| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Donis, Daphne, et al.
(författare)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Tidskriftsartikel (refereegranskat)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 3. |
- Franzmeier, Nicolai, et al.
(författare)
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Earlier Alzheimer's disease onset is associated with a shift of tau pathology towards brain hubs which facilitates tau spreading
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:S1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Alzheimer’s disease (AD), younger symptom onset is associated accelerated cognitive decline and tau spreading, yet the drivers of faster disease manifestation in patients with earlier symptom onset are unknown. Earlier symptom onset is associated with stronger tau pathology in fronto-parietal regions which typically harbor globally connected hubs that are central for cognition. Since tau spreads across connected regions, globally connected hubs may accelerate tau spreading due to their large number of connections to other brain regions. Thus, we hypothesized that a pattern shift of tau pathology towards globally connected brain hubs may facilitate tau spreading and earlier symptom manifestation in AD. Method: We included two independent samples with longitudinal Flortaucipir tau-PET covering the AD spectrum (ADNI: n(controls/AD-preclinical/AD-symptomatic)=93/60/89, BioFINDER, n(controls/AD-preclinical/AD-symptomatic)=16/16/25). In addition, we included resting-state fMRI from human connectome project participants (n=1000), applying a 200-ROI brain atlas to obtain a global connectivity map for assessing brain hubs (Fig.1A-D). Applying the same atlas to tau-PET we transformed SUVRs to tau positivities using a pre-established gaussian-mixture modeling approach (Fig.1E-F). By mapping tau-PET positivities to the fMRI-derived global connectivity map (Fig.1G-L), we assessed the degree to which subject specific tau-PET patterns were shifted towards globally connected hubs or non-hubs, while adjusting for global tau levels. Using linear regression, we then tested whether a stronger shift of tau towards hubs was associated with earlier symptom manifestation and faster longitudinal tau accumulation. Result: In symptomatic AD patients, younger age was associated with a stronger shift of tau-PET towards globally connected brain hubs (p[ADNI/BiOFINDER]=0.024/0.018, Fig.2A&B), and with higher global connectivity of epicenters with highest tau pathology (p[ADNI/BiOFINDER]<0.001/0.001, Fig.2C&D). In symptomatic AD, younger age (p[ADNI/BiOFINDER]=0.009/0.001) and a stronger shift of tau-PET towards hubs predicted faster subsequent tau accumulation (p[ADNI/BiOFINDER]=0.004/0.002), supporting the view that that hubs facilitate tau spreading (Fig.3). Further, a stronger shift of tau-PET towards globally connected brain hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients (p[ADNI/BiOFINDER]=0.039/0.046). Conclusion: Younger AD symptom onset is associated with stronger tau pathology in globally connected brain hubs, which facilitates faster tau spreading.
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| 4. |
- Frontzkowski, Lukas, et al.
(författare)
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Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.
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| 5. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 6. |
- Scaini, Anna, et al.
(författare)
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Pathways from research to sustainable development: Insights from ten research projects in sustainability and resilience
- 2024
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Ingår i: AMBIO. - : SPRINGER. - 0044-7447 .- 1654-7209.
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Tidskriftsartikel (refereegranskat)abstract
- Drawing on collective experience from ten collaborative research projects focused on the Global South, we identify three major challenges that impede the translation of research on sustainability and resilience into better-informed choices by individuals and policy-makers that in turn can support transformation to a sustainable future. The three challenges comprise: (i) converting knowledge produced during research projects into successful knowledge application; (ii) scaling up knowledge in time when research projects are short-term and potential impacts are long-term; and (iii) scaling up knowledge across space, from local research sites to larger-scale or even global impact. Some potential pathways for funding agencies to overcome these challenges include providing targeted prolonged funding for dissemination and outreach, and facilitating collaboration and coordination across different sites, research teams, and partner organizations. By systematically documenting these challenges, we hope to pave the way for further innovations in the research cycle.
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| 7. |
- Ahlqvist, Emma, et al.
(författare)
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A link between GIP and osteopontin in adipose tissue and insulin resistance.
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2088-2094
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Tidskriftsartikel (refereegranskat)abstract
- Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.
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| 8. |
- Andersson, Anna, et al.
(författare)
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Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia.
- 2009
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 34:3, s. 556-65
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Tidskriftsartikel (refereegranskat)abstract
- Even though ammonia is considered to underlie nervous system symptoms of dysfunction during hyperammonemia, lactate, which increases as a metabolic consequence of high ammonia levels, might also be a contributing factor. The data presented here show that NH4Cl (5 mM) mediates astroglial cell swelling, and that treatment with NH4Cl or lactate (25 mM) causes rearrangements of actin filaments and reduces astroglial glutamate uptake capacity. Co-application with BaCl2, which blocks astroglial uptake of NH4+, prevents NH4Cl-mediated cell swelling and rearrangement of actin filaments, but does not reduce NH4Cl-induced glutamate uptake capacity inhibition. Neither NH4Cl nor lactate affected glutamate uptake or protein expression in microglial cultures, indicating that astroglial cells are more susceptible to the neurotoxic affects of ammonia. Our results suggest that ammonium underlies brain edema, but that lactate can contribute to some of the cellular dysfunctions associated with elevated cerebral levels of ammonia.
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| 9. |
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| 10. |
- Bergman, Lina, 1982, et al.
(författare)
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Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
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Tidskriftsartikel (refereegranskat)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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| 11. |
- Bergman, Peter, et al.
(författare)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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| 12. |
- Bocancea, Diana I., et al.
(författare)
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Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
- 2023
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:9, s. 3719-3734
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We employed a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET.In this multicenter study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease-dementia with baseline [18F]flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning.We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness.In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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| 17. |
- Ellerstrand, Simon Jacobsen, et al.
(författare)
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Weak population genetic structure in Eurasian spruce bark beetle over large regional scales in Sweden
- 2022
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- The Eurasian spruce bark beetle, Ips typographus, is a major pest, capable of killing spruce forests during large population outbreaks. Recorded dispersal distances of individual beetles are typically within hundreds of meters or a few kilometers. However, the connectivity between populations at larger distances and longer time spans and how this is affected by the habitat is less studied, despite its importance for understanding at which distances local outbreaks may spread. Previous population genetic studies in I. typographus typically used low resolution markers. Here, we use genome-wide data to assess population structure and connectivity of I. typographus in Sweden. We used 152 individuals from 19 population samples, distributed over 830 km from Strömsund (63° 46′ 8″ N) in the north to Nyteboda (56° 8′ 50″ N) in the south, to capture processes at a large regional scale, and a transect sampling design adjacent to a recent outbreak to capture processes at a smaller scale (76 km). Using restriction site-associated DNA sequencing (RADseq) markers capturing 1409–1997 SNPs throughout the genome, we document a weak genetic structure over the large scale, potentially indicative of high connectivity with extensive gene flow. No differentiation was detected at the smaller scale. We find indications of isolation-by-distance both for relative (FST) and absolute divergence (Dxy). The two northernmost populations are most differentiated from the remaining populations, and diverge in parallel to the southern populations for a set of outlier loci. In conclusion, the population structure of I. typographus in Sweden is weak, suggesting a high capacity to disperse and establish outbreak populations in new territories.
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| 18. |
- Franzmeier, Nicolai, et al.
(författare)
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Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:48
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Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer's disease (AD), the Braak staging scheme suggests a stereotypical tau spreading pattern that does, however, not capture interindividual variability in tau deposition. This complicates the prediction of tau spreading, which may become critical for defining individualized tau-PET readouts in clinical trials. Since tau is assumed to spread throughout connected regions, we used functional connectivity to improve tau spreading predictions over Braak staging methods. We included two samples with longitudinal tau-PET from controls and AD patients. Cross-sectionally, we found connectivity of tau epicenters (i.e., regions with earliest tau) to predict estimated tau spreading sequences. Longitudinally, we found tau accumulation rates to correlate with connectivity strength to patient-specific tau epicenters. A connectivity-based, patient-centered tau spreading model improved the assessment of tau accumulation rates compared to Braak stage-specific readouts and reduced sample sizes by ~40% in simulated tau-targeting interventions. Thus, connectivity-based tau spreading models may show utility in clinical trials.
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| 19. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 20. |
- Gourdon, Pontus Emanuel, 1978, et al.
(författare)
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Optimized in vitro and in vivo expression of proteorhodopsin: A seven-transmembrane proton pump
- 2008
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1096-0279 .- 1046-5928. ; 58:1, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- Proteorhodopsin is an integral membrane light-harvesting proton pump that is found in bacteria distributed throughout global surface waters. Here, we present a protocol for functional in vitro production of pR using a commercial cell-free synthesis system yielding 1.0 mg purified protein per milliliter of cell lysate. We also present an optimized protocol for in vivo over-expression of pR in Escherichia coli, and a two-step purification yielding 5 mg of essentially pure functional protein per liter of culture. Both approaches are straightforward, rapid, and easily scalable. Thus either may facilitate the exploitation of pR for commercial biotechnological applications. Finally, the implications of some observations of the in vitro synthesis behavior, as well as preliminary results towards a structural determination of pR are discussed.
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| 21. |
- Hansson, I, et al.
(författare)
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Cow characteristics associated with the variation in number of contacts between dairy cows
- 2023
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Ingår i: Journal of Dairy Science. - : Elsevier Inc.. - 0022-0302 .- 1525-3198. ; 106:4, s. 2685-
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Tidskriftsartikel (refereegranskat)abstract
- In modern freestall barns where large groups of cows are housed together, the behavior displayed by herd mates can influence the welfare and production of other individuals. Therefore, understanding social interactions in groups of dairy cows is important to enhance herd management and optimize the outcomes of both animal health and welfare in the future. Many factors can affect the number of social contacts in a group. This study aimed to identify which characteristics of a cow are associated with the number of contacts it has with other group members in 2 different functional areas (feeding and resting area) to increase our understanding of the social behavior of dairy cows. Inside 2 herds housed in freestall barns with around 200 lactating cows each, cow positions were recorded with an ultra-wideband real-time location system collecting all cows' positions every second over 2 wk. Using the positioning data of the cows, we quantified the number of contacts between them, assuming that cows spending time in proximity to one another (within a distance of 2.5 m for at least 10 min per day) were interacting socially. We documented in which barn areas these interactions occurred and used linear mixed models to investigate if lactation stage, parity, breed, pregnancy status, estrus, udder health, and claw health affect the number of contacts. We found variation in the number of contacts a cow had between individuals in both functional areas. Cows in later lactation had more contacts in the feeding area than cows in early lactation. Furthermore, in one herd, higher parity cows had fewer contacts in the feeding area than first parity cows, and in the other herd, cows in third parity or higher had more contacts in the resting area. This study indicates that cow characteristics such as parity and days in milk are associated with the number of contacts a cow has daily to its herd mates and provides useful information for further research on social interactions of dairy cows.
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| 24. |
- Holst-Hansson, Annette, et al.
(författare)
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The breath of life : womens' experiences of breathing adapted radiation therapy
- 2013
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 17:3, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To describe and analyze how women with breast cancer experience breathing adapted radiation therapy (BART) and to explore how women manage daily radiation therapy. Method Individual interviews were conducted with 20 women treated with BART for breast cancer concerning their perception of radiation therapy. The transcribed interviews were analyzed using qualitative content analysis. Results ‘The breath of life’ was the overall theme, as the women experienced the breathing as a way in which to influence their treatment and thus their survival. ‘Participating in one's treatment, for good or ill’, was the main category with four subcategories, ‘Knowing one has done something good’, ‘Getting an extra bonus – healthwise’, ‘The experience of being in control’ and ‘Being in a high-technology environment’. The breathing technique became the strategy by which they could manage their treatment and gave them a sense of participation which led to a feeling of being in control. The women also felt that breathing benefited their health both mentally and physically. The high-technology environment was experienced as both hopeful and frightening. Conclusion Survival or increasing the chances of survival, are of ultimate importance for a woman with breast cancer. BART requires commitment from the women, which was perceived as offering them an opportunity to participate in their own treatment, for their survival. Increasing the women's possibilities to participate in their treatment benefits their health and welfare during an otherwise turbulent time and allow the rehabilitation process to start during treatment.
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| 25. |
- Jammer, Ib, et al.
(författare)
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Medical services of a mulicultural summer camp event: experiences from the 22nd World Scout Jamboree, Sweden 2011
- 2013
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prevention and treatment of medical issues are the main task of a health service at a youth camp. However, only few reports about organisation and implementation of camp health care are available. This makes it difficult for future camp directors to plan and estimate the health care needed for a certain camp size. We summarize the experience in planning and running health care for the 22nd World Scout Jamboree (WSJ) 2011 in Sweden. Methods: During the WSJ, 40,061 participants from 146 nations were gathered in southern Sweden to a 12 day summer camp. Another 31,645 people were visitors. Members for the medical service were 153 volunteering medical professionals with different language and cultural backgrounds from 18 different countries. Results: Of 40,061 participants 2,893 (7.3%) needed medical assistance. We found an equal distribution of cases to approximately one third surgical, one third medical and one third unspecified cases. Much energy was spent on health prevention, hygiene measures and organizing of psychological support. Conclusions: A youth camp with a multicultural population and a size of a small city demands flexible staff with high communication skills. Special attention should be paid in prevention of contagious diseases and taking care of psychological issues.
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| 26. |
- Levin, Malin, 1973, et al.
(författare)
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Rip2 deficiency leads to increased atherosclerosis despite decreased inflammation.
- 2011
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Ingår i: Circulation research. - 1524-4571. ; 109:11, s. 1210-8
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Tidskriftsartikel (refereegranskat)abstract
- The innate immune system and in particular the pattern-recognition receptors Toll-like receptors have recently been linked to atherosclerosis. Consequently, inhibition of various signaling molecules downstream of the Toll-like receptors has been tested as a strategy to prevent progression of atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, including Toll-like receptors, and is therefore an interesting potential target for pharmaceutical intervention.
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| 27. |
- Lyssenko, Valeriya, et al.
(författare)
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Pleiotropic Effects of GIP on Islet Function Involve Osteopontin
- 2011
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:9, s. 2424-2433
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011
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| 28. |
- Löfstrand, Jonas, 1981, et al.
(författare)
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Long-term patient-reported back and shoulder function after delayed breast reconstruction with a latissimus dorsi flap: case-control cohort study.
- 2024
-
Ingår i: The British journal of surgery. - 1365-2168. ; 111:1
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Tidskriftsartikel (refereegranskat)abstract
- Sacrifice of the latissimus dorsi (LD) muscle might entail donor site morbidity when used in delayed breast reconstruction. Previous studies are small, have short follow-up, and demonstrate diverging results. The aims of this study were to evaluate long-term patient-reported effects on shoulder and back function following LD flap harvest, and to investigate predictors for a worse outcome.This is a retrospective observational case-control cohort study. Cases were all patients who had undergone an LD flap reconstruction during the years 2007-2017. Controls were patients reconstructed with a deep inferior epigastric perforator (DIEP) flap during the same time period. Participants completed two validated questionnaires; the BREAST-Q reconstruction LD domains and the Western Ontario Shoulder Osteoarthritis Index (WOOS).A total of 135 cases (75 per cent) and 118 controls (60 per cent) responded to the questionnaires. The mean follow-up time was 7 years. Patients reconstructed with a LD flap were significantly less satisfied with their back and shoulder function when compared to the DIEP controls, as measured with BREAST-Q and WOOS. Predictors for a poor patient-reported back and shoulder function included axillary surgery and axillary radiotherapy, especially when combined, as well as higher age at reconstruction.Patients who have undergone LD flap for delayed breast reconstruction had a lower satisfaction with back and shoulder function, when compared to patients who had undergone a DIEP reconstruction. Delayed LD reconstruction should be used with care, especially in patients who have undergone axillary surgery and axillary radiotherapy.
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| 29. |
- Mantzouki, Evanthia, et al.
(författare)
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
- 2018
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Ingår i: Toxins. - : MDPI. - 2072-6651. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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| 30. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Biological and environmental predictors of heterogeneity in neurocognitive ageing : Evidence from Betula and other longitudinal studies
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 64
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Forskningsöversikt (refereegranskat)abstract
- Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.
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| 31. |
- Osvalder, Anna-Lisa, 1961, et al.
(författare)
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Older Children’s Sitting Postures, Behaviour and Comfort Experience during Ride – A Comparison between an Integrated Booster Cushion and a High-Back Booster
- 2013
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Ingår i: Proceedings 2013 IRCOBI Conference, 11-13 September, Gothenburg, Sweden. - 2235-3151. ; , s. 882-885
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Konferensbidrag (refereegranskat)abstract
- Sitting postures and comfort experience were analysed from six children aged 7-9 (131-145 cm) seated on an Integrated Booster Cushion (IBC) and a high-back Booster (hbB) during 1 hour on-road drives respectively. Data was collected from video recordings, questionnaires and interviews. When seated on the IBC the most frequent posture was with the entire back and shoulders against the backrest and the head upright. On the hbB, the shoulders were seldom against the backrest. The most frequent lateral sitting posture for both boosters was upright with the seat belt in contact with the neck or mid-shoulder. Moderate and extreme forward and lateral postures occurred occasionally. A positive attitude was found towards the IBC due to possibilities to move freely, the soft seat cushion and the absence of torso supports, but the short seat cushion created some inconvenience. The hbB was perceived hard, created a locked-in feeling and felt unpleasant due to movements when changing postures. The combination of objective and subjective measures provided valuable information regarding children’s sitting behaviour. It is obvious that children do not always sit as in crash tests. Their activities and perceived discomfort influenced the selection of sitting posture and seat belt positions.
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| 32. |
- Persson, Carina Ulla, 1970, et al.
(författare)
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Responsiveness of a modified version of the postural assessment scale for stroke patients and longitudinal change in postural control after stroke- Postural Stroke Study in Gothenburg (POSTGOT) -
- 2013
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Ingår i: Journal of neuroengineering and rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Responsiveness data certify that a change in a measurement output represents a real change, not a measurement error or biological variability. The objective was to evaluate the responsiveness of the modified version of the Postural Assessment Scale for Stroke Patients (SwePASS) in patients with a first event of stroke. An additional aim was to estimate the change in postural control during the first 12 months after stroke onset. METHODS: The SwePASS assessments were conducted during the first week and 3, 6 and 12 months after stroke in 90 patients. Svensson's method, Relative Position (RP), Relative Concentration (RC) and Relative Rank Variance (RV), were used to estimate the scale's responsiveness and the patients' change in postural control over time. RESULTS: From the first week to 3 months after stroke, the patients improved in terms of postural control with 2 to 12 times larger systematic changes in Relative Position (RP), for which 9 items and the total score showed a significant responsiveness to change when compared to the interrater reliability measurement error of the SwePASS reported in a previous study. When SwePASS was used to assess change in postural control between the first week and 3 months, 74% of the patients received higher scores while 10% received lower scores, RP 0.31 (95% CI 0.219-0.402). The corresponding figures between 3 and 6 and between 6 and 12 months were 37% and 16%, RP 0.09 (95% CI 0.030-0.152), and 18% and 26%, RP -0.07 (95% CI -0.134- (-0.010)), respectively. CONCLUSIONS: The SwePASS is responsive to change. Postural control evaluated using the SwePASS showed an improvement during the first 6 months after stroke. The measurement property, in the form of responsiveness, shows that the SwePASS scoring method can be considered for use in rehabilitation when assessing postural control in patients after stroke, especially during the first 3 months.
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| 33. |
- Persson, Carina Ulla, 1970, et al.
(författare)
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Timed Up & Go as a measure for longitudinal change in mobility after stroke - Postural Stroke Study in Gothenburg (POSTGOT)
- 2014
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Ingår i: Journal of NeuroEngineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 11:83
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background A frequently used clinical test to assess mobility after stroke is the Timed Up & Go. Knowledge regarding whether or not the Timed Up & Go is able to detect change over time in patients with stroke, whether improvements in mobility exist after the first three months and whether or not longitudinal change in mobility after stroke depend on the patients’ age, is limited or unclear. The objectives were to investigate the distribution-based responsiveness of the Timed Up & Go (TUG) during the first three months after a first event of stroke, to measure the longitudinal change in TUG time during the first year after stroke and to establish whether recovery in TUG time differs between different age groups. Methods Ninety-one patients with first-ever stroke were assessed using the Timed Up & Go at the 1st week and at 3, 6 and 12 months after stroke. The non-parametric sign-test, the parametric t-test and a mixed model approach to linear regression for repeated measurements (Proc mixed) were used for the statistical analyses. Results The median TUG time was reduced from 17 to 12 seconds (p < 0.001) between the 1st week and 3 months. No further improvement was seen between 3 and 12 months after stroke. In a mixed model approach to linear regression, there was a significant age difference. Patients at age 80 and above tended to deteriorate in terms of TUG time between 3 and 12 months after stroke, while patients < 80 years did not (p = 0.011 for the interaction between age group and time). Conclusion The Timed Up & Go demonstrates ability to detect change in mobility over time in patients with stroke. A significant improvement in TUG time from the 1st week to 3 months after stroke was found, as expected, but thereafter no statistically significant change was detected. After 3 months, patients ≥80 years tended to deteriorate in terms of TUG time, while the younger patients did not.
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| 34. |
- Rubinski, Anna, et al.
(författare)
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Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease
- 2022
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels—which differ substantially between white matter tracts in the brain—are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD. Methods: We included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI: n = 275; BioFINDER-1: n = 102) and longitudinally in a subset (ADNI: n = 123, mean FU = 1.53 [0.69–3.95] years; BioFINDER-1: n = 39, mean FU = 1.87 [1.21–2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs. Results: We found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho = − 0.267, p < 0.001; BioFINDER-1: rho = − 0.175, p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI: β = − 0.185, p < 0.001; BioFINDER-1: β = − 0.166, p < 0.001). Conclusion: Higher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms.
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| 35. |
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| 36. |
- Sjörs Dahlman, Anna, 1981-, et al.
(författare)
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In-vehicle fragrance administration as a countermeasure for driver fatigue
- 2022
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Ingår i: Road Safety on Five Continents – RS5C. Proceedings. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 70-71
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Driver fatigue is a contributing factor in about 20% of all crashes. Prevention of fatigue related crashes is a major goal for the automotive industry. To reach this goal, both robust detection and effective countermeasures are required. The most effective countermeasure for sleepiness is sleep. Studies also show an increased alertness using caffein intake. Despite this, the most common countermeasure used is to stop to take a walk, turn on the radio/stereo or open a window. Countermeasures for fatigue may be a larger challenge than detection, since the most effective countermeasure, such as taking a nap, are highly intrusive in the sense that you need to make an unplanned stop (or shift drivers if there is more than one person in the car). Finding less intrusive, yet effective, countermeasures that could be deployed without requiring major replanning would thus provide a significant benefit to car makers who wish to deploy this type of technology in their vehicles.In the current study, the possibility of exposing drivers to odors when they are about to fall asleep has been explored. Previous research has found that specific fragrances can have alerting effects and that certain substances that act on trigeminal nerves can wake people from both light and deeper sleep. Therefore, the aim was to investigate if administration of a fragrance incorporating trigeminal components during fatigued driving can have a significant alerting effect.
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| 37. |
- Sylvan, Sandra Eketorp, et al.
(författare)
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First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
- 2019
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Ingår i: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
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| 38. |
- TEDDY study group, The, et al.
(författare)
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The environmental determinants of diabetes in the young (TEDDY) study: Study design
- 2007
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 8:5, s. 286-298
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361 588 newborns, of which it is anticipated that 17 804 will be eligible for enrollment with just over 7800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM.
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| 39. |
- Tolmachev, Vladimir, et al.
(författare)
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Imaging of EGFR expression in murine xenografts using site-specifically labelled anti-EGFR In-111-DOTA-Z(EGFR:2377) Affibody molecule : aspect of the injected tracer amount
- 2010
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 37:3, s. 613-622
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of epidermal growth factor receptor (EGFR) is a prognostic and predictive biomarker in a number of malignant tumours. Radionuclide molecular imaging of EGFR expression in cancer could influence patient management. However, EGFR expression in normal tissues might complicate in vivo imaging. The aim of this study was to evaluate if optimization of the injected protein dose might improve imaging of EGFR expression in tumours using a novel EGFR-targeting protein, the DOTA-Z(EGFR:2377) Affibody molecule. An anti-EGFR Affibody molecule, Z(EGFR:2377), was labelled with In-111 via the DOTA chelator site-specifically conjugated to a C-terminal cysteine. The affinity of DOTA-Z(EGFR:2377) for murine and human EGFR was measured by surface plasmon resonance. The cellular processing of In-111-DOTA-Z(EGFR:2377) was evaluated in vitro. The biodistribution of radiolabelled Affibody molecules injected in a broad range of injected Affibody protein doses was evaluated in mice bearing EGFR-expressing A431 xenografts. Site-specific coupling of DOTA provided a uniform conjugate possessing equal affinity for human and murine EGFR. The internalization of In-111-DOTA-Z(EGFR:2377) by A431 cells was slow. In vivo, the conjugate accumulated specifically in xenografts and in EGFR-expressing tissues. The curve representing the dependence of tumour uptake on the injected Affibody protein dose was bell-shaped. The highest specific radioactivity (lowest injected protein dose) provided a suboptimal tumour-to-blood ratio. The results of the biodistribution study were confirmed by gamma-camera imaging. The In-111-DOTA-Z(EGFR:2377) Affibody molecule is a promising tracer for radionuclide molecular imaging of EGFR expression in malignant tumours. Careful optimization of protein dose is required for high-contrast imaging of EGFR expression in vivo.
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| 40. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 41. |
- Wenzel, Ulf Alexander, 1975, et al.
(författare)
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Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC.
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| 42. |
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| 43. |
- Winqvist, Maria, et al.
(författare)
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Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group
- 2016
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Ingår i: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 101:12, s. 1573-1580
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Tidskriftsartikel (refereegranskat)abstract
- Ibrutinib, a Brutons tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy amp;gt;= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richters transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.
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| 44. |
- Ytreberg, Agnes, et al.
(författare)
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God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 3: Övervakningsprogram
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att fastställa övervakningsprogram.God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för elva temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. Utifrån de elva deskriptorerna har Sverige fastställt 13 övervakningsprogram. Sex program utgår ifrån olika biodiversitetsteman som berörs av en upp till tre deskriptorer, medan de övriga sju programmen utgår ifrån de deskriptorer som är mer inriktade mot belastning och miljöförändring.För varje program har ett antal underprogram föreslagits baserat på den nuvarande övervakningen och/eller planerad övervakning. Övervakning som ingår i programmen ska vara pågående och data ska vara tillgängliga. I programmen ingår nationell och regional miljöövervakning inklusive verksamhetsutövares recipientkontroll. Dessutom ingår annan typ av datainsamling som till exempel inventeringar av tumlare och uppgifter om omfattningen av mänskliga aktiviteter som orsakar belastning och miljöförändringar. Enligt havsmiljödirektivet ska övervakningen fånga upp tillstånd och miljöförändringar, belastning och omfattning av aktiviteterna som orsakar belastningen samt effekter av åtgärder. Eftersom nästa steg i havsförvaltningscykeln är att fastställa åtgärdsprogram kommer övervakning för att följa upp åtgärder att läggas till övervakningsprogrammen först under nästa förvaltningscykel.I beskrivningarna av programmen framgår hur den nuvarande övervakningen motsvarar de krav som ställs på dataunderlag genom havsmiljödirektivets bilaga III samt genom deskriptorer, kriterier, indikatorer och beslutade miljökvalitetsnormer. I dagens övervakning saknas bland annat tillräcklig övervakning för uppföljning av livsmiljöers tillstånd och utbredning. För marint avfall, buller och främmande arter saknas nationellt samordnad övervakning, men det görs regionala insatser och ett antal projekt har genomförts eller påbörjats för att öka kunskapen om hur övervakning bäst ska utformas. För de program som har pågående övervakning beskrivs utvecklingsbehoven för att förbättra underlaget för de återkommande tillståndsbedömningarna.Övervakningsprogrammet som fastställs under 2014 utgör således inte ett fast program för kunskapsinhämtning. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där utveckling av indikatorer och övervakning kommer att ske kontinuerligt.
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| 45. |
- Zaigham, Mehreen, et al.
(författare)
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Intrauterine vertical SARS-CoV-2 infection : a case confirming transplacental transmission followed by divergence of the viral genome
- 2021
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Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 128:8, s. 1388-1394
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Tidskriftsartikel (refereegranskat)abstract
- A 27-year-old woman (gravida 2, para 1) was transported to the regional university hospital in gestational week (GW) 34 + 4 due to a three-day history of fever, abdominal pain and reduced foetal movements. She had developed a dry cough one day prior to the admission (Figure S1). The woman, was slightly overweight (BMI 27 kg/m2 ) but otherwise healthy. She had normal antenatal check-ups and an obstetric ultrasound at GW 32 + 2 showed a normal foetal weight deviation of +8%1 .
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| 46. |
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| 47. |
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| 48. |
- Abbott, Jessica K., et al.
(författare)
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Sex chromosome evolution : Historical insights and future perspectives
- 2017
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1854
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Forskningsöversikt (refereegranskat)abstract
- Many separate-sexed organisms have sex chromosomes controlling sex determination. Sex chromosomes often have reduced recombination, specialized (frequently sex-specific) gene content, dosage compensation and heteromorphic size. Research on sex determination and sex chromosome evolution has increased over the past decade and is today a very active field. However, some areas within the field have not received as much attention as others.We therefore believe that a historic overviewof key findings and empirical discoveries will put current thinking into context and help us better understand where to go next. Here, we present a timeline of important conceptual and analytical models, as well as empirical studies that have advanced the field and changed our understanding of the evolution of sex chromosomes. Finally, we highlight gaps in our knowledge so far and propose some specific areas within the field that we recommend a greater focus on in the future, including the role of ecology in sex chromosome evolution and newmultilocus models of sex chromosome divergence.
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| 49. |
- Abrahamsson, Johanna, 1990, et al.
(författare)
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A Raman spectroscopic approach to investigate the production of biodiesel from soybean oil using 1-alkyl-3-methylimidazolium ionic liquids with intermediate chain length
- 2015
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Ingår i: Applied Energy. - : Elsevier BV. - 1872-9118 .- 0306-2619. ; 154, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- We present a Raman spectroscopic study of the conversion of soybean oil into biodiesel by methanol using the lipase B enzyme pseudomonas cepacia as the bio-catalyst and 1-alkyl-3-methylimidazolium ionic liquids (CnC1Im) as co-solvents, where the alkyl chain length is varied from ethyl (n=2) to decyl (n=10). We have limited this study to a low reaction temperature, 40°C, and a low enzyme concentration to investigate the possibility of producing biodiesel with low energy and cost demands. We also demonstrate that Raman spectroscopy is a powerful and straightforward method to estimate the yield of the transesterification reaction, by analysis of the characteristic CO stretching mode found in the range ~1730-1750cm-1. Our results indicate that both reaction yield and reaction rate increase with the chain length, but also that for chains longer than decyl further improvements are marginal. We discuss these results from the viewpoint of local interactions and local structure of the investigated ionic liquids.
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| 50. |
- Acosta Navarro, Juan C., et al.
(författare)
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Future response of temperature and precipitation to reduced aerosol emissions as compared with increased greenhouse gas concentrations
- 2017
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Ingår i: Journal of Climate. - 0894-8755 .- 1520-0442. ; 30:3, s. 939-954
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Tidskriftsartikel (refereegranskat)abstract
- Experiments with a climate model (NorESM1) were performed to isolate the effects of aerosol particles and greenhouse gases on surface temperature and precipitation in simulations of future climate. The simulations show that by 2025-2049, a reduction of aerosol emissions from fossil fuels following a maximum technically feasible reduction (MFR) scenario could lead to a global and Arctic warming of 0.26 K and 0.84 K, respectively; as compared with a simulation with fixed aerosol emissions at the level of 2005. If fossil fuel emissions of aerosols follow a current legislation emissions (CLE) scenario, the NorESM1 model simulations yield a non-significant change in global and Arctic average surface temperature as compared with aerosol emissions fixed at year 2005. The corresponding greenhouse gas effect following the RCP4.5 emission scenario leads to a global and Arctic warming of 0.35 K and 0.94 K, respectively.The model yields a marked annual average northward shift in the inter-tropical convergence zone with decreasing aerosol emissions and subsequent warming of the northern hemisphere. The shift is most pronounced in the MFR scenario but also visible in the CLE scenario. The modeled temperature response to a change in greenhouse gas concentrations is relatively symmetric between the hemispheres and there is no marked shift in the annual average position of the inter-tropical convergence zone. The strong reduction in aerosol emissions in MFR also leads to a net southward cross-hemispheric energy transport anomaly both in the atmosphere and ocean, and enhanced monsoon circulation in Southeast and East Asia causing an increase in precipitation over a large part of this region.
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