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1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
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.	Aslam, Tayyba N., et al. (författare) A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure 2023 Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394 Tidskriftsartikel (refereegranskat)abstract BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
7.	Bjerregaard-Andersen, Morten, et al. (författare) Tuberculosis burden in an urban population: a cross sectional tuberculosis survey from Guinea Bissau 2010 Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 10 Tidskriftsartikel (refereegranskat)abstract Background: Little is known about the prevalence of pulmonary tuberculosis (TB) in low income countries. We conducted a cross sectional survey for pulmonary TB and TB symptoms in Bissau, Guinea-Bissau, in an urban cohort with known HIV prevalence. TB surveillance in the area is routinely based on passive case finding. Methods: Two cohorts were selected based on a previous HIV survey, but only 52.5% of those enrolled in the adult cohort had participated in the HIV survey. One cohort included all adults living in 384 randomly selected houses; in this cohort 8% (135/1687) were HIV infected. The other included individuals 50 years or older from all other houses in the study area; of these 11% (62/571) were HIV infected. Symptom screening was done through household visits using a standardised questionnaire. TB suspects were investigated with sputum smear microscopy and X-ray. Results: In the adult cohort, we found 4 cases among 2989 individuals screened, giving a total TB prevalence of 134/100,000 (95% CI 36-342/100,000). In the >50 years cohort, we found 4 cases among 571 individuals screened, giving a total prevalence of 701/100,000 (191-1784/100.000). Two of the eight detected TB cases were unknown by the TB program. Of the total TB cases five were HIV uninfected while three had unknown HIV status. The prevalence of TB symptoms was 2.1% (63/2989) and 10.3% (59/571) in the two cohorts respectively. Conclusions: In conclusion we found a moderately high prevalence of pulmonary TB and TB symptoms in the general population, higher among elderly individuals. By active case finding unknown cases were detected. Better awareness of TB and its symptoms needs to be promoted in low income settings.
8.	Breznau, Nate, et al. (författare) Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty 2022 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44 Tidskriftsartikel (refereegranskat)abstract This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
9.	Brieghel, Christian, et al. (författare) The Number of Signaling Pathways Altered by Driver Mutations in Chronic Lymphocytic Leukemia Impacts Disease Outcome 2020 Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:6, s. 1507-1515 Tidskriftsartikel (refereegranskat)abstract Purpose: Investigation of signaling pathways altered by recurrent gene mutations and their clinical impact in a consecutive cohort of patients with newly diagnosed chronic lymphocytic leukemia (CLL). The heterogeneous clinical course and genetic complexity of CLL warrant improved molecular prognostication. However, the prognostic value of recurrent mutations at the time of diagnosis remains unclear. Experimental Design: We sequenced samples from 314 consecutive, newly diagnosed patients with CLL to investigate the clinical impact of 56 recurrently mutated genes assessed by next-generation sequencing. Results: Mutations were identified in 70% of patients with enrichment among IGHV unmutated cases. With 6.5 years of follow-up, 15 mutated genes investigated at the time of diagnosis demonstrated significant impact on time to first treatment (TTFT). Carrying driver mutations was associated with shorter TTFT and poor overall survival. For outcome from CLL diagnosis, the number of signaling pathways altered by driver mutations stratified patients better than the number of driver mutations. Moreover, we demonstrated gradual impact on TTFT with increasing number of altered pathways independent of CLL-IPI risk. Thus, a 25-gene, pathway-based biomarker assessing recurrent mutations refines prognostication in CLL, in particular for CLL-IPI low- and intermediate-risk patients. External validation emphasized that a broad gene panel including low burden mutations was key for the biomarker based on altered pathways. Conclusions: We propose to include the number of pathways altered by driver mutations as a biomarker together with CLL-IPI in prospective studies of CLL from time of diagnosis for incorporation into clinical care and personalized follow-up and treatment.
10.	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.
11.	Christensen, Christian Kolle, et al. (författare) Beam damage in operando X-ray diffraction studies of Li-ion batteries 2023 Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 30:Pt 3, s. 561-570 Tidskriftsartikel (refereegranskat)abstract Operando powder X-ray diffraction (PXRD) is a widely employed method for the investigation of structural evolution and phase transitions in electrodes for rechargeable batteries. Due to the advantages of high brilliance and high X-ray energies, the experiments are often carried out at synchrotron facilities. It is known that the X-ray exposure can cause beam damage in the battery cell, resulting in hindrance of the electrochemical reaction. This study investigates the extent of X-ray beam damage during operando PXRD synchrotron experiments on battery materials with varying X-ray energies, amount of X-ray exposure and battery cell chemistries. Battery cells were exposed to 15, 25 or 35 keV X-rays (with varying dose) during charge or discharge in a battery test cell specially designed for operando experiments. The observed beam damage was probed by μPXRD mapping of the electrodes recovered from the operando battery cell after charge/discharge. The investigation reveals that the beam damage depends strongly on both the X-ray energy and the amount of exposure, and that it also depends strongly on the cell chemistry, i.e. the chemical composition of the electrode.
12.	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.
13.	Granholm, Anders, et al. (författare) Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial : Protocol Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. Tidskriftsartikel (refereegranskat)abstract Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
14.	Gylling, Anne Theil, et al. (författare) The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults 2020 Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 136 Tidskriftsartikel (refereegranskat)abstract Background: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals.Methods: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, approximate to 80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed.Findings: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training.Interpretation: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good compliance and induces consistent changes in physiological parameters of muscle strength, muscle mass and abdominal fat.
15.	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.
16.	Jespersen, Sanne, et al. (författare) Differential effects of sex in a West African cohort of HIV-1, HIV-2, and HIV-1/2 infected patients: Men are worse off. 2016 Ingår i: Tropical Medicine & International Health. - : Wiley. - 1365-3156 .- 1360-2276. ; 21:2, s. 253-262 Tidskriftsartikel (refereegranskat)abstract Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and dually infected patients.
17.	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.
18.	Munch, Marie W., et al. (författare) Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial 2021 Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817 Tidskriftsartikel (refereegranskat)abstract Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
19.	Schunkert, Heribert, et al. (författare) Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease 2011 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333 Tidskriftsartikel (refereegranskat)abstract We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
20.	Sinding, Mikkel-Holger S., et al. (författare) Arctic-adapted dogs emerged at the Pleistocene-Holocene transition 2020 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 368:6498 Tidskriftsartikel (refereegranskat)abstract Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an similar to 9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an similar to 33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
21.	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.
22.	Abele, H., et al. (författare) Particle physics at the European Spallation Source 2023 Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84 Forskningsöversikt (refereegranskat)abstract Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
23.	Ahmad, T, et al. (författare) Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries 2016 Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 117:5, s. 601- Tidskriftsartikel (refereegranskat)
24.	Ahmad, T, et al. (författare) In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study 2017 Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 43:12, s. 2324-2332 Tidskriftsartikel (refereegranskat)
25.	Ahmad, T, et al. (författare) Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery 2017 Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 119:2, s. 258-266 Tidskriftsartikel (refereegranskat)
26.	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.
27.	Akimoto, Chizuru, et al. (författare) A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories 2014 Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:6, s. 419-424 Tidskriftsartikel (refereegranskat)abstract Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.
28.	Alayash, Abdu I., et al. (författare) Haptoglobin: the hemoglobin detoxifier in plasma 2013 Ingår i: Trends in Biotechnology. - : Elsevier BV. - 0167-7799. ; 31:1, s. 2-3 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Hemoglobin (Hb) is one of the most studied proteins. However, oxidative toxicity associated with free Hb in circulation and its contribution to inflammation and complications of transfusion have only recently become active areas of research. New insights into the protective mechanisms of haptoglobin (Hp), a plasma protein, and a timely resolution of the crystal structure of the Hb-Hp complex made it possible to definitively link the functional and structural interplay between the two proteins. Here, we summarize current knowledge of the interactions between Hb and Hp under oxidative stress conditions, and how Hb's own damaging radicals are harnessed by complex formation. Potential therapeutic benefits of using Hp for inactivation and clearance of free Hb under a number of clinical settings are considered.
29.	Allentoft, Morten E., et al. (författare) 100 ancient genomes show repeated population turnovers in Neolithic Denmark 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337 Tidskriftsartikel (refereegranskat)abstract Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
30.	Allentoft, Morten E., et al. (författare) Population genomics of post-glacial western Eurasia 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311 Tidskriftsartikel (refereegranskat)abstract Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
31.	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.
32.	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.
33.	Andersen, Andreas, et al. (författare) The immunological effect of revaccination with Bacille Calmette-Guerin vaccine at 19 months of age 2013 Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 31:17, s. 2137-2144 Tidskriftsartikel (refereegranskat)abstract Background: Bacille Calmette-Guerin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. Methods: Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-gamma, interleukin (IL)-13, tumor-necrosis-factor (TNF)-alpha, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. Results: Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-gamma (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR = 1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-alpha/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-alpha response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03). Conclusion: BCG revaccination resulted in a strong IFN-gamma response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-alpha and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination. (C) 2013 Elsevier Ltd. All rights reserved.
34.	Andersen, Christian Benjamin (författare) Friend or Foe? Biocontrol interactions of Pythium oligandrum within the potato cropping system 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The potato crop is a valuable but vulnerable food source on a global level. It is under constant pressure from destructive plant diseases such as early and late blight. Traditionally to control these diseases farmers have relied heavily on synthetic fungicide use. It is evident that the use of agrochemicals such as synthetic fungicides can cause unwanted effects on the environment, and human health. Thus, there is a need for a more sustainable approach to control diseases in the potato cropping system. One approach could be to use biological control agents, (BCAs) such as mycoparasitic Pythium species to control the disease. However, to utilize these BCAs in the best way we need to increase our fundamental knowledge about their biology and interactions within potato cropping systems. Therefore, the aim of this thesis is to broaden our fundamental knowledge of the mycoparasitic Pythium species, Pythium oligandrum and Pythium periplocum, and how they differentiate from their phytopathogenic counterparts. Further, the thesis also pinpoints characteristics that determine mycoparasitism in these two Pythiums, and how this relates to their biocontrol abilities, at the molecular level. This was elucidated using comparative genomics, transcriptomics. The result showed that ABC transporters, AVH-like RXLR effectors, and an expanded CAZyme among other things, are conserved and important for mycoparasitism, by P. oligandrum and P. periplocum both when preying on phytopathogens but also in comparison to closely related plant pathogens. This thesis also explores if P. oligandrum can be used as an antagonist against early blight disease on potato plants. The results showed that P. oligandrum did induce disease suppression in potato in controlled greenhouse environments, however in the field trials when the disease pressure was high the effects disappeared. The thesis also explores if and how P. oligandrum interacts with the potato plants. The results showed that P. oligandrum induced biostimulation in potato both in controlled environments and field studies, although the biostimulation was in a plant-genotype dependent manner. Finally, the thesis investigates the impact on the resident rhizosphere microbiome of field grown potato plants when P. oligandrum was applied. The results showed that P. oligandrum has a very limited impact on the diversity and community structure in the rhizosphere of potato. Overall, the work in this thesis has generated a deeper understanding of the fundamental biology of the mycoparasitic Pythium species and how they differ from plant pathogens. An increased understanding of the environmental consequences and how P. oligandrum can be utilized as a BCA in the potato cropping system has been elucidated. This work also contributes with pivotal knowledge about how P. oligandrum can be utilized in an IPM strategy in the potato agricultural cropping system.
35.	Andersen, Christian B., et al. (författare) Pythium oligandrum induces growth promotion in starch potato without significantly altering the rhizosphere microbiome 2024 Ingår i: Applied Soil Ecology. - 0929-1393. ; 199 Tidskriftsartikel (refereegranskat)abstract Plant health promoting organisms, including microbial biological control agents, are of increasing importance for the development of more sustainable agriculture. To understand the function of these microbes as biological control agents under field conditions and their overall impact on soil and plant health, we need to learn more about the impact of plant beneficial microbes on the rhizosphere microbiome of crops such as potato. The plant beneficial oomycete Pythium oligandrum has previously been reported both as a biocontrol agent and as a plant growth promoter, or biostimulant, in several crop species. To investigate the potential of P. oligandrum as a biostimulant in potato, we performed a series of controlled-environment bioassays in three cultivars. We showed that biostimulation of potato by P. oligandrum is plant genotype-specific. We confirmed the biostimulation by P. oligandrum in the starch potato cultivar Kuras under field conditions. We further investigated the effects of P. oligandrum on the potato rhizosphere microbiome, sampling individual potato plants at three time points over the growing season (representing the vegetative growth phase, flowering, and the onset of senescence). Metabarcoding using ITS and 16S amplicon sequencing revealed no significant overall effect of P. oligandrum application on the bacterial and fungal rhizosphere communities. However, some genera were significantly differentially abundant after P. oligandrum application, including some classified as plant-beneficial microbes. We conclude that P. oligandrum has a cultivar-dependent growth-promoting effect in potato and only minor effects on the rhizosphere microbiome.
36.	Andersen, Christian Benjamin (författare) Transformation systems, gene silencing and gene editing technologies in oomycetes 2022 Ingår i: Fungal Biology Reviews. - : Elsevier BV. - 1749-4613 .- 1878-0253. ; 40, s. 37-52 Forskningsöversikt (refereegranskat)abstract Oomycetes are spore-forming eukaryotic microbes responsible for infections in animal and plant species worldwide, posing a threat to natural ecosystems, biodiversity and food security. Genomics and transcriptomics approaches, together with host interaction studies, give promising results towards better understanding of the infection mechanisms in oomycetes and their general biology. Significant development and progress in oomycetes genomic studies have been achieved over the past decades but further understanding of molecular processes, gene regulations and infection mechanisms are still needed. The use of molecular tools such as CRISPR/Cas and RNAi helped elucidate some of the molecular processes involved in host invasion and infection both in plant and animal pathogenic oomycetes. These methods provide an opportunity for accurate and detailed functional analysis involving various fields of studies such as genomics, epigenomics, proteomics, and interactomics. Functional gene characterisation is essential for filling the knowledge gaps in dynamic biological processes. However, every method has both advantages and limitations that should be considered before choosing the best method for investigating a particular research question. Here we review transformation systems, gene silencing and gene editing techniques in oomycetes, how they function, in which species and what are their main advantages and disadvantages. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of British Mycological Society.
37.	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.
38.	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.
39.	Andersén, Jim, et al. (författare) A Dynamic Approach to Causal Ambiguity : How Organizational Learning Affects Causal Ambiguity 2015 Ingår i: Proceedings of ICICKM 2015 The 12<sup>th</sup> International Conference on Intellectual Capital Knowledge Management and Organisational Learning. - : Academic Conferences and Publishing International Limited. - 9781910810736 Konferensbidrag (refereegranskat)
40.	Andersén, Jim, 1976-, et al. (författare) A Dynamic Approach to Causal Ambiguity - How Organizational Learning Affects Causal Ambiguity 2015 Ingår i: Proceedings of ICICKM 2015 The 12<sup>th</sup> International Conference on Intellectual Capital Knowledge Management and Organisational Learning. - : Academic Conferences and Publishing International Limited. - 9781910810736 Konferensbidrag (refereegranskat)
41.	Andersén, Jim, 1976-, et al. (författare) A model for measuring resource immobility 2014 Konferensbidrag (refereegranskat)
42.	Andersén, Jim, 1976-, et al. (författare) An integrated approach to rent appropriation and rent generation 2016 Konferensbidrag (refereegranskat)
43.	Andersén, Jim, 1976-, et al. (författare) Can environmentally oriented CEOs and environmentally friendly suppliers boost the growth of small firms? 2020 Ingår i: Business Strategy and the Environment. - : John Wiley & Sons. - 0964-4733 .- 1099-0836. ; 29:2, s. 325-334 Tidskriftsartikel (refereegranskat)abstract The core question addressed in the natural resource‐based view (NRBV) of the firm is how to develop and exploit resources beneficial for both the natural environment and firm performance. Due to the resource constraints and increased competition facing small manufacturing firms, achieving this is a challenge for such companies. Building on the NRBV and resource orchestration literatures, we examine the relationship between green purchasing capabilities (GPCs), CEO's environmental orientation(EO), and firm growth. Results from 304 Swedish small manufacturing firms indicate a significant relationship between GPC and growth, and this relationship is positively moderated by the EO of the CEO.
44.	Andersen, Jeppe R., et al. (författare) A Positive Resampler for Monte Carlo events with negative weights 2020 Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:11 Tidskriftsartikel (refereegranskat)abstract We propose the Positive Resampler to solve the problem associated with event samples from state-of-the-art predictions for scattering processes at hadron colliders typically involving a sizeable number of events contributing with negative weight. The proposed method guarantees positive weights for all physical distributions, and a correct description of all observables. A desirable side product of the method is the possibility to reduce the size of event samples produced by General Purpose Event Generators, thus lowering the resource demands for subsequent computing-intensive event processing steps. We demonstrate the viability and efficiency of our approach by considering its application to a next-to-leading order + parton shower merged prediction for the production of a W boson in association with multiple jets.
45.	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.
46.	Andersén, Jim, 1976-, et al. (författare) Rent appropriation management of strategic human capital in practice 2017 Konferensbidrag (refereegranskat)
47.	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.
48.	Andersen, Ken, et al. (författare) B-10 multi-grid proportional gas counters for large area thermal neutron detectors 2013 Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 720, s. 116-121 Tidskriftsartikel (refereegranskat)abstract He-3 was a popular material in neutrons detectors until its availability dropped drastically in 2008. The development of techniques based on alternative convertors is now of high priority for neutron research institutes. Thin films of B-10 or (B4C)-B-10 have been used in gas proportional counters to detect neutrons, but until now, only for small or medium sensitive area. We present here the multi-grid design, introduced at the ILL and developed in collaboration with ESS for LAN (large area neutron) detectors. Typically thirty (B4C)-B-10 films of 1 mu m thickness are used to convert neutrons into ionizing particles which are subsequently detected in a proportional gas counter. The principle and the fabrication of the multi-grid are described and some preliminary results obtained with a prototype of 200 cm x 8 cm are reported; a detection efficiency of 48% has been measured at 2.5 angstrom with a monochromatic neutron beam line, showing the good potential of this new technique. (C) 2013 Elsevier B.V. All rights reserved.
49.	Andersen, Lars Vabbersgaard, et al. (författare) Influence of furniture on the modal properties of wooden floors 2020 Ingår i: Model Validation and Uncertainty Quantification, Volume 3 - Proceedings of the 37th IMAC, A Conference and Exposition on Structural Dynamics 2019. - Cham : Springer International Publishing. - 9783030120740 ; , s. 197-204 Konferensbidrag (refereegranskat)abstract Structure-borne vibration and low-frequency re-radiated noise from internal and external sources cause annoyance for inhabitants in dwellings. A key parameter in the prediction of vibration and noise levels is the modal parameters of the floors in a building, since vibration and sound levels increase when natural frequencies of the floor coincide with the excitation frequencies of a source, e.g. monoharmonic vibration of unbalanced rotating machinery and appliances or HVAC system—or traffic induced ground vibration propagating into the building. This paper has focus on wooden floors built as an assembly of particleboard and timber joists. Such floors constitute horizontal divisions in many dwellings—both older, traditional buildings and new lightweight buildings. The analysis concerns the impact of furniture placed on a floor with otherwise known properties. Given the small mass of a traditional wooden floor, the presence of furniture can be expected to change the modal properties of the floor significantly. The finite-element model, developed for the present analyses, accounts for uncertainty in the position of the furniture, and the analysis addresses the importance of the elevation of the mass above the floor regarding the natural frequencies and the related modes of vibration.
50.	Andersen, N Christian (författare) On characterisation and diagnosis of frontotemporal lobar degeneration syndromes : with special reference to the progressive aphasias 2002 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Alzheimer's disease (AD) is the most common dementing brain disease, with episodic memory impairment as a characteristic early feature. However, not all primary degenerative brain syndromes include prominent deficits in day-to-day memorizing. Frontotemporal lobar degeneration (FTLD) syndromes are non-AD disorders affecting mainly the frontal and temporal cortical regions of the brain. Three major neurobehavioural syndromes can result from FTLD: a profound alteration in personality resulting in a frontotemporal dementia (FTD) and two other clinical syndromes in which impairment of language is the presenting symptom, semantic dementia (SD) and nonfluent progressive aphasia (PA). In 1892 the Austrian Arnold Pick presented the first case of progressive aphasia due to atrophy localized to the left temporal lobe, followed by Further cases in the early 20th century. The general purpose of this thesis was to call the attention of clinicians to the FTLD patients, and their specific impairments, which are now likely to be inappropriately diagnosed as having AD. The focus of this work was the progressive aphasias and the aim was to study which assessments that could be of value in identifying these conditions. In study I we characterised patients with marked left temporal lobe atrophy, assessed by magnetic resonance imaging (MRI) referred to as "temporal lobe atrophy" patients TLA. The measurements confirmed that the TLA patients had significantly smaller left temporal lobes as compared to AD and FTD, whereas the volumes of the right temporal lobes did not differ between groups. Cerebral blood flow measured by Single Photon Emission Computed Tomography (SPECT) was significantly reduced in the left temporal region. Tests of visuospatial function clearly separated the TLA group from patients with AD. Four of the six TLA patients were followed longitudinally showing the mean annual bilateral decrease of temporal lobe volumes to be 9% for the left side and 8% for the right. The possibility to use new biological and genetical markers resulted in study II and III. CSF amyloid beta protein (A-beta40) concentrations were found to be in linear relation (p<0.02) with the severity of frontal lobe atrophy in FTD. Detection of APOE allele frequencies in SD patients showed 31% for the epsilon-4 allele and 69% for epsilon-3. This overrepresentation of allele epsilon-4 was similar to what had been found in AD. Tau protein CSF concentrations in SD were found to be moderately elevated compared to healthy controls. No significant relation between tau protein CSF concentration and APOE genotype could be found, nor could any connection to disease duration be detected. In study IV 32 patients referred for primary speech-language impairments were studied retrospectively. Twenty-one cases were classified as fluent progressive aphasia. At clinical presentation, most fluent aphasics had semantic anomia and word comprehension impairment. Wherever assessed for it, associative agnosia was also present save for one patient. These patients thus fulfilled criteria for SD. The rest displayed variants of nonfluent progressive aphasia. In study V patients with SD and PA were characterised clinically. Typical age of onset of symptoms in progressive aphasia seems to be around 60 years of age regardless of aphasia type, The time span from debut to referral is 2-3 years. Both patients group showed atrophy and a reduction of cerebral blood flow in the temporal regions. The pathology was lateralised, commonly to the left side. However, the pathology in SD was focused to the temporal region while in PA the left hemisphere was affected more in general. On EEG the basal activity is typically unaffected. All except one, out of 34, patients were able to perform the figure-copying task in the Mini-Mental State Examination (MMSE), regardless of the great variety in total MMSE score. Furthermore even patients with as low MMSE score as 10 were relatively well functioning in daily life mirrored by low scores on the Global Deterioration Scale (GDS), typically GDS 2 or 3. Post-mortem examination ofone SD patient showed marked left temporal lobe atrophy (except the posterior half of the superior temporal gyros) with ubiquitin-positive neurites and intraneuronal inclusions but no signs of AD or vascular pathology. The conclusion is that SD and PA are distinct neurodegenerative disorders. It is possible to diagnose and differentiate them from AD by using standard dementia investigation assessments. Progressive aphasia with relatively preserved visuospatial functions should lead to further investigations where detection of regional cerebral blood flow with SPECT appears to be of particular value. A use of "Pick's disease" or Pick complex for FTLD and related disorders would be historically justified and would perhaps be attractive for both caregivers and patients by making the disease more comprehensive clinically, in analogy with Alzheimer's disease.

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