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Sökning: WFRF:(Martijn H)

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1.
  • Breugom, A. J., et al. (författare)
  • Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision : a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial
  • 2015
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:4, s. 696-701
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo) radiotherapy and total mesorectal excision (TME). Patients and methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1: 1) to observation or adjuvant chemotherapy after preoperative (chemo) radiotherapy and TME. Radiotherapy consisted of 5 x 5 Gy. Chemoradiotherapy consisted of 25 x 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo) radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.
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2.
  • Rutten, Martijn G. S., et al. (författare)
  • Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia
  • 2023
  • Ingår i: Cancer & Metabolism. - : Springer Nature. - 2049-3002. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGlycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia.MethodsHepatocyte-specific G6pc knockout (L-G6pc−/−) mice were treated with AAV-shChREBP to normalize hepatic ChREBP activity.ResultsHepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged.ConclusionsIn conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease.
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3.
  • Dik, Vincent K., et al. (författare)
  • Coffee and tea consumption, genotype- based CYP1A2 and NAT2 activity and colorectal cancer risk- Results from the EPIC cohort study
  • 2014
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:2, s. 401-412
  • Tidskriftsartikel (refereegranskat)abstract
    • Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.78.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.
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4.
  • Hop, Paul J., et al. (författare)
  • Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
  • 2022
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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5.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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6.
  • Alessandro, B., et al. (författare)
  • Vector boson scattering : Recent experimental and theory developments
  • 2018
  • Ingår i: Reviews in Physics. - : Elsevier BV. - 2405-4283. ; 3, s. 44-63
  • Tidskriftsartikel (refereegranskat)abstract
    • This document summarises the talks and discussions happened during the VBSCan Split17 workshop, the first general meeting of the VBSCan COST Action network. This collaboration is aiming at a consistent and coordinated study of vector-boson scattering from the phenomenological and experimental point of view, for the best exploitation of the data that will be delivered by existing and future particle colliders. 
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7.
  • Ma, Li-Jun, et al. (författare)
  • Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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9.
  • Goey, Kaitlyn K. H., et al. (författare)
  • Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer : Supported by the ARCAD Group
  • 2018
  • Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 100, s. 35-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patient characteristics and stratification factors are key features influencing trial outcomes. However, there is substantial heterogeneity in reporting of patient characteristics and use of stratification factors in phase 3 trials investigating systemic treatment of metastatic colorectal cancer (mCRC). We aimed to develop a minimum set of essential baseline characteristics and stratification factors to include in such trials. Methods: We performed a modified, two-round Delphi survey among international experts with wide experience in the conduct and methodology of phase 3 trials of systemic treatment of mCRC. Results: Thirty mCRC experts from 15 different countries completed both consensus rounds. A total of 14 patient characteristics were included in the recommended set: age, performance status, primary tumour location, primary tumour resection, prior chemotherapy, number of metastatic sites, liver-only disease, liver involvement, surgical resection of metastases, synchronous versus metachronous metastases, (K)RAS and BRAF mutation status, microsatellite instability/mismatch repair status and number of prior treatment lines. A total of five patient characteristics were considered the most relevant stratification factors: RAS/BRAF mutation status, performance status, primary tumour sidedness and liver-only disease. Conclusions: This survey provides a minimum set of essential baseline patient characteristics and stratification factors to include in phase 3 trials of systemic treatment of mCRC. Inclusion of these patient characteristics and strata in study protocols and final study reports will improve interpretation of trial results and facilitate cross-study comparisons.
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10.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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11.
  • van Schaik, Fiona D. M., et al. (författare)
  • Serological markers predict inflammatory bowel disease years before the diagnosis
  • 2013
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 62:5, s. 683-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD. Design Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy. Results A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased. Conclusion A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.
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12.
  • Andersson, J. Y., et al. (författare)
  • Quantum structure based infrared detector research and development within Acreo's centre of excellence IMAGIC
  • 2010
  • Ingår i: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 53:4, s. 227-230
  • Tidskriftsartikel (refereegranskat)abstract
    • Acreo has a long tradition of working with quantum structure based infrared (IR) detectors and arrays. This includes QWIP (quantum well infrared photodetector), QDIP (quantum dot infrared photodetector), and InAs/GaInSb based photon detectors of different structure and composition. It also covers R&D on uncooled microbolometers. The integrated thermistor material of such detectors is advantageously based on quantum structures that are optimised for high temperature coefficient and low noise. Especially the SiGe material system is preferred due to the compatibility with silicon technology. The R&D work on IR detectors is a prominent part of Acreo's centre of excellence "IMAGIC" on imaging detectors and systems for non-visible wavelengths. IMAGIC is a collaboration between Acreo, several industry partners and universities like the Royal Institute of Technology (KTH) and Linkoping University. (C) 2010 Elsevier B.V. All rights reserved.
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14.
  • Becher, Tobias H., et al. (författare)
  • Prolonged Continuous Monitoring of Regional Lung Function in Infants with Respiratory Failure
  • 2022
  • Ingår i: Annals of the American Thoracic Society. - : American Thoracic Society. - 2329-6933 .- 2325-6621. ; 19:6, s. 991-999
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Electrical impedance tomography (EIT) allows instantaneous and continuous visualization of regional ventilation and changes in end-expiratory lung volume at the bedside. There is particular interest in using EIT for monitoring in critically ill neonates and young children with respiratory failure. Previous studies have focused only on short-term monitoring in small populations. The feasibility and safety of prolonged monitoring with EIT in neonates and young children have not been demonstrated yet.Objectives: To evaluate the feasibility and safety of long-term EIT monitoring in a routine clinical setting and to describe changes in ventilation distribution and homogeneity over time and with positioning in a multicenter cohort of neonates and young children with respiratory failure.Methods: At four European University hospitals, we conducted an observational study (NCT02962505) on 200 patients with postmenstrual ages (PMA) between 25 weeks and 36 months, at risk for or suffering from respiratory failure. Continuous EIT data were obtained using a novel textile 32-electrode interface and recorded at 48 images/s for up to 72 hours. Clinicians were blinded to EIT images during the recording. EIT parameters and the effects of body position on ventilation distribution were analyzed offline. Results: The average duration of FAT measurements was 53 +/- 20 hours. Skin contact impedance was sufficient to allow image reconstruction for valid ventilation analysis during a median of 92% (interquartile range, 77-98%) of examination time. EIT examinations were well tolerated, with minor skin irritations (temporary redness or imprint) occurring in 10% of patients and no moderate or severe adverse events. Higher ventilation amplitude was found in the dorsal and right lung areas when compared with the ventral and left regions, respectively. Prone positioning resulted in an increase in the ventilation-related EIT signal in the dorsal hemithorax, indicating increased ventilation of the dorsal lung areas. Lateral positioning led to a redistribution of ventilation toward the dependent lung in preterm infants and to the nondependent lung in patients with PMA > 37 weeks.Conclusions: EIT allows continuous long-term monitoring of regional lung function in neonates and young children for up to 72 hours with minimal adverse effects. Our study confirmed the presence of posture-dependent changes in ventilation distribution and their dependency on PMA in a large patient cohort.
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15.
  • Bonjer, H Jaap, et al. (författare)
  • A randomized trial of laparoscopic versus open surgery for rectal cancer.
  • 2015
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 372:14, s. 1324-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer.
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16.
  • Cox, M., et al. (författare)
  • Spectroscopic evidence for trap-dominated magnetic field effects in organic semiconductors
  • 2014
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 90:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Polaron traps are ubiquitous in organic semiconductors and recent evidence suggests they might be crucial for the large observed magnetic field effects (MFEs) in organic semiconductors. Here we measure MFEs in polymer thin-film devices with engineered, radiative trap sites in order to spectroscopically investigate the influence of the traps. Surprisingly, the luminescence at the trap sites and the polymer backbone is found to have an opposite response to a magnetic field. All our results are compatible with a mechanism in which spin mixing at the traps can create the large MFEs observed on the backbone. This scenario is quantitatively confirmed by numerical drift-diffusion modeling with magnetic-field-dependent exciton densities at the traps. These insights solve an outstanding controversy within the research field.
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17.
  • Degen, Winfried G. J., et al. (författare)
  • Characterization of recombinant human autoantibody fragments directed toward the autoantigenic U1-70K protein
  • 2000
  • Ingår i: European Journal of Immunology. - : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 30:10, s. 3029-3038
  • Tidskriftsartikel (refereegranskat)abstract
    • The U1-70K protein is specifically bound to stemloop I of the U1 small nuclear RNA contained in the U1 small nuclear ribonucleoprotein complex (U1 snRNP), which is involved in the splicing of pre-mRNA. All components of the U1 snRNP complex, including the U1-70K protein, are important autoantigens in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Here we describe for the first time the selection and characterization of recombinant human anti-U1-70K single chain autoantibody fragments (anti-hU1-70K scFv) from autoimmune patient-derived phage display antibody libraries. All scFv specifically recognize parts of the hU1-70K protein and its apoptotic 40-kDa cleavage product. In Western blotting assays a number of scFv preferentially recognize the 40-kDa apoptotic cleavage fragment of the U1-70K protein, suggesting a possible involvement of this apoptotic cleavage product in the autoimmune response of patients. The germline gene usage of these recombinant autoantibodies was also determined. Using several U1-70K deletion and point mutants of both human (h) and Drosophila melanogaster (Dm) origin, it was established that the U1-70K epitope that is recognized by the anti-hU1-70K scFv is located within the RNA binding domain.
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18.
  • Escaned, Javier, et al. (författare)
  • Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes
  • 2018
  • Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 11:15, s. 1437-1449
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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19.
  • Goey, Kaitlyn K. H., et al. (författare)
  • Reporting of patient characteristics and stratification factors in phase 3 trials investigating first-line systemic treatment of metastatic colorectal cancer : A systematic review
  • 2018
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 96, s. 115-124
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Patient characteristics and stratification factors are important factors influencing trial outcomes. Uniform reporting on these parameters would facilitate cross-study comparisons and extrapolation of trial results to clinical practice. In 2007, standardisation on patient characteristics reporting and stratification in metastatic colorectal cancer (mCRC) trials was proposed. We investigated the reporting of prognostic factors and implementation of this proposal in mCRC trials published from 2005 to 2016.Methods: We searched PubMed and Embase (January 2005 – June 2016) for first-line phase 3 mCRC trials. Patient characteristics reporting and use of stratification factors were extracted and analysed for adherence to the proposal from 2007.Results: Sixty-seven trials (35,315 patients) were identified, reporting 48 different patient characteristics (median: 9 [range: 5–18] per study). Age, gender, performance status (PS), primary tumour site and adjuvant chemotherapy were frequently reported (87%–100%), in contrast to laboratory values, such as alkaline phosphatase, lactate dehydrogenase and white blood cell count (10%–25%). We identified 29 different stratification factors (median: 3 [range: 1–9] per study). The most common strata were PS and treatment centre (>60%). A median of 8/12 (range: 4–11) of the proposed parameters was reported. Although the percentage of studies reporting each factor slightly increased over time, there was no significant correlation between publication year and adherence to the proposal from 2007.Conclusions: We observed persistent heterogeneity in the reporting of patient characteristics and use of stratification factors in first-line mCRC trials. The proposal from 2007 has not led to increased uniformity of patient characteristics reporting and use of stratification over time. There is an urgent need to address this issue to improve the interpretation of trial results.
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20.
  • Gustafsson, Oscar, et al. (författare)
  • Long-wavelength infrared quantum-dot based interband photodetectors
  • 2011
  • Ingår i: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 54:3, s. 287-291
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the design and fabrication of (Al)GaAs(Sb)/InAs tensile strained quantum-dot (QD) based detector material for thermal infrared imaging applications in the long-wavelength infrared (LWIR) regime. The detection is based on transitions between confined dot states and continuum states in a type-II band lineup, and we therefore refer to it as a dot-to-bulk (D2B) infrared photodetector with expected benefits including long carrier lifetime due to the type-II band alignment, suppressed Shockley-Read-Hall generation-recombination due to the relatively large-bandgap matrix material, inhibited Auger recombination processes due to the tensile strain and epitaxial simplicity. Metal-organic vapor-phase epitaxy was used to grow multiple (Al)GaAs(Sb) QD layers on InAs substrates at different QD nominal thicknesses, compositions, doping conditions and multilayer periods, and the material was characterized using atomic force and transmission electron microscopy, and Fourier-transform infrared absorption spectroscopy. Dot densities up to 1 x 10(11) cm(-2), 1 x 10(12) cm(-2) and 3 x 10(10) cm(-2) were measured for GaAs, AlGaAs and GaAsSb QDs, respectively. Strong absorption in GaAs, AlGaAs and GaAsSb multilayer QD samples was observed in the wavelength range 6-12 mu m. From the wavelength shift in the spectral absorption for samples with varying QD thickness and composition it is believed that the absorption is due to an intra- valance band transition. From this it is possible to estimate the type-II inter-band transition wavelength, thereby suggesting that (Al)GaAs(Sb) QD/InAs heterostructures are suitable candidates for LWIR detection and imaging.
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22.
  • Horikoshi, Momoko, et al. (författare)
  • Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
  • 2015
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
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23.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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24.
  • Kemerink, Martijn, et al. (författare)
  • Optical detection of ballistically injected electrons in III/V heterostructures
  • 2001
  • Ingår i: Applied Physics A. - : Springer Verlag (Germany). - 0947-8396 .- 1432-0630. ; 72, s. S201-S204
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a novel spectroscopic technique that is based on the ballistic injection of minority carriers from the tip of a scanning-tunneling microscope into a semiconductor heterostructure. By analyzing the resulting electro-luminescence spectrum as a function of tip-sample bias, both the injection barrier height and the carrier relaxation rate Gamma(s) after injection can be determined. At 4.2 K we found Gamma(s) = 5 x 10(13) s(-1) and at 77 K we found Gamma(s) = 8 x 10(13) s(-1). From current-dependent measurements we find that, at room temperature, a large fraction of the carriers is trapped prior to radiative recombination. At high currents or low temperatures the traps become saturated. We tentatively identify the Be acceptors in the structure as trapping centers.
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25.
  • Kemerink, Martijn, et al. (författare)
  • Optical properties of a tip-induced quantum dot
  • 2001
  • Ingår i: Applied Physics A. - : Springer Verlag (Germany). - 0947-8396 .- 1432-0630. ; 72, s. S239-S242
  • Tidskriftsartikel (refereegranskat)abstract
    • We have performed optical spectroscopy measurements on a STM-tip-induced quantum dot in a GaAs layer. The dominant confinement in the (hole) quantum dot is found to be in the direction parallel to the tip axis. Electron confinement is achieved by a sub-surface AlGaAs barrier. Current-dependent measurements indicate that many-body interactions can cause spectral blueshifts up to 75 meV for a tunneling current of 10 nA. Consequently, a full treatment of the many-body problem is required for an accurate description of this type of system.
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26.
  • Koivula, Robert, et al. (författare)
  • Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : rationale and design of the epidemiological studies within the IMI DIRECT Consortium
  • 2014
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:6, s. 1132-1142
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS:The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.METHODS:Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires.CONCLUSIONS/INTERPRETATION:DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes
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27.
  • Lahrouchi, Najim, et al. (författare)
  • Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
  • 2020
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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28.
  • Luecken, Malte D., et al. (författare)
  • The discovAIR project : a roadmap towards the Human Lung Cell Atlas
  • 2022
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60:2
  • Forskningsöversikt (refereegranskat)abstract
    • The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The Lung Biological Network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and cell-cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework programme. discovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Human Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Human Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions.
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29.
  • Maier, Hannes, et al. (författare)
  • Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
  • 2022
  • Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
  •  
30.
  • Martijn, H., et al. (författare)
  • Development of IR imaging at IRnova
  • 2009
  • Ingår i: Infrared Technology and Applications XXXV. - : SPIE.
  • Konferensbidrag (refereegranskat)abstract
    • Historically IRnova has exclusively been a company, focused on manufacturing of QWIP detectors. Nowadays, besides continuous improvements of the performance of QWIP FPAs and development of new formats IRnova is involved in development of QWIP detectors for special applications and has started the development of the next generation infrared detectors, as well. In the light of the development of new formats we validate experimentally theoretical calculations of the response of QWIPs for smaller pixel size. These results allow for the development of high performance megapixel QWIP FPA that exhibit the high uniformity and operability QWIP detectors are known for. QWIP is also being considered for space applications. The requirements on dark current and operating temperature are however much more stringent as compared to the terrestrial applications. We show ways to improve the material quality with as a result a higher detector operating temperature. IRnova is also looking at antimony-based strained superlattice material for the LWIR region together with partners at theIMAGIC centre of excellence. One of the ways to overcome the problem with surface currents is passivating overgrowth. We will report the status and results of overgrowing the detector mesas with AlGa(As)Sb in a MOVPE system. At the same centre of excellence a novel material concept is being developed for LWIR detection. This new material contains a superlattice of vertically aligned and electronically coupled InAs and GaSb quantum dots. Simulations show that it should be possible to have LWIR detection in this material. We will present the current status and report results in this research.
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31.
  • Maturova, Klara, et al. (författare)
  • Scanning Kelvin Probe Microscopy on Bulk Heterojunction Polymer Blends
  • 2009
  • Ingår i: Advanced Functional Materials. - : Wiley-VCH Verlag. - 1616-301X .- 1616-3028. ; 19:9, s. 1379-1386
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, correlated AFM and scanning Kelvin probe microscopy measurements with sub-100 nm resolution on the phase-separated active layer of polymer-fullerene (MDMO-PPV:PCBM) bulk heterojunction solar cells in the dark and under illumination are described. Using numerical modeling a fully quantitative explanation for the contrast and shifts of the surface potential in dark and light is provided. Under illumination an excess of photogenerated electrons is present in both the donor and acceptor phases. From the time evolution of the surface potential after switching off the light the contributions of free and trapped electrons can be identified. Based on these measurements the relative 3D energy level shifts of the sample are calculated. Moreover, by comparing devices with fine and coarse phase separation, it is found that the inferior performance of the latter devices is, at least partially, due to poor electron transport.
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32.
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33.
  • Santangelo, James S., et al. (författare)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Tidskriftsartikel (refereegranskat)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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34.
  • Schouten, Stefan, et al. (författare)
  • An interlaboratory study of TEX86 and BIT analysis of sediments, extracts, and standard mixtures
  • 2013
  • Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 14:12, s. 5263-5285
  • Tidskriftsartikel (refereegranskat)abstract
    • Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility +/- 3-4 degrees C when translated to temperature) but a large spread in BIT measurements (reproducibility +/- 0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0 degrees C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the true (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values.
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35.
  • Srivastava, Ankur, 1989, et al. (författare)
  • A DSO Support Framework for Assessment of Future-Readiness of Distribution Systems: Technical, Market, and Policy Perspectives
  • 2019
  • Ingår i: CIRED Conference Proceedings. - 2032-9644. - 9782960241501
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the initial ideas for a framework to support the distribution system operators for assessing current status of network infrastructures, market/business models, and policies applicable to distribution systems, and thus identify future-readiness of their network. The assessment framework consists of two steps as the identification of the key indicators associated with this transition and assessing the current status by evaluation of these indicators based on inputs from distribution system operators. Case studies have been carried out for distribution system operators in three European countries, i.e., Göteborg Energi (Sweden), SOREA (France), and ENEXIS (The Netherlands). The key results have shown that presently the three distribution system operators have a small proportion of renewable power generation in their grids, but it is going to increase in the future. Hence, they need investments in flexibilities, generation and load forecasting, advanced network control, and protection strategies, etc. The results also suggest needs for development of novel business models for customers and changes in the policy and regulations. Finally, a comparative assessment of three distribution system operators is presented in the paper.
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36.
  • ter Veer, Emil, et al. (författare)
  • Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease
  • 2018
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 19:3, s. E151-E160
  • Forskningsöversikt (refereegranskat)abstract
    • Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.
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37.
  • Verheus, Martijn, et al. (författare)
  • Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density
  • 2008
  • Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 112:1, s. 109-122
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. OBJECTIVES: We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. DESIGN AND METHODS: Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. RESULTS: The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and higher. CONCLUSION: Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.
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38.
  • Voss, Erica A, et al. (författare)
  • Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.
  • 2023
  • Ingår i: EClinicalMedicine. - 2589-5370. ; 58
  • Tidskriftsartikel (refereegranskat)abstract
    • Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.None.
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39.
  • Waeijen-Smit, Kiki, et al. (författare)
  • Global mortality and readmission rates following COPD exacerbation-related hospitalisation : a meta-analysis of 65 945 individual patients
  • 2024
  • Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations < 12 months prior to the index event. Conclusions This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.
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40.
  • Western, Benedikte, et al. (författare)
  • Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study
  • 2024
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Chichester, West Sussex : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 34:2, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects. © 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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41.
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42.
  • Amato, Fulvio, et al. (författare)
  • Urban air quality : The challenge of traffic non-exhaust emissions
  • 2014
  • Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 275, s. 31-36
  • Tidskriftsartikel (refereegranskat)abstract
    • About 400,000 premature adult deaths attributable to air pollution occur each year in the European Region. Road transport emissions account for a significant share of this burden. While important technological improvements have been made for reducing particulate matter (PM) emissions from motor exhausts, no actions are currently in place to reduce the non-exhaust part of emissions such as those from brake wear, road wear, tyre wear and road dust resuspension. These "non-exhaust" sources contribute easily as much and often more than the tailpipe exhaust to the ambient air PM concentrations in cities, and their relative contribution to ambient PM is destined to increase in the future, posing obvious research and policy challenges.This review highlights the major and more recent research findings in four complementary fields of research and seeks to identify the current gaps in research and policy with regard to non-exhaust emissions. The objective of this article is to encourage and direct future research towards an improved understanding on the relationship between emissions, concentrations, exposure and health impact and on the effectiveness of potential remediation measures in the urban environment.
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43.
  • Apps, Richard, et al. (författare)
  • Cerebellar Modules and Their Role as Operational Cerebellar Processing Units
  • 2018
  • Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 17:5, s. 654-682
  • Tidskriftsartikel (refereegranskat)abstract
    • The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form.
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44.
  • Arheimer, Berit, et al. (författare)
  • The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
  • 2024
  • Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
  • Tidskriftsartikel (refereegranskat)abstract
    • The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
  •  
45.
  • Beverborg, Niels Grote, et al. (författare)
  • Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy
  • 2021
  • Ingår i: Nature Communications. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 2041-1723.
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp−/−), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF.
  •  
46.
  • Birkhofer, Klaus, et al. (författare)
  • Long-term organic farming fosters below and aboveground biota: Implications for soil quality, biological control and productivity
  • 2008
  • Ingår i: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 40:9, s. 2297-2308
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic farming may contribute substantially to future agricultural production worldwide by improving soil quality and pest control, thereby reducing environmental impacts of conventional farming. We investigated in a comprehensive way soil chemical, as well as below and aboveground biological parameters of two organic and two conventional wheat farming systems that primarily differed in fertilization and weed management strategies. Contrast analyses identified management related differences between "herbicide-free" bioorganic (BIOORG) and biodynamic (BIODYN) systems and conventional systems with (CONFYM) or without manure (CONMIN) and herbicide application within a long-term agricultural experiment (DOK trial, Switzerland). Soil carbon content was significantly higher in systems receiving farmyard manure and concomitantly microbial biomass (fungi and bacteria) was increased. Microbial activity parameters, such as microbial basal respiration and nitrogen mineralization, showed an opposite pattern, suggesting that soil carbon in the conventional system (CONFYM) was more easily accessible to microorganisms than in organic systems. Bacterivorous nematodes and earthworms were most abundant in systems that received farmyard manure, which is in line with the responses of their potential food sources (microbes and organic matter). Mineral fertilizer application detrimentally affected enchytraeids and Diptera larvae, whereas aphids benefited. Spider abundance was favoured by organic management, most likely a response to increased prey availability from the belowground subsystem or increased weed coverage. In contrast to most soil-based, bottom-up controlled interactions, the twofold higher abundance of this generalist predator group in organic systems likely contributed to the significantly lower abundance of aboveground herbivore pests (aphids) in these systems. Long-term organic farming and the application of farmyard manure promoted soil quality, microbial biomass and fostered natural enemies and ecosystem engineers, suggesting enhanced nutrient cycling and pest control. Mineral fertilizers and herbicide application, in contrast, affected the potential for top-down control of aboveground pests negatively and reduced the organic carbon levels. Our study indicates that the use of synthetic fertilizers and herbicide application changes interactions within and between below and aboveground components, ultimately promoting negative environmental impacts of agriculture by reducing internal biological cycles and pest control. On the contrary, organic farming fosters microbial and faunal decomposers and this propagates into the aboveground system via generalist predators thereby increasing conservation biological control. However, grain and straw yields were 23% higher in systems receiving mineral fertilizers and herbicides reflecting the trade-off between productivity and environmental responsibility. (C) 2008 Elsevier Ltd. All rights reserved.
  •  
47.
  • Bobbert, PA, et al. (författare)
  • Exchange-correlation energy of a hole gas including valence band coupling
  • 1997
  • Ingår i: Physical Review B Condensed Matter. - : American Physical Society. - 0163-1829 .- 1095-3795. ; 56:7, s. 3664-3671
  • Tidskriftsartikel (refereegranskat)abstract
    • We have calculated an accurate exchange-correlation energy of a hole gas, including the complexities related to the valence band coupling as occurring in semiconductors like GaAs, but excluding the band warping. A parametrization for the dependence on the density and the ratio between light-and heavy-hole masses is given. We apply our results to a hole gas in an AlxGa1-xAs/GaAs/AlxGa1-xAs quantum well and calculate the two-dimensional band structure and the band-gap renormalization. The inclusion of the valence band coupling in the calculation of the exchange-correlation potentials for holes and electrons leads to a much better agreement between theoretical and experimental data than when it is omitted.
  •  
48.
  • 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.
  •  
49.
  • Charrier, Dimitri S. H., et al. (författare)
  • Large Electrically Induced Height and Volume Changes in Poly(3,4-ethylenedioxythiophene)/Poly(styrenesulfonate) Thin Films
  • 2010
  • Ingår i: Chemistry of Materials. - : American Chemical Society. - 0897-4756 .- 1520-5002. ; 22:12, s. 3670-3677
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate large, partly reversible height and volume changes of thin films of poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) on the anode of interdigitating gold electrodes under ambient conditions by applying an electrical bias. The height and volume changes were monitored with optical and atomic force microscopy and are found to be independent of initial film thickness. In the first cycle, a relative height change of 950% is observed for a 21 nm thick film. Two regimes are identified. In the first regime, reversible redox reactions occur and reversible height changes can be ascribed to absorption of water via osmotic effects, brought about by an increasing ion concentration on the anode. In the second, irreversible regime, irreversible overoxidation of the PEDOT occurs and mass transport from the channel to the anode becomes important.
  •  
50.
  • Charrier, Dimitri S. H., et al. (författare)
  • Real versus measured surface potentials in scanning Kelvin probe microscopy
  • 2008
  • Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 2:4, s. 622-626
  • Tidskriftsartikel (refereegranskat)abstract
    • Noncontact potentiometry or scanning Kelvin probe microscopy (SKPM) is a widely used technique to study charge injection and transport in (in)organic devices by measuring a laterally resolved local potential. This technique suffers from the significant drawback that experimentally obtained curves do not generally reflect the true potential profile in the device due to nonlocal coupling between the probing tip and the device. In this work, we quantitatively explain the experimental SKPM response and by doing so directly link theoretical device models to real observables. In particular, the model quantitatively explains the effects of the tip-sample distance and the dependence on the orientation of the probing tip with respect to the device.
  •  
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