| 1. |
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| 2. |
- Dahlin, Lars B., et al.
(författare)
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Three-dimensional architecture of human diabetic peripheral nerves revealed by X-ray phase contrast holographic nanotomography
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.
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| 3. |
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| 4. |
- Andersson, Mariam, et al.
(författare)
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Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:52, s. 33649-33659
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Tidskriftsartikel (refereegranskat)abstract
- Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.
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| 5. |
- Hansen, Morten S., et al.
(författare)
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The association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other pain relevant brain structures—A 3-tesla MRI study of healthy men
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Central sensitization plays a pivotal role in maintenance of pain and is believed to be intricately involved in several chronic pain conditions. One clinical manifestation of central sensitization is secondary hyperalgesia. The degree of secondary hyperalgesia presumably reflects individual levels of central sensitization. The objective of this study was to investigate the association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other brain structures involved in pain processing. Materials and methods We recruited 121 healthy male participants; 118 were included in the final analysis. All participants underwent whole brain magnetic resonance imaging (MRI). Prior to MRI, all participants underwent pain testing. Secondary hyperalgesia was induced by brief thermal sensitization. Additionally, we recorded heat pain detection thresholds (HPDT), pain during one minute thermal stimulation (p-TS) and results of the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and Depression score (HADS). Results We found no significant associations between the size of the area of secondary hyperalgesia and the volume of the caudate nuclei or of the following structures: primary somatosensory cortex, anterior and mid cingulate cortex, putamen, nucleus accumbens, globus pallidus, insula and the cerebellum. Likewise, we found no significant associations between the volume of the caudate nuclei and HPDTs, p-TS, PCS and HADS. Conclusions Our findings indicate that the size of the secondary hyperalgesia area is not associated with the volume of brain structures relevant for pain processing, suggesting that the propensity to develop central sensitization, assessed as secondary hyperalgesia, is not correlated to brain structure volume.
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| 6. |
- Rinman, M-L, et al.
(författare)
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EPS - an interactive collaborative game using non-verbal communication
- 2003
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Ingår i: Proceedings of the Stockholm Music Acoustics Conference, August 6-9, 2003 (SMAC 03), Stockholm, Sweden. ; , s. 561-563
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Konferensbidrag (refereegranskat)abstract
- The interactive game environment EPS (expressive performance space), presented in this short paper, is a work still in progress. EPS involves participants in an activity using non-verbal emotional expressions. Two teams use expressive gestures in either voice or body movements to compete. Each team has an avatar controlled either by singing into a microphone or by moving in front of a video camera. Participants/players control their avatars by using acoustical or motion cues. The avatar is navigated /moving around in a 3D distributed virtual environment using the Octagon server and player system. The voice input is processed using a musical cue analysis module yielding performance variables such as tempo, sound level and articulation as well as an emotional prediction. Similarly, movements captured from the video camera are analyzed in terms of different movement cues. The target group is children aged 13- 16 and the purpose is to elaborate new forms of collaboration.
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| 7. |
- Rinman, Marie Louise, et al.
(författare)
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Ghost in the Cave : an interactive collaborative game using non-verbal communication
- 2004
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Ingår i: GESTURE-BASED COMMUNICATION IN HUMAN-COMPUTER INTERACTION. - Berlin : Springer Verlag. ; , s. 549-556
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Konferensbidrag (refereegranskat)abstract
- The interactive game environment, Ghost in the Cave, presented in this short paper, is a work still in progress. The game involves participants in an activity using non-verbal emotional expressions. Two teams use expressive gestures in either voice or body movements to compete. Each team has an avatar controlled either by singing into a microphone or by moving in front of a video camera. Participants/players control their avatars by using acoustical or motion cues. The avatar is navigated in a 3D distributed virtual environment using the Octagon server and player system. The voice input is processed using a musical cue analysis module yielding performance variables such as tempo, sound level and articulation as well as an emotional prediction. Similarly, movements captured from a video camera are analyzed in terms of different movement cues. The target group is young teenagers and the main purpose to encourage creative expressions through new forms of collaboration.
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| 8. |
- Wallin, Anders, 1950, et al.
(författare)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 9. |
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| 10. |
- Dahl, Caroline, et al.
(författare)
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Ekosystemtjänsternas bidrag till god urban livsmiljö
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Ekosystemtjänster uppmärksammas alltmer som ett viktigt inslag för en hållbar utveckling av städer och samhällen. Dessa handlar inte bara om ett miljö- och biodiversitetsperspektiv, utan också om hur ekosystemen bidrar till människans livsmiljö och stadens attraktivitet, samt de praktiska och rekreativa nyttor som befintlig och anlagd natur kan skapa i den byggda miljön.Denna rapport har tillkommit på Naturvårdsverkets initiativ, vilka också delvis har finansierat den. Arbetet har sammanfallit med ett opinionsbildande projekt, projektlett av Tankesmedjan Movium ochfinansierat av Vinnova, kallat Påverkansplattform för urbana ekosystemtjänster. Båda dessa aktiviteterhar efterfrågat kartläggning av nuläget och redovisningar av lärande exempel, varför vi har valt att arbeta integrerat med aktiviteterna. I rapporten har vi försökt att kombinera generella reflektioner med konkreta exempel. Vi har också valt att hämta lärdomar från såväl praktik som akademi och har bjudit in några av de ledande forskarna från Sveriges lantbruksuniversitet att utifrån sin forskningshorisont kommentera sådant som vi tycker oss kunna konstatera i praktiken. Det kan i något fall bli motsägelsefullt, men så är också frågan kring ekosystemtjänster i urban miljö komplext beskaffad. Som alla komplext beskaffade frågor hyser den därmed inneboende målkonflikter, åtminstone på ett generellt och övergripande plan.I rapporten konstaterar vi att det är viktigt och grundläggande att ekosystemtjänster behandlas som en tillgång för livsmiljöer i staden, och därmed också för arbetet med att planera, gestalta, anlägga och förvalta dessa miljöer. Utgångspunkten för ett sådant arbete behöver vara platsernas förutsättningar och de förväntningar som vi har på dessa miljöer. Möjligen kan det uppfattas som lite motsägelsefullt för en rapport med namnet ”Ekosystemtjänsteras bidrag till en god urban livsmiljö”, men vi är övertygande om att utgångspunkten för arbetet med ekosystemtjänster bör inte vara ekosystemtjänsterna själva, snarare en ökad platsspecifik kunskap och en ökad tydlighet kring samhällets uttalade målsättningar. Varför inleder vi med ett sådant påstående? Jo, för att påminna om att ekosystemtjänsterna utgår från oss människor och tjänsterna svarar mot våra behov. Det är alltså en slags konsumtion av tjänster som vi pratar om och som i all hållbar konsumtion handlar det om att balansera mellan tillgång och efterfrågan. Vi menar alltså att det inte alltid handlar om att maximera uttaget av en viss ekosystemtjänst, utan det handlar snarare om vilket behov som vi har identifierat på en viss plats eller i ett visst sammanhang samt hur ekosystemtjänsterna kan levererar på den platsen utifrån identifierade behov. Det är måhända en hårfin perspektivförskjutning, men vi menar att tar vi inte med oss detta synsätt in i diskussionen om ekosystemtjänster så befarar vi att vi får ett oönskat överutnyttjande av naturens ”gratistjänster”.Det pågår mycket lovvärt arbete i landet för att hitta system och verktyg som strävar efter att finna helhetssyn och mångfunktionalitet i ekosystemtjänsterna. Det finns dock en risk att verktyg blir väl generella när man försöker att fånga upp alla aspekter av hur man kan arbeta med ekosystemtjänsterna. Då riskerar implementeringsglappen också att bli för stora när generella verktyg ska appliceras på en specifik plats. Att istället lära av hur andra har gjort och ta del av varandras erfarenheter kan då vara ett värdefullt komplement och Naturvårdsverket har därför bett Tankesmedjan Movium att ta fram denna exempelsamling. Vår förhoppning är att denna rapport ska hjälpa stadsbyggnadsprocessens olika aktörer och skeden att förstå nyttan med urban natur och att ta in ekosystemtjänsterna i befintliga arbetssätt och processer.
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| 11. |
- Dahl, Christina, et al.
(författare)
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Mutual Exclusivity Analysis of Genetic and Epigenetic Drivers in Melanoma Identifies a Link Between p14(ARF) and RAR beta Signaling
- 2013
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 11:10, s. 1166-1178
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma genomes contain thousands of alterations including: mutations, copy number alterations, structural aberrations, and methylation changes. The bulk of this variation is stochastic and functionally neutral, with only a small minority representing "drivers" that contribute to the genesis and maintenance of tumors. Drivers are often directly or inversely correlated across tumors, reflecting the molecular and regulatory signaling pathways in which they operate. Here, a profile of genetic and epigenetic drivers in 110 human melanoma cell lines was generated and searched for non-random distribution patterns. Statistically significant mutual exclusivity was revealed among components of each of the p16(INK4A)-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways. In addition, an inverse correlation was observed between promoter hypermethylation of retinoic acid receptor beta (RARB) and CDKN2A alterations affecting p14(ARF) (P < 0.0001), suggesting a functional link between RAR beta signaling and the melanoma-suppressive activities of p14(ARF). Mechanistically, all-trans retinoic acid (ATRA) treatment increased the expression of p14(ARF) in primary human melanocytes and the steady-state levels of p14(ARF) in these cells were shown to be regulated via RAR beta. Furthermore, the ability of ATRA to induce senescence is reduced in p14(ARF)-depleted melanocytes, and we provide proof-of-concept that ATRA can induce irreversible growth arrest in melanoma cells with an intact RARb-p14(ARF) signaling axis, independent of p16(INK4A) and p53 status. Implications: These data highlight the power of mutual exclusivity analysis of cancer drivers to unravel molecular pathways and establish a previously unrecognized cross-talk between RAR beta and p14(ARF) with potential implications for melanoma treatment.
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| 12. |
- Dahl, Gordon B., et al.
(författare)
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Family Spillovers in Field of Study
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper estimates peer effects both from older to younger siblings and from parents to children in academic fields of study. Our setting is secondary school in Sweden, where admissions to oversubscribed fields is determined based on a student's GPA. Using an RD design, we find strong spillovers in field choices that depend on the gender mix of siblings and whether the field is gender conforming. There are also large intergenerational effects from fathers and mothers to sons, except in female-dominated fields, but little effect for daughters. These spillovers have long-term consequences for occupational segregation and wage gaps by gender.
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| 13. |
- Dahl, Gordon B., et al.
(författare)
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High School Majors and Future Earnings
- 2023
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Ingår i: American Economic Journal. - : American Economic Association. - 1945-7782 .- 1945-7790. ; 15:1, s. 351-382
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Tidskriftsartikel (refereegranskat)abstract
- We study how high school majors affect adult earnings using a regression discontinuity design. In Sweden students are admitted to majors in tenth grade based on their preference rankings and ninth grade GPA. We find engineering, natural science, and business majors yield higher earnings than social science and humanities, with major-specific returns also varying based on next-best alternatives. There is either a zero or a negative return to completing an academic program for students with a second-best nonacademic major. Most of the differences in adult earnings can be attributed to differences in occupation, and to a lesser extent, college major.
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| 14. |
- Dahl, Gordon B., et al.
(författare)
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Long-Run Returns to Field of Study in Secondary School
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper studies whether specialized academic fields of study in secondary school, which are common in many countries, affect earnings as an adult. Identification is challenging, because it requires not just quasi-random variation into fields of study, but also an accounting of individuals’ next-best alternatives. Our setting is Sweden, where at the end of ninth grade students rank fields of study and admissions to oversubscribed fields is determined based on a student’s GPA. We use a regression discontinuity design which allows for different labor market returns for each combination of preferred versus next-best choice, together with nationwide register data for school cohorts from 1977-1991 linked to their earnings as adults. Our analysis yields four main findings. First, Engineering, Natural Science, and Business yield higher earnings relative to most second-best choices, while Social Science and Humanities result in sizable drops, even relative to non-academic vocational programs. Second, the return to completing a field varies substantially as a function of a student’s next-best alternative. The magnitudes are often as large as estimates of the return to two years of additional education. Third, the pattern of returns for individuals with different first and second best choices is consistent with comparative advantage for many field choice combinations, while others exhibit either random sorting or comparative disadvantage. Fourth, most of the differences in adult earnings can be attributed to differences in college major and occupation. Taken together, these results highlight that the field choices students make at age 16, when they may have limited information about their skills and the labor market, have effects which last into adulthood.
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| 15. |
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| 16. |
- Foss, Stein, et al.
(författare)
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First Scandinavian Protocol for Controlled Donation After Circulatory Death Using Normothermic Regional Perfusion
- 2018
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Ingår i: Transplantation direct. - : LIPPINCOTT WILLIAMS & WILKINS. - 2373-8731. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- Background. Donation after circulatory death (DCD) can increase the pool of available organs for transplantation. This pilot study evaluates the implementation of a controlled DCD (cDCD) protocol using normothermic regional perfusion in Norway. Methods. Patients aged 16 to 60 years that are in coma with documented devastating brain injury in need of mechanical ventilation, who would most likely attain cardiac arrest within 60 minutes after extubation, were eligible. With the acceptance from the next of kin and their wish for organ donation, life support was withdrawn and cardiac arrest observed. After a 5-minute no-touch period, extracorporeal membrane oxygenation for post mortem regional normothermic regional perfusion was established. Cerebral and cardiac reperfusion was prevented by an aortic occlusion catheter. Measured glomerular filtration rates 1 year postengraftment were compared between cDCD grafts and age-matched grafts donated after brain death (DBD). Results. Eight cDCD were performed from 2014 to 2015. Circulation ceased median 12 (range, 6-24) minutes after withdrawal of life-sustaining treatment. Fourteen kidneys and 2 livers were retrieved and subsequently transplanted. Functional warm ischemic time was 26 (20-51) minutes. Regional perfusion was applied for 97 minutes (54-106 minutes). Measured glomerular filtration rate 1 year postengraftment was not significantly different between cDCD and donation after brain death organs, 75 (65-76) vs 60 (37-112) mL/min per 1.73 m(2) (P = 0.23). No complications have been observed in the 2 cDCD livers. Conclusion. A protocol for cDCD is successfully established in Norway. Excellent transplant outcomes have encouraged us to continue this work addressing the shortage of organs for transplantation.
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| 17. |
- Ilander, M, et al.
(författare)
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Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:5, s. 1108-1116
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.Leukemia advance online publication, 16 December 2016; doi:10.1038/leu.2016.360.
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| 18. |
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| 19. |
- Melin, Malin, et al.
(författare)
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Constitutional downregulation of SEMA5A expression in autism.
- 2006
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 54:1, s. 64-9
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Tidskriftsartikel (refereegranskat)abstract
- There is strong evidence for the importance of genetic factors in idiopathic autism. The results from independent twin and family studies suggest that the disorder is caused by the action of several genes, possibly acting epistatically. We have used cDNA microarray technology for the identification of constitutional changes in the gene expression profile associated with idiopathic autism. Samples were obtained and analyzed from 6 affected subjects belonging to multiplex autism families and from 6 healthy controls. We assessed the expression levels for approximately 7,700 genes by cDNA microarrays using mRNA derived from Epstein-Barr virus-transformed B lymphocytes. The microarray data were analyzed in order to identify up- or downregulation of specific genes. A common pattern with nine downregulated genes was identified among samples derived from individuals with autism when compared to controls. Four of these nine genes encode proteins involved in biological processes associated with brain function or the immune system, and are consequently considered as candidates for genes associated with autism. Quantitative real-time PCR confirms the downregulation of the gene encoding SEMA5A, a protein involved in axonal guidance. Epstein-Barr virus should be considered as a possible source for altered expression, but our consistent results make us suggest SEMA5A as a candidate gene in the etiology of idiopathic autism.
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| 20. |
- Mälarstig, Anders, et al.
(författare)
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Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
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| 21. |
- Rooth, Dan-Olof, 1967-, et al.
(författare)
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Intergenerational and Sibling Spillovers in High School Majors
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper estimates family spillovers in high school major choice in Sweden, where admission to oversubscribed majors is determined based on GPA. Using a regression discontinuity design, we find large sibling and intergenerational spillovers that depend on the gender mix of a dyad. Same-gender siblings copy one another, while younger brothers recoil from older sister's choices. Fathers and mothers influence sons, but not their daughters, except when a mother majors in the male-dominated program of Engineering. Back of the envelope calculations reveal these within family spillovers have sizable implications for the gender composition of majors.
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| 22. |
- Steffensen, Jörgen Peder, et al.
(författare)
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High-Resolution Greenland Ice Core Data Show Abrupt Climate Change Happens in Few Years
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 321, s. 680-684
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Tidskriftsartikel (refereegranskat)abstract
- The last two abrupt warmings at the onset of our present warm interglacial period, interrupted bythe Younger Dryas cooling event, were investigated at high temporal resolution from the NorthGreenland Ice Core Project ice core. The deuterium excess, a proxy of Greenland precipitationmoisture source, switched mode within 1 to 3 years over these transitions and initiated a moregradual change (over 50 years) of the Greenland air temperature, as recorded by stable waterisotopes. The onsets of both abrupt Greenland warmings were slightly preceded by decreasingGreenland dust deposition, reflecting the wetting of Asian deserts. A northern shift of theIntertropical Convergence Zone could be the trigger of these abrupt shifts of Northern Hemisphereatmospheric circulation, resulting in changes of 2 to 4 kelvin in Greenland moisture sourcetemperature from one year to the next.
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