24.5 kPa was measured. The kneeblocks did constantly exert pressure on the children's legs, but the pressure varied. If kneeblocks are used it should be in combination with a hipbelt, to minmise the pressure applied to the children's legs.
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8. |
- Berglund, Annika
(författare)
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Prehospital identification and priority of acute stroke
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment of acute ischemic stroke is time critical and early initiated reperfusion treatment increases the chances of good recovery. However, in 2007, only 3% of ischemic stroke patients were treated with thrombolysis in Sweden. Patients’ late arrival to hospital was considered to be one of the reasons for the low treatment rate. The aim of the first study was to evaluate if delay to treatment could be decreased with high priority dispatch of ambulance and thus increase the number of patients eligible for thrombolytic treatment. As high priority of suspected stroke patients is dependent on identification of stroke, the following studies aimed to evaluate identification of stroke. Study I: Patients (n 942) with suspected stroke within 6 h, aged 18-85 were randomized from EMCC or ambulance to intervention, Priority 1 alarm or control, Priority 2. The intervention group randomized from EMCC arrived to hospital 13 minutes (p <0.001) earlier, and 26 minutes (p <0.001) earlier to stroke unit compared to the control group. Furthermore, twice as many patients in the intervention group (35%, p <0.001) were treated with thrombolysis compared to the patients in the control group (17%). The conclusion of the study was that higher priority, both pre- and in-hospital is favorable for patients with acute stroke. Study II was a descriptive study of the use of the Face-Arm-Speech-Time test (FAST) in identification of stroke by the EMCC and the ambulance in the patients included in Study I. In all, 52% of the patients were correctly identified as stroke/TIA. The EMCC included 71% of the patients with stroke/TIA diagnosis and the ambulance included another 29%. At least one FAST symptom was positive in 64% of the included patients. The positive predictive value, PPV, for FAST was 56% in the EMCC included patients and 74% in the ambulance included patients. The conclusion was that FAST is not enough to support identification of stroke in emergency calls. The study demonstrated that more information of how stroke is expressed in emergency calls concerning stroke is needed to improve identification. Study III was a descriptive study of symptoms expressed by the caller in emergency calls concerning stroke of the 179 emergency calls included 64% were dispatched as stroke. Speech disturbance (54%), fall or lying position (38%) and altered mental status (27%) were the most common symptoms in calls. FAST symptoms were presented in 64% of the calls and were more commonly presented in calls dispatched as stroke. The FAST symptoms were presented spontaneously by the caller in 90 %. Fall or the patient being in a lying position (66%) was the most dominating problem presented in the stroke calls dispatched as non-stroke. These result show that FAST is rarely asked for and that the calls dispatched as non-stroke often were presented as a fall or the patient being in a lying position. Questions about FAST symptoms in emergency calls with fall/lying position or altered mental status presented may improve identification of stroke. Study IV was a qualitative study of obstacles and facilitators in communication and interaction of the participants in emergency calls concerning stroke using interpretive phenomenology. Of the 68 emergency calls from Study III where fall/lying position were presented, 29 calls were analyzed. The dispatch codes were blinded in the first step of analysis, 13 calls were dispatched as stroke and 16 as non-stroke. The nurses’ expertise skills were the identified aspect that could be decisive in identification of stroke. Other important findings were aspects of the first call-taker and nurse that can be influenced to improve identification, such as authority, competence and coaching strategies. The result indicated need of education and training to improve identification of stroke and to support the process of developing expertise skills.
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9. |
- Berglund, Annika, et al.
(författare)
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Stroke
- 2016. - 2
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Ingår i: Prehospital akutsjukvård. - Stockholm : Liber. - 9789147114740 ; , s. 373-379
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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12. |
- Berglund, Karin, 1967-, et al.
(författare)
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Engaged Sisters : studying the entrepreneurship and innovation support system from ‘within’
- 2013
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Konferensbidrag (refereegranskat)abstract
- Entrepreneurship and innovation support has grown into large institutions in a society that cherishes an enterprising culture. Individuals are encouraged to be entrepreneurial and innovative in general, and to start up their own companies in particular. To support individuals in their business creation processes, policy stresses the need of providing with measures. Together these measures comprise a support system, directed towards supporting new and established entrepreneurs. It has however been recognized that the entrepreneurship and innovation public support system is highly gendered, favoring men and male businesses, whilst programs targeting women put the onus on individual women to start and grow businesses. As well it has been recognized that the policy support system tends to exclude ‘othered’ groups rather than including them in enterprising activities. The subtext of entrepreneurship support points to how some people “are” entrepreneurs, whilst others need support in order to become more entrepreneurial. Hence, there is a need to change the support system of entrepreneurship and innovation since it tends to disempower rather than to empower ‘othered’ groups in society.“Sisters in Business” make up an organization of wo/men entrepreneurs who have joined forces to address this need. Their vision is that entrepreneurship should reflect the society at large. During the last year they have therefore taken several initiatives to make this happen and is today one of the support organizations in a medium sized Swedish town. In this paper three Sisters are working together with a researcher within this area. Together we have formed a group of “engaged sisters´”. In our dialogue the dichotomy between ‘practice’ and ‘theory’ have temporarily dissolved in favor of creating narratives, from episodes, experiences and the everyday life of sister´s, to illustrate how the support system works from ‘within’. This led us to questioning whether the ‘support system’ really is a support system, or something else? Furthermore, this insight made it apparent that there exists ‘other’ support system, tough concealed and silenced. Finally, suggestions are proposed for how ‘practitioners’ can work together with ‘academics’ to change the rules of the game.
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13. |
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14. |
- Berglund, Karin, et al.
(författare)
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Entrepreneurship and the Enterprising Self Creating alternatives through entrepreneurship education?
- 2015
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Konferensbidrag (refereegranskat)abstract
- The entrepreneurial logic has spread via an abundance of organisations and variouspeoples that embrace the promise of prosperity it indoctrinates. Apart from thegeneration of new companies and market places this indoctrination also entails aflexible invention of enterprising subjectivities. Recently, we have seen adiversification of the contexts in which enterprising subjectivities are invited toundergird entrepreneurship. For example in the context of social entrepreneurship(Dey, 2014) and ecopreneurship (Skoglund, forthcoming). How we are invited tohappily join in and contribute to this entrepreneurship discourse, even as criticalscholars, needs to be seriously considered as the variety of enterprising selvesadvances. As researchers teaching in entrepreneurship we believe that it is not enoughto contemplate upon and write papers about, but also find new approaches to,entrepreneurship studies and teaching thereof.This paper presents the development and implementation of a criticalentrepreneurship course, “Entrepreneurship and the Enterprising Self” (EES),designed for master students. The course was developed with the purpose to 1)deconstruct the basic ontological assumptions that undergird the entrepreneurial logicand explore the extension and reformulation of these assumptions for various forms ofentrepreneurship, such as social entrepreneurship and ecopreneurship, 2) to analysethe broadening of enterprising subjectivities that unfold hand in hand with these formsof entrepreneurship, and 3) to go beyond these forms of entrepreneurship andsubjectivities to touch upon the (im)possibility to collectively construct new worlds.
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17. |
- Berglund, Karin, et al.
(författare)
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Transformation from entrepreneurship to entrepreneurships : creating alternatives?
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper our ambition is to provide with theoretical and empirical inspiration for studying contemporary constitutions of entrepreneurship. In specific, we seek to highlight how the transformation from entrepreneurship into forms of entrepreneurships has unfolded on various arenas. This means tracing the interplay between criticism of (traditional) entrepreneurship and the outbreak and dissemination of alternative entrepreneurships. In specific, we focus on the positive connotations that come with the alternative forms, a goodness that lures behind each and every corner, to see what it shapes as well as what shape entrepreneurship takes. Even if entrepreneurship research does pay some interest to the changing conditions for entrepreneurship, it seldom links these to changes in conditions for people, organizations and societies.
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19. |
- Berglund, Linn, et al.
(författare)
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Self-Assembly of Nanocellulose Hydrogels Mimicking Bacterial Cellulose for Wound Dressing Applications
- 2023
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:5, s. 2264-2277
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Tidskriftsartikel (refereegranskat)abstract
- The self-assembly of nanocellulose in the form of cellulose nanofibers (CNFs) can be accomplished via hydrogen-bonding assistance into completely bio-based hydrogels. This study aimed to use the intrinsic properties of CNFs, such as their ability to form strong networks and high absorption capacity and exploit them in the sustainable development of effective wound dressing materials. First, TEMPO-oxidized CNFs were separated directly from wood (W-CNFs) and compared with CNFs separated from wood pulp (P-CNFs). Second, two approaches were evaluated for hydrogel self-assembly from W-CNFs, where water was removed from the suspensions via evaporation through suspension casting (SC) or vacuum-assisted filtration (VF). Third, the W-CNF-VF hydrogel was compared to commercial bacterial cellulose (BC). The study demonstrates that the self-assembly via VF of nanocellulose hydrogels from wood was the most promising material as wound dressing and displayed comparable properties to that of BC and strength to that of soft tissue.
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20. |
- Berglund, U. W., et al.
(författare)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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21. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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22. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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24. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Key clinical milestones 15 years and onwards after DBS-STN surgery-A retrospective analysis of patients that underwent surgery between 1993 and 2001
- 2017
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Ingår i: Clinical Neurology and Neurosurgery. - : Elsevier BV. - 0303-8467. ; 154, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor fluctuations in Parkinson's disease (PD), but does not halt disease progression. The long-term deterioration of key functions such as cognition, speech, ability to swallow, gait, urinary bladder control, orientation and reality perception is decisive for patients' independency in daily life. In this paper we investigated patients with advanced PD operated at our center with STN-DBS for at least 15 years ago, in respect to key clinical milestones reflecting their overall function in daily living. Patients and methods: Retrospective analysis of clinical data concerning key clinical milestones including death in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska Hospital before January 1, 2001, were regularly assessed until death, dropout, or January 11, 2016. Results: Sixteen men and seven women with a median (range) disease duration of 18 (10-28) years were operated with STN-DBS. The median (range) follow-up time post-surgery was 12 (2-18) years and 692 person-years of disease duration were observed. In January 2016, nine PD-patients (39%) were still alive (eight with active STN-DBS). Initially, motor symptoms improved in all patients. Sustained benefit (implying active stimulation at the last follow up) was maintained in 19 of them (83%) but STN-DBS was inactivated in four (17%) due to inefficacy. Over time, all patients deteriorated slowly, and a majority developed severe non-motor and axial symptoms such as dementia, inability to talk, swallow and walk, urinary incontinence, psychosis, and need for nursing home care. At the last follow up, 16/23 (70%) patients were treated with antidepressants. Conclusion: A majority of PD-patients experience sustained motor benefit with continuous STN-DBS. However, over time, non-motor and axial symptoms slowly and severely restrict PD-patients' function in their daily living. (C) 2017 Elsevier B.V. All rights reserved.
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25. |
- Emerging Risk Factors, Collaboration, et al.
(författare)
-
The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
- 2007
-
Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
-
Tidskriftsartikel (refereegranskat)abstract
- Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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26. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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27. |
- Eskilson, Olof, 1992-, et al.
(författare)
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Nanocellulose composite wound dressings for real-time pH wound monitoring
- 2023
-
Ingår i: Materials Today Bio. - : Elsevier. - 2590-0064. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials.
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28. |
- Gad, Helge, et al.
(författare)
-
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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29. |
- Hanberg, Annika, et al.
(författare)
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Phthalates and their metabolites in human breast milk, blood and urine as measures for monitoring exposure in human risk groups
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att undersöka halter av ftalater i svenskar och vilken matris som bäst lämpar sig för hälsorelaterad miljöövervakning har ftalater och ftalatmetaboliter analyserats i en grupp kvinnor som nyligen fött barn. I samband med förlossning på Universitetssjukhuset i Lund tillfrågades förstföderskor om medverkan och 42 kvinnor kom att ingå i studien. När barnet var 2-3 veckor gammalt pumpade mamman ut 50 mL bröstmjölk. Blod- och urinprov togs en vecka senare. Omfattande förändringar av standardmetoder för provtagning av mjölk och blod gjordes för att minimera risken för kontaminering av proverna. För mjölkprovtagningen användes en specialkonstruerad manuell pump av polykarbonat med ftalatfri packning. Blodprov togs med hjälp av endast kanyl och provrör (eftersom propparna i vaccutainrör innehåller ftalater). Proverna förvarades i värmebehandlade glasbehållare och fosforsyra tillsattes för att motverka metabolism av ftalater i mjölk- och blodprover. Analyserna av bröstmjölk visade värden nära eller under detektionsgränsen (LOD) för flertalet ftalater eller deras metaboliter. Även i blod och serum var nivåerna vanligtvis nära eller under LOD. I urin analyserades endast metaboliter och dessa kunde kvantifieras i 53-100 % av proverna. Nivåerna av ftalatmetaboliter i urin hos de svenska kvinnorna var i paritet med nivåerna hos en allmänbefolkning i USA och Tyskland. Några klara korrelationer mellan nivåer i t ex urin och bröstmjölk respektive blod påvisades inte. Resultaten av studien anger att för närvarande är analys av ftalatmetaboliter i urin den mest framkomliga vägen för skattning av ftalatexponering hos människa. Provtagning och analys av mjölk och blod innebar betydligt större svårigheter. Framför allt framstår risken för kontaminering vid provtagning som betydande och en stor del av ftalaterna och dess metaboliter uppvisade låga halter, vid eller under LOD. Dessutom kan ftalater brytas ned i blod och mjölk. I flertalet internationella publicerade studier av ftalatexponering används urinmetabolit-analyser som ett mått på exponering för ftalater. I en nyligen publicerad amerikansk studie av ett 80-tal nyfödda pojkar sågs ett samband mellan kort ano-genitalt avstånd och nivåer av ftalatmetaboliter i urin hos deras mammor under graviditeten. Den amerikanska studien behöver bekräftas, men metaboliterna var desamma som i vår studie och en jämförelse visar att mediannivåerna var lägre för vissa men högre för andra metaboliter. Vår studie indikerar att svenska kvinnor i fertil ålder inte sällan exponeras för ftalater i nivåer som satts i samband med fosterpåverkan.
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30. |
- Herlitz, Johan, 1949, et al.
(författare)
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Early identification and delay to treatment in myocardial infarction and stroke: differences and similarities.
- 2010
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- The two major complications of atherosclerosis are acute myocardial infarction (AMI) and acute ischemic stroke. Both are life-threatening conditions characterised by the abrupt cessation of blood flow to respective organs, resulting in an infarction. Depending on the extent of the infarction, loss of organ function varies considerably. In both conditions, it is possible to limit the extent of infarction with early intervention. In both conditions, minutes count. This article aims to describe differences and similarities with regard to the way patients, bystanders and health care providers act in the acute phase of the two diseases with the emphasis on the pre-hospital phase.
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31. |
- Hogberg, Johan, et al.
(författare)
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Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:3, s. 334-339
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.
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32. |
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33. |
- Johansson, Charlotta, et al.
(författare)
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Planering och utformning för ett ökat gående : Litteraturstudie, expertseminarium och trafik- och stadsplanerares syn på utemiljöns förutsättningar för gångtrafik
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trafikverket (The Swedish Transport Administration) provides funding for the project"Traffic Planning to Support Increased Walking – Systematic Improvement of Conditions forTravelling by Foot ". The project studies how pedestrians choose their route, why somephenomena become obstacles/are perceived as risky or, on the contrary, encourage walking.This report, the first in the project, includes a literature review, interviews with traffic andurban planners in local government, and an expert seminar. The findings of the three studieswill then serve as a basis for further work.Interviews of local government contacts and the expert seminar are considered to be verysuccessful working methods to find out about the opinions and experience of those currentlyworking with walking-related issues. All participants have been willing to assist and to sharetheir work and experience and were aware of the role of walking in the overall transportsystem, and its part in a sustainable transport system.The study has led to the conclusion that the concepts choice of means of transport – choice ofroute –built environment (for pedestrians) have been shown to be key in the sphere ofplanning for pedestrians and walking as a mode of transport. It is also of key importance topromote walking as a mode of transport where there are positive effects on health.Society needs to give greater scope to walking-related issues and to establish the idea ofpedestrian traffic as a norm, thereby raising its status. This work also includes defining therelevant actors relating to walking-related issues.It is also of interest to make an assessment of the groups which it is easiest to encourage towalk, and to investigate and describe the difference between everyday travel for a specificpurpose, to work and school, and walking for recreation and exercise in order to be better ableto improve planning for walking as a mode of transport.There is insufficient data to describe and quantify walking and there is a lack of methods tomeasure walking. The knowledge of town planning, which is still at a general level regardingthe network and the density of the pedestrian network, should also be highlighted.The overall conclusion is that it is important to demonstrate the importance of walking, andthat walking as a mode of transport should be a normative component of planning.
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34. |
- Keselman, Boris, et al.
(författare)
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Analysis and modelling of mistriage in the Stockholm stroke triage system
- 2022
-
Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 7:2, s. 126-133
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Stockholm Stroke Triage System (SSTS) is a prehospital triage system for detection of patients eligible for endovascular thrombectomy (EVT). Assessment of hemiparesis combined with ambulance-hospital teleconsultation is used to route patients directly to the thrombectomy centre. Some patients are not identified and require secondary transport for EVT (undertriage) while others taken to the thrombectomy centre do not undergo EVT (overtriage). The aims of this study were to characterize mistriaged patients, model for and evaluate alternative triage algorithms.Patients and methods: Patients with suspected stroke transported by priority 1 ground ambulance between October 2017 and October 2018 (n = 2905) were included. Three triage algorithms were modelled using prehospital data. Decision curve analysis was performed to calculate net benefit (correctly routing patients for EVT without increasing mistriage) of alternative models vs SSTS.Results: Undertriage for EVT occurred in n = 35/2582 (1.4%) and overtriage in n = 239/323 (74.0%). Compared to correct thrombectomy triages, undertriaged patients were younger and had lower median NIHSS (10 vs 18), despite 62.9% with an M1 occlusion. In overtriaged patients, 77.0% had a stroke diagnosis (29.7% haemorrhagic). Hemiparesis and FAST items face and speech were included in all models. Decision curve analysis showed highest net benefit for SSTS for EVT, but lower for large artery occlusion (LAO) stroke.Discussion: Undertriaged patients had lower NIHSS, likely due to better compensated proximal occlusions. SSTS was superior to other models for identifying EVT candidates, but lacked information allowing comparison to other prehospital scales.Conclusion: Using prehospital data, alternative models did not outperform the SSTS in finding EVT candidates.
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35. |
- Keselman, Boris, et al.
(författare)
-
The Stockholm Stroke Triage Project : Outcomes of Endovascular Thrombectomy Before and After Triage Implementation
- 2022
-
Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 53:2, s. 473-481
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study.METHODS: We prospectively recruited patients transported by Code Stroke ambulance within the Stockholm region under the SSTS, treated with EVT during October 2017 to October 2019, and compared to EVT patients from 2 previous years.OUTCOMES: shift in modified Rankin Scale (mRS) scores, mRS score 0 to 1, mRS score 0 to 2, and death (all 3 months), National Institutes of Health Stroke Scale (NIHSS) score change 24-hour post-EVT, recanalization (Thrombolysis in Cerebral Infarction 2b-3), and symptomatic intracranial hemorrhage. mRS outcomes were adjusted for age and baseline NIHSS.RESULTS: Patients with EVT in the SSTS group (n=244) were older and had higher baseline NIHSS versus historical controls (n=187): median age 74 (interquartile range, 63-81) versus 71 (61-78); NIHSS score 17 (11.5-21) versus 15 (10-20). During SSTS, median onset-to-puncture time was 136 versus 205 minutes (P<0.001). Adjusted common odds ratio for lower mRS in SSTS patients was 1.7 (95% CI, 1.2-2.3) versus controls. During SSTS, 83/240 (34.6%) versus 44/186 (23.7%) reached 3-month mRS score 0 to 1 (P=0.014), adjusted common odds ratio 2.3 (95% CI, 1.4-3.6). Median NIHSS change 24-hour post-EVT was 6 versus 4 (P=0.005). Differences in Thrombolysis in Cerebral Infarction, symptomatic intracranial hemorrhage, and death were nonsignificant.CONCLUSIONS: With an onset to arterial puncture time reduction by 69 minutes, outcomes in thrombectomy-treated patients improved significantly after region-wide large artery occlusion triage system implementation. These results warrant replication studies in other geographic and organizational circumstances.
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36. |
- Lidén, Annika, et al.
(författare)
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Genetic counselling for cancer and risk perception
- 2003
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 42:7, s. 726-734
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Tidskriftsartikel (refereegranskat)abstract
- The main aim was to investigate risk perception and psychological distress in individuals attending genetic counselling. A consecutive series of 86 individuals with a diagnosis and/or family history of breast, ovarian or colorectal cancer was included. Risk assessments were performed before and immediately after genetic counselling and at a one-year follow-up. Psychological distress was assessed 1 week before, and 6 weeks, 6 months and 1 year after genetic counselling. The number of individuals who correctly-estimated the general risk in the population increased significantly from 35%, before to 82% after counselling (p < 0.001). One year later, data on general risk estimates showed a significant reduction of the number of correct estimations to 51%, compared with directly after the counselling (p < 0.005). In total, 54% estimated their own lifetime risk correctly after the counselling, compared with 17% before (p < 0.001) (those with a cancer diagnosis estimated the risk of their children developing cancer). One year later, the number of correct estimations had dropped to 28%. Before the counselling, the majority of the participants overestimated both the general risk and their own/children's risk. The participants experienced moderate levels of psychological distress before the counselling and a decrease of anxiety afterwards (p < 0.02). However, half of the participants reported moderate or high distress. There were no differences in psychological distress between those who estimated their risk/ children's risk as low, moderate or high or between those who over-, under- or correctly estimated their own/children's risk. Further investigations are needed to develop and adjust the risk information provided to the individual in order to avoid misunderstanding, especially as this information is going to be revealed to family members Counselling support should be offered to those individuals who experience psychological distress.
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37. |
- Lindström, Eva, et al.
(författare)
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Schizofreni - läkemedelsbehandling, patientens delaktighet och vårdens organisation : En systematisk litteraturöversikt
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Schizofreni är i de flesta fall en kronisk och invalidiserande psykisk sjukdom. Antipsykotiska läkemedel (neuroleptika) är namnet på den grupp läkemedel som är avsedd att lindra de psykotiska symtomen som uppstår vid schizofreni. Antipsykotiska läkemedel kan indelas i första generationens antipsykotika och andra generationens antipsykotika. Denna litteraturöversikt kompletterar SBU:s systematiska översikt från år 1997 med en granskning av andra generationens antipsykotika. I översikten ingår också ett kapitel om den kunskap man idag har om hur personer med schizofreni upplever sin medverkan och sin delaktighet i behandling och vård. Dessutom ingår ett kapitel där man undersökt värdet av integrerade vårdformer för personer med olika psykiatriska tillstånd där huvuddelen av dem har schizofreni.
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38. |
- Lindström, Veronica, Professor, 1966-, et al.
(författare)
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Callers' Descriptions of Stroke Symptoms during Emergency Calls in Victims Who Have Fallen or Been Found Lying Down : A Qualitative Content Analysis
- 2024
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Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- Early identification of stroke symptoms is essential. The rate of stroke identification by call-takers at emergency medical communication centres (EMCCs) varies, and patients who are found in a lying down position are often not identified as having an ongoing stroke.OBJECTIVES: this study aimed to explore signs and symptoms of stroke in patients who had fallen or were found in a lying position. DESIGN: a retrospective exploratory qualitative study design was used.METHOD: a total of 29 emergency calls to EMCCs regarding patients discharged with a stroke diagnosis from a large teaching hospital in Stockholm, Sweden, in January-June 2011, were analysed using qualitative content analysis. RESULTS: during the emergency calls, the callers described a sudden change in the patient's health status including signs such as the patient's loss of bodily control, the patient's perception of a change in sensory perception, and the callers' inability to communicate with the patient.CONCLUSIONS: The callers' descriptions of stroke in a person found in a lying position are not always as described in assessment protocols describing the onset of a stroke. Instead, the symptom descriptions are much vaguer. Therefore, to increase identification of stroke during emergency calls, there is a need for an increased understanding of how callers describe stroke symptoms and communicate with the call-takers.
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39. |
- Llona-Minguez, Sabin, et al.
(författare)
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Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1
- 2016
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:3, s. 1140-1148
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Tidskriftsartikel (refereegranskat)abstract
- The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell sternness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.
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40. |
- Llona-Minguez, Sabin, et al.
(författare)
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Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1
- 2017
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 60:5, s. 2148-2154
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Tidskriftsartikel (refereegranskat)abstract
- The dCTP pyrophosphatase 1 (dCTPase) is involved in the regulation of the cellular dNTP pool and has been linked to cancer progression. Here we report on the discovery of a series of 3,6-disubstituted triazolothiadiazoles as potent dCTPase inhibitors. Compounds 16 and 18 display good correlation between enzymatic inhibition and target engagement, together with efficacy in a cellular synergy model, deeming them as a promising starting point for hit -to-lead development.
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41. |
- Mazya, Michael V., et al.
(författare)
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Implementation of a Prehospital Stroke Triage System Using Symptom Severity and Teleconsultation in the Stockholm Stroke Triage Study
- 2020
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Ingår i: JAMA Neurology. - : American Mathematical Society (AMS). - 2168-6149 .- 2168-6157. ; 77:6, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To our knowledge, it is unknown whether a prehospital stroke triage system combining symptom severity and teleconsultation could accurately select patients for primary stroke center bypass and hasten delivery of endovascular thrombectomy (EVT) without delaying intravenous thrombolysis (IVT).Objective: To evaluate the predictive performance of the newly implemented Stockholm Stroke Triage System (SSTS) for large-artery occlusion (LAO) stroke and EVT initiation. Secondary objectives included evaluating whether the Stockholm Stroke Triage System shortened onset-to-puncture time for EVT and onset-to-needle time (ONT) for IVT.Design, Setting, and Participants: This population-based prospective cohort study conducted from October 2017 to October 2018 across the Stockholm region (Sweden) included patients transported by first-priority ("code stroke") ambulance to the hospital for acute stroke suspected by an ambulance nurse and historical controls (October 2016-October 2017). Exclusion criteria were in-hospital stroke and helicopter or private transport. Of 2909 eligible patients, 4 (0.14%) declined participation.Exposures: Patients were assessed by ambulance nurses with positive the face-arm-speech-time test or other stroke suspicion and were evaluated for moderate-to-severe hemiparesis (≥2 National Institutes of Health stroke scale points each on the ipsilateral arm and leg [A2L2 test]). If present, the comprehensive stroke center (CSC) stroke physician was teleconsulted by phone for confirmation of stroke suspicion, assessment of EVT eligibility, and direction to CSC or the nearest primary stroke center. If absent, the nearest hospital was prenotified.Main Outcomes and Measures: Primary outcome: LAO stroke. Secondary outcomes: EVT initiation, onset-to-puncture time, and ONT. Predictive performance measures included sensitivity, specificity, positive and negative predictive values, the overall accuracy for LAO stroke, and EVT initiation.Results: We recorded 2905 patients with code-stroke transports (1420 women [49%]), and of these, 323 (11%) had A2L2+ teleconsultation positive results and were triaged for direct transport to CSC (median age, 73 years [interquartile range (IQR), 64-82 years]; 55 women [48%]). Accuracy for LAO stroke was 87% (positive predictive value, 41%; negative predictive value, 93%) and 91% for EVT initiation (positive predictive value, 26%; negative predictive value, 99%). Endovascular thrombectomy was performed for 84 of 323 patients (26%) with triage-positive results and 35 of 2582 patients (1.4%) with triage-negative results. In EVT cases with a known onset time (77 [3%]), the median OPT was 137 minutes (IQR, 118-180; previous year, 206 minutes [IQR, 160-280]; n = 75) (P < .001). The regional median ONT (337 [12%]) was unchanged at 115 minutes (IQR, 83-164; previous year, 115 minutes [IQR, 85-161]; n = 360) (P = .79). The median CSC IVT door-to-needle time was 13 minutes (IQR, 10-18; 116 [4%]) (previous year, 31 minutes [IQR, 19-38]; n = 45) (P < .001).Conclusions and Relevance: The Stockholm Stroke Triage System, which combines symptom severity and teleconsultation, results in markedly faster EVT delivery without delaying IVT.
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42. |
- Michel, Maurice, et al.
(författare)
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Computational and Experimental Druggability Assessment of Human DNA Glycosylases
- 2019
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 4:7, s. 11642-11656
-
Tidskriftsartikel (refereegranskat)abstract
- Due to a polar or even charged binding interface, DNA-binding proteins are considered extraordinarily difficult targets for development of small-molecule ligands and only a handful of proteins have been targeted successfully to date. Recently, however, it has been shown that development of selective and efficient inhibitors of 8-oxoguanine DNA glycosylase is possible. Here, we describe the initial druggability assessment of DNA glycosylases in a computational setting and experimentally investigate several methods to target endonuclease VIII-like 1 (NEIL1) with small-molecule inhibitors. We find that DNA glycosylases exhibit good predicted druggability in both DNA-bound and -unbound states. Furthermore, we find catalytic sites to be highly flexible, allowing for a range of interactions and binding partners. One flexible catalytic site was rationalized for NEIL1 and further investigated experimentally using both a biochemical assay in the presence of DNA and a thermal shift assay in the absence of DNA.
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43. |
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44. |
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45. |
- Nilsson, Magnus, et al.
(författare)
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Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma
- 2022
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Ingår i: Drug Design, Development and Therapy. - : Informa Healthcare. - 1177-8881. ; 16, s. 2901-2917
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation.Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 mu g/kg and AZD4604 at 30 mu g/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]).Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model.Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.
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46. |
- Norbeck, Ola, et al.
(författare)
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Optimizing 3D EPI for rapid T1 -weighted imaging.
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 84:3, s. 1441-1455
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the use of 3D EPI for rapid T1 -weighted brain imaging, focusing on the RF pulse's influence on the contrast between gray and white matter.METHODS: An interleaved 3D EPI sequence use partial Fourier and CAIPIRINHA sampling was used to acquire T1 -weighted brain volumes with isotropic resolution, low echo times, and low geometric distortions. Five different RF pulses were evaluated in terms of fat suppression performance and gray-white matter contrast. Two binomial RF pulses were compared to a single rectangular (WE-rect) RF pulse exciting only water, and two new RF pulses developed in this work, where one was an extension of the WE-rect, and the other was an SLR pulse. The technique was demonstrated in three clinical cases, where brain tumor patients were imaged before and after gadolinium administration.RESULTS: A fat-suppressed 3D EPI sequence with a phase encoding bandwidth of around 100 Hz was found to exhibit a good trade-off between geometrical distortions and scan duration. Whole-brain T1 -weighted 3D EPI images with 1.2 mm isotropic voxel size could be acquired in 24 seconds. The WE-rect, its extension, and the SLR RF pulses resulted in reduced magnetization transfer effects and provided a 20% mean increase in gray-white matter contrast.CONCLUSION: Using a high phase encoding bandwidth and RF pulses that reduce magnetization transfer effects, a fat-suppressed multi-shot 3D EPI sequence can be used to rapidly acquire isotropic T1 -weighted volumes.
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47. |
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48. |
- Redmalm, David, 1981-, et al.
(författare)
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Möbius Management : The Internal Dynamics of Business Ethics Programmes
- 2017
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Konferensbidrag (refereegranskat)abstract
- The present study draws on the theoretical framework of Giorgio Agamben to conceptualize the dynamic that business ethics programmes create within companies—an area of study that is underexplored in organization and management research. We suggest that the “ethical” corporation can be regarded as a machine that dissolves the boundaries of the firm and conflates the goals and values of management, employees and the corporation—a process we call Möbius Management. Using ethnographic methods, we have studied the American-Hungarian IT company Prezi’s engagement in the Budapest Pride Parade, in a Roma settlement, and in a mission to help Syrian refugees. These different situations can be regarded as what Agamben calls “zones of indistinction”: places where seemingly contradictory values and categories are merged, and where the value of life is momentarily challenged. Entering these zones, employees’ personal engagement is encouraged and developed, which in turn strengthens bonds between employees and sustains an atmosphere of openness at the office. To make the interventions into company events that are also individually rewarding, management and employees downplay the political specificity of the situations in favor of emotional aspects and general references to humanist universalism. In this way, corporations with social visions can themselves also be regarded as “zones of indistinction” where idealism and economic gain, as well as individual and employee identities, are merged. In conclusion, the contrast between Prezi and the present political situation in Hungary, characterized by a rhetoric of inside and outside, accentuates the process and effect of Möbius management.
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49. |
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50. |
- Redmalm, David, 1981-, et al.
(författare)
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”Yeah! We’re Open” : Transdimensional Openness in Alternative Entrepreneurship
- 2015
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Konferensbidrag (refereegranskat)abstract
- The present ethnographic study explores the dynamics of “inside” and “outside” in diversity management and CSR. In focus is the Hungarian IT-company Prezi that engages in social issues such as gender equality, LGBT rights and anti-racism. Openness is Prezi’s watchword; by referring to themselves as open, the company aims to attract employees and foster a creative work process. Yet, to establish this openness, new insides and outsides need to be created. The study uses the work of Giorgio Agamben to trace the production of openness in various dimensions of the enterprise: boundaries between work and spare time, categorical divisions, organizational borders, and walls and other barriers in the office landscape. It is argued that while Prezi’s constellation of various types of openness is an efficient tool for social impact, the company’s production of transdimensional openness risks depoliticizing urgent social issues.
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