| 1. |
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Eskelund, Christian W., et al.
(författare)
-
15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
- 2016
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
-
Tidskriftsartikel (refereegranskat)abstract
- In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
|
|
| 4. |
- Jung, Christian, et al.
(författare)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
|
|
| 5. |
- van Rheenen, Wouter, et al.
(författare)
-
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
-
Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
|
|
| 6. |
- Brønd, Jan Christian, et al.
(författare)
-
The ActiGraph counts processing and the assessment of vigorous activity.
- 2019
-
Ingår i: Clinical physiology and functional imaging. - : Wiley. - 1475-097X .- 1475-0961. ; 39:4, s. 276-283
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the effect of different band-pass filters on the measurement bias with ActiGraph counts during high speed running and for estimating free-living vigorous physical activity (VPA). Two alternative band-pass filters were designed, extending the original frequency range from 0·29 to 1·66Hz (AG) to 0·29-4Hz (AC4) and 0·29-10Hz (AC10). Sixty-two subjects in three age groups participated in a structured locomotion protocol consisting of multiple walking and running speeds. The time spent in free-living VPA using the three different band-pass filters were evaluated in 1121 children. Band-pass filter specific intensity cut-points from both linear regression and ROC analysis was identified from a calibration experiment using indirect calorimetry. The ActiGraph GT3X+ device recording raw acceleration at 30Hz was used in all experiments. The linear association between counts and running speed was negative for AG but positive for AC4 and AC10 across all age groups. The time spent in free-living VPA was similar for all band-pass filters. Considering higher frequency information in the generation of ActiGraph counts with a hip/waist worn device reduces the measurement bias with running above 10km·h-1 . However, additional developments are required to accurately capture all VPA, including intermittent activities.
|
|
| 7. |
- Eskelund, Christian W., et al.
(författare)
-
TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
- 2017
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
-
Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
|
|
| 8. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 9. |
|
|
| 10. |
- Kolstad, Arne, et al.
(författare)
-
Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years
- 2017
-
Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 23:3, s. 428-435
-
Tidskriftsartikel (refereegranskat)abstract
- The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P <.0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P <.0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.
|
|
| 11. |
- Wang, Haidong, et al.
(författare)
-
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Ahmed, Niaz, et al.
(författare)
-
Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.
- 2019
-
Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 4:4, s. 307-317
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
|
|
| 16. |
- Almqvist, Gustaf, et al.
(författare)
-
Report of the Benchmark Workshop on Baltic Cod Stocks (WKBALTCOD)
- 2015
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The ICES Benchmark Workshop on Baltic Cod Stocks (WKBALTCOD), chaired by External Chair Jean-Jacques Maguire, Canada and ICES Chair Marie Storr-Paulsen, Denmark, and attended by two invited external experts Verena Trenkel, France and Meaghan Bryan, USA met in Rostock, Germany, 2–6 March 2015 with 39 participants and six countries represented. The objective of WKBALTCOD was to evaluate the appropriateness of data and methods to determine stock status and investigate meth-ods appropriate to use in the single-stock assessment for the cod stock in SD 22–24 and cod in SD 25–32 in the Baltic. Participants in the workshop were a large group with diverse backgrounds representing the industry, fisheries, NGOs, managers and scientists.The single-stock analytic assessment of the eastern Baltic stock was not accepted by the assessment working group (WGBFAS) in 2014 due to severe problems with the input data. The advice for the eastern Baltic cod was, therefore, based on the ICES approach for data-limited stocks. As an outcome ICES decided to establish a bench-mark for both cod stocks and to scope an integrated assessment for the Baltic cod stocks. The first meeting (WKSIBCA) was therefore meant to introduce the interces-sional work conducted since the assessment working group in April 2014, and to reach some conclusions on how to proceed both in the short term (Benchmark in March 2015) and longer term (2–3 years) and was seen as a data compilation work-shop, there is produced a separate report from this workshop. The WKBALTCOD was the 2nd meeting in the benchmark process and was intended to come up with a final stock assessment method, stock annex and input data for both stocks. As it was not possible to reach conclusive decision on the final model to be used for the east Baltic cod stock during the benchmark meeting and as more work on the preferable models was needed, it was decided by the ACOM leadership to prolong the bench-mark process until the assessment working group meeting in April 2015. This deci-sion has led to a relatively long process partly mixed with the assessment working group WGBFAS.It became clear during the benchmark process that although large effort has been put into explaining the underlying processes leading to the changes in the Baltic ecosys-tem, there is still some lack of understanding of the present situation in the eastern Baltic cod stock. Therefore, it was not possible to reach firm conclusions on the final model to be used and therefore not possible to set reference points. It was decided to continue to explore the most promising models and to continue to improve the input data until the assessment working group started in April.The main challenges still to be solved for the Eastern Baltic cod stock is the quantifi-cation of increased natural mortality and decrease in growth. Through several presentations during the workshop (both WKSIBCA and WKBALTCOD) it became clear that natural mortality very likely has increased in later years, due to decreased condition and increased parasite infection. A decrease in growth also seems plausible duo to a decrease in condition and/or selectivity-induced mortality of the largest in-dividuals. However, as none of these parameters are easily estimated, especially with the severe ageing problems, different model assumptions made the output very shaky.For the western Baltic cod, stock identification issues were examined in area SD 24, the intermediate area: based on otolith characteristics and genetics. Due to the results showing a large proportion of east cod in this area, it was decided to split the catch2 | ICES WKBALTCOD REPORT 2015and survey from SD 24 into either the western or eastern Baltic cod stock. It was pos-sible to derive proportions of eastern and western cod in SD 24 back to the mid-1990s.For the western Baltic cod stock a modelled survey indices was included in the as-sessment covering the western part of SD 24 and Area 22+23 and based on a smoothed ALK.Both cod stocks have in the past used commercial tuning fleet to have a better cov-ered of older age groups. It was decided to abound this time-series duo quality issues such as a limited coverage and problems with technical creeping.WKBALTCOD was not able to explore and define reference points for the Western Baltic cod stock during the meeting due to time constraints, but these were calculated and decided by correspondence after the meeting. The recent protocols on estimation procedures developed by WKMSYREF3 for stocks with a full analytical assessment and for data-limited stocks served as objective guidelines to obtain reference point estimates.
|
|
| 17. |
- Alvarez, Beatriz, et al.
(författare)
-
An Exopolysaccharide-Deficient Mutant of Lactobacillus rhamnosus GG Efficiently Displays a Protective Llama Antibody Fragment against Rotavirus on Its Surface
- 2015
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 81:17, s. 5784-5793
-
Tidskriftsartikel (refereegranskat)abstract
- Rotavirus is the leading cause of infantile diarrhea in developing countries, where it causes a high number of deaths among infants. Two vaccines are available, being highly effective in developed countries although markedly less efficient in developing countries. As a complementary treatment to the vaccines, a Lactobacillus strain producing an anti-rotavirus antibody fragment in the gastrointestinal tract could potentially be used. In order to develop such an alternative therapy, the effectiveness of Lactobacillus rhamnosus GG to produce and display a VHH antibody fragment (referred to as anti-rotavirus protein 1 [ARP1]) on the surface was investigated. L. rhamnosus GG is one of the best-characterized probiotic bacteria and has intrinsic antirotavirus activity. Among four L. rhamnosus GG strains [GG (CMC), GG (ATCC 53103), GG (NCC 3003), and GG (UT)] originating from different sources, only GG (UT) was able to display ARP1 on the bacterial surface. The genomic analysis of strain GG (UT) showed that the genes welE and welF of the EPS cluster are inactivated, which causes a defect in exopolysaccharide (EPS) production, allowing efficient display of ARP1 on its surface. Finally, GG (UT) seemed to confer a level of protection against rotavirus-induced diarrhea similar to that of wild-type GG (NCC 3003) in a mouse pup model, indicating that the EPS may not be involved in the intrinsic antirotavirus activity. Most important, GG (EM233), a derivative of GG (UT) producing ARP1, was significantly more protective than the control strain L. casei BL23.
|
|
| 18. |
- Andersen, Christina, et al.
(författare)
-
Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
- 2018
-
Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
-
Konferensbidrag (refereegranskat)abstract
- We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
|
|
| 19. |
- Andersen, Christina, et al.
(författare)
-
Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study
- 2018
-
Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800
-
Tidskriftsartikel (refereegranskat)abstract
- Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Andersen, Jeppe R., et al.
(författare)
-
Les Houches 2017: Physics at TeV Colliders Standard Model Working Group Report
- 2018. - 07977
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This Report summarizes the proceedings of the 2017 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt with (I) new developments relevant for high precision Standard Model calculations, (II) theoretical uncertainties and dataset dependence of parton distribution functions, (III) new developments in jet substructure techniques, (IV) issues in the theoretical description of the production of Standard Model Higgs bosons and how to relate experimental measurements, (V) phenomenological studies essential for comparing LHC data from Run II with theoretical predictions and projections for future measurements, and (VI) new developments in Monte Carlo event generators.
|
|
| 24. |
|
|
| 25. |
- Andersén, Jim, 1976-, et al.
(författare)
-
Resource immobility and sustained performance : A systematic assessment of how immobility has been considered in empirical resource-based studies
- 2016
-
Ingår i: International journal of management reviews (Print). - : John Wiley & Sons. - 1460-8545 .- 1468-2370. ; 18:4, s. 371-396
-
Tidskriftsartikel (refereegranskat)abstract
- The core notion of the resource-based view (RBV) is that the possession of certain resources can result in superior performance and, in order for this performance to be sustained, these resources cannot be perfectly mobile. Whereas previous reviews have mainly focused on the relationship between resources and temporary performance, no studies have systematically analyzed the extent to which empirical RBV studies have specifically considered immobility of resources. By analyzing a sample of 218 empirical RBV studies, the authors found that 17% of the studies directly measured some dimension of immobility (by, for example, actually measuring the level of social complexity, unique history, tacitness or tradability). Fewer than 2% of the studies measured the outcome of resource immobility, i.e. sustained performance differences. Based on these results, this paper discusses the consequences of overlooking this key dimension of the RBV (i.e. immobility) and suggests that, and discusses how, future research should consider resource immobility to a greater extent.
|
|
| 26. |
- Andersen, Thomas Barnebeck, et al.
(författare)
-
The heavy plow and the agricultural revolution in Medieval Europe
- 2016
-
Ingår i: Journal of Development Economics. - : Elsevier. - 0304-3878 .- 1872-6089. ; 118, s. 133-149
-
Tidskriftsartikel (refereegranskat)abstract
- This research sheds new light on the much-debated link between agricultural productivity and development. We do so by estimating the causal impact of a large shock to agricultural productivity—the introduction of the heavy plow in the Middle Ages—on long run development. We build on the work of Lynn White, Jr. (1962), who argued that it was impossible to take proper advantage of the fertile clay soils of Northern Europe prior to the invention and widespread adoption of the heavy plow. We implement the test in a difference-in-difference set-up by exploiting regional variation in the presence of fertile clay soils. Using a high quality dataset for Denmark, we find that historical counties with relatively more fertile clay soil experienced higher urbanization after the heavy plow had its breakthrough, which was around AD 1000. We obtain a similar result, when we extend the test to European regions. Our findings substantiate that agricultural productivity can be an important driver of long-run development.
|
|
| 27. |
- Andersén, Åsa, 1975-, et al.
(författare)
-
Positive experiences of a vocational rehabilitation intervention for individuals on long-term sick leave, the Dirigo project : a qualitative study
- 2017
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The process of returning to work after long-term sick leave can sometimes be complex. Many factors, (e.g. cooperation between different authorities and the individual as well as individual factors such as health, emotional well-being and self-efficacy) may have an impact on an individual’s ability to work. The aim of this study was to investigate clients’ experiences with an individually tailored vocational rehabilitation, the Dirigo project, and encounters with professionals working on it. The Dirigo project was based on collaboration between rehabilitation authorities, individually tailored interventions and a motivational interviewing approach. Methods: A descriptive qualitative design was used with data collected through interviews. Fourteen individuals on long-term sick leave took part in individual semi-structured interviews. The interviews were analysed using content analysis.Results: The analysis showed overall positive experience of methods and encounters with professionals in a vocational rehabilitation project. The positive experiences were based on four key factors: 1. Opportunities for receiving various dimensions of support. 2. Good overall treatment by the professionals. 3. Satisfaction with the working methods of the project, and 4. Opportunities for personal development.Conclusions: The main result showed that the clients had an overall positive experience of a vocational rehabilitation project and encounters with professionals who used motivational interviewing as a communication method. The overall positive experience indicated that their interactions with the different professionals may have affected their self-efficacy in general and in relation to transition to work. The knowledge is essential for the professionals working in the area of vocational rehabilitation. However, vocational rehabilitation interventions also need a societal approach to be able to offer clients opportunities for job training and real jobs.
|
|
| 28. |
- Andersson, Tilde, et al.
(författare)
-
Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Cutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes's secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.
|
|
| 29. |
- Arvidsson, Daniel, 1974, et al.
(författare)
-
Re-examination of accelerometer data processing and calibration for the assessment of physical activity intensity.
- 2019
-
Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 29:10, s. 1442-1452
-
Tidskriftsartikel (refereegranskat)abstract
- This review reexamines use of accelerometer and oxygen uptake data for assessment of activity intensity. Accelerometers capture mechanical work, while oxygen uptake captures the energy cost of this work. Frequency filtering needs to be considered when processing acceleration data. A too restrictive filter attenuates the acceleration signal for walking and, to a higher degree, for running. This measurement error affects shorter (children) more than taller (adults) individuals due to their higher movement frequency. Less restrictive filtering includes more movement related signals and provide measures that better capture mechanical work, but may include more noise. An optimal filter cut-point is determined where most relevant acceleration signals are included. Further, accelerometer placement affects what part of mechanical work being captured. While the waist placement captures total mechanical work and therefore contributes to measures of activity intensity equivalent by age and stature, the thigh and wrist placements capture more internal work and do not provide equivalent measures. Value calibration of accelerometer measures is usually performed using measured oxygen uptake with the metabolic equivalent of task (MET) as reference measure of activity intensity. However, the use of MET is not stringent and is not a measure of activity intensity equivalent by age and stature. A candidate measure is the mass-specific net oxygen uptake, VO2 net (VO2 tot - VO2 stand). To improve measurement of physical activity intensity using accelerometers, research developments are suggested concerning processing of accelerometer data, use of energy expenditure as reference for activity intensity, and calibration procedure with absolute versus relative intensity. This article is protected by copyright. All rights reserved.
|
|
| 30. |
- Auer-Grumbach, Michaela, et al.
(författare)
-
Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies
- 2016
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:3, s. 607-623
-
Tidskriftsartikel (refereegranskat)abstract
- Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade beta-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.
|
|
| 31. |
- Beelen, Rob, et al.
(författare)
-
Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
-
Forskningsöversikt (refereegranskat)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
|
|
| 32. |
- Brenner, David, et al.
(författare)
-
Hot-spot KIF5A mutations cause familial ALS
- 2018
-
Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 688-697
-
Tidskriftsartikel (refereegranskat)abstract
- Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10-3), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10-7). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
|
|
| 33. |
|
|
| 34. |
- Brinck, Ingar, et al.
(författare)
-
Making Place for Social Norms in the Design of Human-Robot Interaction
- 2016
-
Ingår i: What Social Robots Can and Should Do : Proceedings of RoboPhilosophy 2016/TRANSOR 2016 - Proceedings of RoboPhilosophy 2016/TRANSOR 2016. - 9781614997085 - 9781614997078 ; 290, s. 303-312
-
Bokkapitel (refereegranskat)abstract
- We argue that social robots should be designed to behave similarly to humans, and furthermore that social norms constitute the core of human interaction. Whether robots can be designed to behave in human-like ways turns on whether they can be designed to organize and coordinate their behavior with others’ social expectations. We suggest that social norms regulate interaction in real time, whereagents relies on dynamic information about their own and others’ attention, intention and emotion to perform social tasks.
|
|
| 35. |
- Brønd, Jan Christian, et al.
(författare)
-
Generating ActiGraph Counts from Raw Acceleration Recorded by an Alternative Monitor
- 2017
-
Ingår i: Medicine and Science in Sports and Exercise. - 0195-9131. ; 49:11, s. 2351-2360
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To implement an aggregation method in Matlab for generating ActiGraph counts from raw acceleration recorded with an alternative accelerometer device and to investigate the validity of the method. METHODS: The aggregation method including the frequency band-pass filter was implemented and optimized based on standardized sinusoidal acceleration signals generated in Matlab and processed in the ActiLife software. Evaluating the validity of the aggregation method was approached using a mechanical setup and with a 24-hour free-living recording using a convenient sample of nine subjects. Counts generated with the aggregation method applied to Axivity AX3 raw acceleration data were compared to counts generated with ActiLife from ActiGraph GT3X+ data. RESULTS: An optimal band-pass filter was fitted resulting in a root mean squared error (RMSE) of 25.7 counts per 10 second and mean absolute error (MAE) of 15.0 counts per second across the full frequency range. The mechanical evaluation of the proposed aggregation method resulted in an absolute mean (sd) difference of -0.11 (0.97) counts per 10 second across all rotational frequencies compared to the original ActiGraph method. Applying the aggregation method to the 24-hour free-living recordings resulted in an epoch level bias ranging from -16.2 to 0.9 counts per 10 second, a relative difference in the averaged physical activity (counts per minute) ranging from -0.5% to 4.7% with a group mean (sd) of 2.2% (1.7%) and a Cohen’s Kappa of 0.945 indicating almost a perfect agreement in the intensity classification. CONCLUSION: The proposed band-pass filter and aggregation method is highly valid for generating ActiGraph counts from raw acceleration data recorded with alternative devices. It would facilitate comparability between studies using different devices collecting raw acceleration data.
|
|
| 36. |
- Burkhardt, Christian, et al.
(författare)
-
Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? : A post-mortem study of 80 ALS patients
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown.Objective: To investigate the effect of NIV and PEG on survival and causes of death in ALS patients.Methods: Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Forty-two of these patients consented for genetic testing. Effects of NIV and PEG on survival and causes of death were analyzed in a multivariable Cox proportional hazard regression.Results: Six patients, who requested assisted suicide causing drug-induced hypoxia, were excluded from final analysis. Respiratory failure was the main cause of death in 72 out of 74 patients. Fifteen out of 74 died of aspiration pneumonia 23/74 of bronchopneumonia and 8/74 of a combination of aspiration pneumonia and bronchopneumonia. Twenty died of hypoxia without concomitant infection, and six patients had pulmonary embolism alone or in combination with pneumonia. NIV (p = 0.01) and PEG (p<0.01) had a significant impact on survival. In patients using NIV bronchopneumonia was significantly more frequent (p <0.04) compared to non-NIV patients. This effect was even more pronounced in limb onset patients (p<0.002). Patients with C9orf72 hexanucleotide repeat expansions showed faster disease progression and shorter survival (p = 0.01).Conclusion: The use of NIV and PEG prolongs survival in ALS. This study supports current AAN and EFNS guidelines which recommend NIV and PEG as a treatment option in ALS. The risk of bronchopneumonia as cause of death may be increased by NIV.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Gommenginger, Christine, et al.
(författare)
-
SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas
- 2019
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
|
|
| 40. |
- Goncalves, Nadia P., et al.
(författare)
-
Peripheral Nerve Regeneration Is Independent From Schwann Cell p75(NTR) Expression
- 2019
-
Ingår i: Frontiers in Cellular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5102. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75(NTR) has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75(NTR) knockout mouse models and cannot dissect the specific role of p75(NTR) expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75(NTR) expression in Schwann cells was generated, where p75(NTR) expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75(NTR) expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75(NTR). No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75(NTR) reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75(NTR) expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75(NTR) in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75(NTR) in remyelination most likely depending on axonal/neuronal p75(NTR) and/or mutual glial-axonal interactions.
|
|
| 41. |
- Guidet, Bertrand, et al.
(författare)
-
Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit
- 2018
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:7, s. 1027-1038
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU.METHODS: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up.RESULTS: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries.CONCLUSIONS: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country.TRIAL REGISTRATION: ClinicalTrials.gov (ID: NTC03134807).
|
|
| 42. |
- Gustafsen, Camilla, et al.
(författare)
-
Heparan sulfate proteoglycans present PCSK9 to the LDL receptor
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9: LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.
|
|
| 43. |
- Hansen, Benni W., et al.
(författare)
-
In situ and experimental evidence for effects of elevated pH on protistan and metazoan grazers
- 2019
-
Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 41:3, s. 257-271
-
Tidskriftsartikel (refereegranskat)abstract
- Plankton succession was studied in a hyper-eutrophic stratified estuary, Mariager Fjord, Denmark. Above the pycnocline (15 m) pH increased from 8.5 to 9.2 and the oxygen increased to super saturation after 5 d of sunny weather due to high primary production. The protistan grazers were dominated by heterotrophic dinoflagellates and mixotrophic and heterotrophic ciliates. Metazooplankton was dominated by meroplankton, rotifers and the copepod, Acartia tonsa, all with a relatively low biomass. Cirriped nauplii occupied the upper strata while polychaete larvae populated the whole water column. Bivalve larvae occurred occasionally above the pycnocline even at very high pH. In pH challenge experiments, the mixotrophic ciliate Mesodinium rubrum was the least pH tolerant species, followed by Strombidium spp., which did not cope well with seawater pH > 8.5. Some heterotrophic dinoflagellates were more tolerant with net growth at pH > 9. The predominant rotifer Synchaeta sp. tolerated up to pH 9.5 and the copepod survived pH 10 but stopped producing eggs at pH 9.5 with unaffected egg hatching success. The polychaete and cirriped larvae tolerated pH 9.5, but bivalve larvae showed decreased survival already at pH 8.5. In situ distribution patterns and pH challenge experiments suggest that pH indeed contribute to structuring zooplankton distribution.
|
|
| 44. |
- Hedengran, Katrine K., et al.
(författare)
-
Environmental tobacco smoke exposure during pregnancy has limited effect on infant birthweight and umbilical vein endothelial nitric oxide synthase
- 2018
-
Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:11, s. 1309-1316
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Women who smoke, deliver significantly smaller infants. These infants have reduced levels of the vasodilator endothelial nitric oxide synthase (eNOS) levels in the umbilical vessels, which may reduce fetal growth. Serum cotinine, the degradation product of nicotine, can be used to determine the level of tobacco exposure. Newborns of environmental smokers are suggested to be smaller and shorter in weight, length, and head circumference. eNOS levels have not yet been studied in these infants. We here investigated the existence of a relation between maternal environmental tobacco smoke exposure, eNOS activity, concentration, and birthweight. Material and methods: We included 263 healthy singleton pregnancies categorized into three groups according to measured cotinine levels: 175 nonsmokers, 38 smokers, and 50 environmental smokers. Cotinine was quantified by mass spectrometry with a detection limit of.2 ng/mL; eNOS activity and concentration were measured in endothelial cells (ECs) of the umbilical vein. Results: Infants born to environmental smokers had similar weights to infants born to nonsmokers (47 g heavier, P =.48). Cotinine concentrations were.06/.09/.12 ng/mL (quartiles) in infants born to nonsmokers,.27/.37/.81 ng/mL in infants born to women exposed to environmental tobacco smoke, and 43.0/63.8/108.1 ng/mL in infants born to smokers. The eNOS concentration was 1.65 ±.92 ng/106 ECs (mean ± SD) in nonsmokers and 1.71 ± 1.00 ng/106 ECs in environmental smokers. The eNOS activity was 52.0 ± 20.6 pmol l-citrulline/min/106 ECs in nonsmokers and 48.7 ± 19.8 pmol l-citrulline/min/106 ECs in environmental smokers. Conclusions: Infants born to environmental smokers, as judged by umbilical serum cotinine levels close to.2 ng/mL, are not associated with lower birthweight or reduced eNOS activity, or concentration in the fetal vascular bed.
|
|
| 45. |
- Heggheim, Siri Elise, et al.
(författare)
-
AIS ANALYSIS OF IDLE TIME IN DIFFERENT SCANDINAVIAN OIL REFINERY PORT AREA
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A ship’s productivity is measured by the number of loaded days at sea. Time in ballast, time off hire and port time are the three main factors that influence productivity. Since the tanker segment has limited possibilities for backhauls, it is common that time in ballast accounts for about 50% of their annual voyages. Time off hire depend on the time spent on essentials as repair and surveys, and of course conditions in the freight market. The overall shipping industry suffers from a continuous imbalance of supply and demand (Stopford, 2009). The last couple of years has been challenging, as new external factors makes demand less predictable (Bellemare, 2017). For the tanker industry, 2015 was probably the best year since the market crisis in 2008 (UNCTAD, 2016, p. 57). However, in 2016, the fortune faded (BIMCO, 2017). Time use at port is the last factor to influence productivity. As an element that is to some extent controllable, port time is a central and widely discussed topic. The functions of a port are crucial for a ship’s productivity. Especially since port charges are a major part of a ship’s voyage cost (Stopford, 2009). As a part of the Interreg project - NØKS II (Nærskipsfart i Øresund / Kattegat/Skagerrak), this research addresses the topic of port time. NØKS II focuses on facilitation and development of sea transportation in a specified area. The aim is to evolve an attractive, environmental, safe and sustainable freight flow between Norway, Sweden and Denmark (Vestfold Fylkeskommune, 2015). This study has been conducted based upon analysis of AIS-data from the year 2016. The total amount of time the vessel that arrived or departed from the selected ports are measured and classified as active or idle time. The majority of the idle time is when the vessel is entering the anchorage area which means that the idle time occurs under an “inward voyage”. The fact is that more than two vessels are often calling to a refinery at the same time, thus the build-up starts. Every ship owner or charter want as many sailing days pr. ship since this when they are making their money, not when the ship is at anchor, also known as idle time. The paper presents the extent of idle time in oil ports by the use of AIS data. The study is performed on two ports, one in Sweden and one I Norway. The paper presents a comperative study between ports in Norway and Sweden. In Sweden the choice of port landed on Brofjorden, an oil port owned by the largest fuel company in Sweden, Preem AB (Preem AB, 2017). In Norway Slagentangen refinery owned by Norwegian Esso was selected.
|
|
| 46. |
- Jelenkovic, Aline, et al.
(författare)
-
Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
-
Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
|
|
| 47. |
- Krais, Annette M., et al.
(författare)
-
Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure
- 2018
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 15:11
-
Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100⁻300 µg/m³ of deuterium-labelled diethyl phthalate (D₄-DEP) and bis(2-ethylhexyl) phthalate (D₄-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D₄-DEP and D₄-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D₄-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m³ (nmol of urinary metabolites per phthalates air concentration in (nmol/m³)). After dermal exposure to D₄-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m³. After combined inhalation and dermal exposure to D₄-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m³ between participants. No dermal uptake of particle phase D₄-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D₄-DEP was three times higher than after combined exposure to D₄-DEHP; and nine times higher than after dermal exposure of D₄-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.
|
|
| 48. |
|
|
| 49. |
- Lopez, A. Garcia, et al.
(författare)
-
Validation of SenseWear Armband in children, adolescents, and adults
- 2018
-
Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 28:2, s. 487-495
-
Tidskriftsartikel (refereegranskat)abstract
- SenseWear Armband (SW) is a multisensor monitor to assess physical activity and energy expenditure. Its prediction algorithms have been updated periodically. The aim was to validate SW in children, adolescents, and adults. The most recent SW algorithm 5.2 (SW5.2) and the previous version 2.2 (SW2.2) were evaluated for estimation of energy expenditure during semi-structured activities in 35 children, 31 adolescents, and 36 adults with indirect calorimetry as reference. Energy expenditure estimated from waist-worn ActiGraph GT3X+ data (AG) was used for comparison. Improvements in measurement errors were demonstrated with SW5.2 compared to SW2.2, especially in children and for biking. The overall mean absolute percent error with SW5.2 was 24% in children, 23% in adolescents, and 20% in adults. The error was larger for sitting and standing (23%-32%) and for basketball and biking (19%-35%), compared to walking and running (8%-20%). The overall mean absolute error with AG was 28% in children, 22% in adolescents, and 28% in adults. The absolute percent error for biking was 32%-74% with AG. In general, SW and AG underestimated energy expenditure. However, both methods demonstrated a proportional bias, with increasing underestimation for increasing energy expenditure level, in addition to the large individual error. SW provides measures of energy expenditure level with similar accuracy in children, adolescents, and adults with the improvements in the updated algorithms. Although SW captures biking better than AG, these methods share remaining measurements errors requiring further improvements for accurate measures of physical activity and energy expenditure in clinical and epidemiological research.
|
|
| 50. |
- Lund, Lars, et al.
(författare)
-
Use of venous-thrombotic-embolic prophylaxis in patients undergoing surgery for renal tumors : a questionnaire survey in the Nordic countries (The NORENCA-2 study)
- 2018
-
Ingår i: Research and Reports in Urology. - : DOVE Medical Press Ltd.. - 2253-2447. ; 10, s. 181-187
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery.Materials and methods: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities.Results: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate.Conclusion: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery.
|
|
