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3.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Andreoni, I., et al. (författare)
  • Follow Up of GW170817 and Its Electromagnetic Counterpart by Australian-Led Observing Programmes
  • 2017
  • Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
  • Forskningsöversikt (refereegranskat)abstract
    • The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (similar to 2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
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  • 2019
  • Tidskriftsartikel (refereegranskat)
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7.
  • Dujon, B, et al. (författare)
  • The nucleotide sequence of Saccharomyces cerevisiae chromosome XV
  • 1997
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 387:6632, s. 98-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.
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8.
  • Hancock, Dana B, et al. (författare)
  • Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
  • 2012
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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9.
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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10.
  • Forslund, Sofia K., et al. (författare)
  • Combinatorial, additive and dose-dependent drug–microbiome associations
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
  • Tidskriftsartikel (refereegranskat)abstract
    • During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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  • Imanishi, T., et al. (författare)
  • Integrative annotation of 21,037 human genes validated by full-length cDNA clones
  • 2004
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
  • Tidskriftsartikel (refereegranskat)abstract
    • The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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12.
  • Molinaro, Antonio, et al. (författare)
  • Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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  • Köttgen, Anna, et al. (författare)
  • New loci associated with kidney function and chronic kidney disease
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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  • Anderson, Cynthia M., et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
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16.
  • Andrikopoulos, Petros, et al. (författare)
  • Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
  • 2023
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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17.
  • Bertola, Laura D., et al. (författare)
  • A pragmatic approach for integrating molecular tools into biodiversity conservation
  • 2024
  • Ingår i: Conservation science and practice. - 2578-4854. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation. Molecular tools are increasingly applied in conservation management; however, they are not equally available to all practitioners. We here provide key questions when establishing a conservation genetic study and highlight important steps which need to be addressed when these tools are globally applied.image
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18.
  • Cassagne, Thierry B., et al. (författare)
  • Long term corrosion testing and monitoring of oxygen and corrosion potential in an umbilical design
  • 2012
  • Ingår i: NACE - International Corrosion Conference Series. - 9781622760787 ; , s. 1096-1108
  • Konferensbidrag (refereegranskat)abstract
    • Subsea umbilicals are used for control and operation of subsea oil and gas production facilities. Typically an umbilical consists of steel tubes, electrical cables, fiber optic cables, weight or strength elements and fillers. Super duplex stainless steel tube material has been used for almost 20 years within the umbilical industry. However, a recent failure on two orbital welds of 25Cr super duplex of an umbilical installed in the South China Sea was reported. From these results some umbilical end users recommended the use of thermoplastic coating to avoid crevice corrosion on 25Cr super duplex stainless steel above 20°C. However, this limit is based on results obtained for super duplex stainless steel in aerated natural seawater and very little is known on the micro-environment formed by the confined seawater between metallic tubes and polymer matrix of an umbilical. This work reports corrosion potential and oxygen content measurements in the confined zone between the metallic tubes and the polymer matrix of an umbilical. These measurements were performed using micro-electrodes on a 2 meter long real umbilical at 30°C in heated natural seawater. From the measurements, it is shown that the oxygen content in the confined zone is rapidly consumed probably due to the passive current on the stainless steel tubes and then remains below 2 ppm over one year exposure period. From the open-circuit potential measurements performed in the confined zone, it is clear that the open circuit potential remained below -150 mV/AgCl. This translates an absence of electrochemical effect of the biofilm in the confined zone. Visual and metallographic examinations of the tubes after exposure confirmed the results obtained by the microelectrodes and clearly indicate that no corrosion initiation occurred on superduplex stainless steel (base metal and welds) under these experimental conditions. The results are discussed in view of the validity of corrosion tests performed under aerated conditions and the need of further developments of new testing procedures to represent the confined situation in the umbilical design.
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20.
  • Coomans, Marijke B., et al. (författare)
  • Measuring change in health-related quality of life: the impact of different analytical methods on the interpretation of treatment effects in glioma patients
  • 2020
  • Ingår i: Neuro-Oncology Practice. - : OXFORD UNIV PRESS. - 2054-2577 .- 2054-2585. ; 7:6, s. 668-675
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions. Methods. HRQoL data from 15 randomized clinical trials were combined (CODAGLIO project). Change in HRQoL scores, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN20 questionnaires, was analyzed in 3 ways: (1) at the group level, comparing mean changes in scale/item scores between treatment arms, (2) at the patient level per scale/item, calculating the percentage of patients that deteriorated, improved, or remained stable per scale/item, and (3) at the individual patient level, combining all scales/items. Results. Baseline and first follow-up HRQoL data were available for 3727 patients. At the group scale/item level, only the item "hair loss" showed a significant and clinically relevant change (ie, >= 10 points) over time, whereas change scores on the other scales/items were statistically significant only (all P <.001; range in change score, 0.1-6.2). Although a large proportion of patients had stable HRQoL over time (range, 27%-84%) on the patient level per scale/item, many patients deteriorated (range, 6%-43%) or improved (range, 8%-32%) on a specific scale/item. At the individual patient level, the majority of patients (86%) showed both deterioration and improvement, whereas only 1% remained stable on all scales. Conclusions. Different analytical methods of changes in HRQoL result in distinct conclusions of treatment effects, all of which may be relevant for informing clinical decision making.
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21.
  • Coomans, Marijke B., et al. (författare)
  • Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?
  • 2019
  • Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 21:11, s. 1447-1457
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (amp;gt;= 10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P amp;lt; 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P amp;lt; 0.001), independent of other factors. Conclusions. Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients functioning as measured with a self-report questionnaire.
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22.
  • Hubert, D., et al. (författare)
  • Ground-based assessment of the bias and long-term stability of 14 limb and occultation ozone profile data records
  • 2016
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:6, s. 2497-2534
  • Tidskriftsartikel (refereegranskat)abstract
    • The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of 14 limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements. In particular, we considered the latest operational Level-2 records by SAGE II, SAGE III, HALOE, UARS MLS, Aura MLS, POAM II, POAM III, OSIRIS, SMR, GOMOS, MIPAS, SCIAMACHY, ACE-FTS and MAESTRO. Central to our work is a consistent and robust analysis of the comparisons against the ground-based ozonesonde and stratospheric ozone lidar networks. It allowed us to investigate, from the troposphere up to the stratopause, the following main aspects of satellite data quality: long-term stability, overall bias and short-term variability, together with their dependence on geophysical parameters and profile representation. In addition, it permitted us to quantify the overall consistency between the ozone profilers. Generally, we found that between 20 and 40km the satellite ozone measurement biases are smaller than ±5%, the short-term variabilities are less than 5-12% and the drifts are at most ±5%decade-1 (or even ±3%decade-1 for a few records). The agreement with ground-based data degrades somewhat towards the stratopause and especially towards the tropopause where natural variability and low ozone abundances impede a more precise analysis. In part of the stratosphere a few records deviate from the preceding general conclusions; we identified biases of 10% and more (POAM II and SCIAMACHY), markedly higher single-profile variability (SMR and SCIAMACHY) and significant long-term drifts (SCIAMACHY, OSIRIS, HALOE and possibly GOMOS and SMR as well). Furthermore, we reflected on the repercussions of our findings for the construction, analysis and interpretation of merged data records. Most notably, the discrepancies between several recent ozone profile trend assessments can be mostly explained by instrumental drift. This clearly demonstrates the need for systematic comprehensive multi-instrument comparison analyses.
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23.
  • Kurz, Alexander, et al. (författare)
  • RHAPSODY - Internet-based support for caregivers of people with young onset dementia : program design and methods of a pilot study
  • 2016
  • Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 28:12, s. 2091-2099
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Young Onset Dementia (YOD), defined by first symptoms of cognitive or behavioral decline occurring before the age of 65 years, is relatively rare compared to dementia of later onset, but it is associated with diagnostic difficulty and heavy burden on affected individuals and their informal carers. Existing health and social care structures rarely meet the needs of YOD patients. Internet-based interventions are a novel format of delivering health-related education, counseling, and support to this vulnerable yet underserved group. Methods: The RHAPSODY (Research to Assess Policies and Strategies for Dementia in the Young) project is a European initiative to improve care for people with YOD by providing an internet-based information and skill-building program for family carers. The e-learning program focuses on managing problem behaviors, dealing with role change, obtaining support, and looking after oneself. It will be evaluated in a pilot study in three countries using a randomized unblinded design with a wait-list control group. Participants will be informal carers of people with dementia in Alzheimer's disease or behavioral-variant Frontotemporal degeneration with an onset before the age of 65 years. The primary outcome will be caregiving self-efficacy after 6 weeks of program use. As secondary outcomes, caregivers' stress and burden, carer health-related quality of life, caring-related knowledge, patient problem behaviors, and user satisfaction will be assessed. Program utilization will be monitored and a health-economic evaluation will also be performed. Conclusions: The RHAPSODY project will add to the evidence on the potential and limitations of a conveniently accessible, user-friendly, and comprehensive internet-based intervention as an alternative for traditional forms of counseling and support in healthcare, aiming to optimize care and support for people with YOD and their informal caregivers.
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24.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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25.
  • Parma, Valentina, et al. (författare)
  • More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis
  • 2020
  • Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 45:7, s. 609-622
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
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26.
  • Valassi, E., et al. (författare)
  • High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
  • 2019
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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27.
  • Ågren, Joakim, et al. (författare)
  • In silico and in vitro evaluation of PCR-based assays for the detection of Bacillus anthracis chromosomal signature sequences
  • 2013
  • Ingår i: Virulence. - : Taylor and Francis Inc.. - 2150-5594 .- 2150-5608. ; 4:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacillus anthracis, the causative agent of anthrax, is a zoonotic pathogen that is relatively common throughout the world and may cause life threatening diseases in animals and humans. There are many PCR-based assays in use for the detection of B. anthracis. While most of the developed assays rely on unique markers present on virulence plasmids pXO1 and pXO2, relatively few assays incorporate chromosomal DNA markers due to the close relatedness of B. anthracis to the B. cereus group strains. For the detection of chromosomal DNA, different genes have been used, such as BA813, rpoB, gyrA, plcR, S-layer, and prophage-lambda. Following a review of the literature, an in silico analysis of all signature sequences reported for identification of B. anthracis was conducted. Published primer and probe sequences were compared for specificity against 134 available Bacillus spp. genomes. Although many of the chromosomal targets evaluated are claimed to be specific to B. anthracis, cross-reactions with closely related B. cereus and B. thuringiensis strains were often observed. Of the 35 investigated PCR assays, only 4 were 100% specific for the B. anthracis chromosome. An interlaboratory ring trial among five European laboratories was then performed to evaluate six assays, including the WHO recommended procedures, using a collection of 90 Bacillus strains. Three assays performed adequately, yielding no false positive or negative results. All three assays target chromosomal markers located within the lambdaBa03 prophage region (PL3, BA5345, and BA5357). Detection limit was further assessed for one of these highly specific assays. © 2013 Landes Bioscience.
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28.
  • Abi Nassif, L., et al. (författare)
  • Reduction of potential ennoblement of stainless steel in natural seawater by an ecofriendly biopolymer
  • 2020
  • Ingår i: Journal of Environmental Chemical Engineering. - : Elsevier Ltd. - 2213-3437. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of biofilm formation on passive stainless steel in seawater environments is of primary importance since it leads to potential ennoblement of surfaces and subsequently to localized corrosion such as pitting and crevice corrosion. This study aims at developing an ecofriendly alginate biopolymer containing both non-toxic calcium and a limited amount of biocidal zinc ions which inhibits this effect. For this purpose, calcium alginate containing less than 1 % of zinc ions localized in the vicinity of the steel surface in natural and renewed seawater is demonstrated to reduce significantly the ennoblement process of steel. After 1 month of immersion, a mass loss of only 4 % of the active material is observed authorizing thereby long-term protection of steel in real environment. 
  •  
29.
  • Angiuli, C., et al. (författare)
  • Syntax and models of Cartesian cubical type theory
  • 2021
  • Ingår i: Mathematical Structures in Computer Science. - : Cambridge University Press (CUP). - 0960-1295 .- 1469-8072. ; 31:4, s. 424-468
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a cubical type theory based on the Cartesian cube category (faces, degeneracies, symmetries, diagonals, but no connections or reversal) with univalent universes, each containing pi, sigma, path, identity, natural number, boolean, suspension, and glue (equivalence extension) types. The type theory includes a syntactic description of a uniform Kan operation, along with judgmental equality rules defining the Kan operation on each type. The Kan operation uses both a different set of generating trivial cofibrations and a different set of generating cofibrations than the Cohen, Coquand, Huber, and Mortberg (CCHM) model. Next, we describe a constructive model of this type theory in Cartesian cubical sets. We give a mechanized proof, using Agda as the internal language of cubical sets in the style introduced by Orton and Pitts, that glue, pi, sigma, path, identity, boolean, natural number, suspension types, and the universe itself are Kan in this model, and that the universe is univalent. An advantage of this formal approach is that our construction can also be interpreted in a range of other models, including cubical sets on the connections cube category and the De Morgan cube category, as used in the CCHM model, and bicubical sets, as used in directed type theory.
  •  
30.
  • Armstrong, Paul W., et al. (författare)
  • Efficacy and safety of unfractionated heparin versus enoxaparin : a pooled analysis of ASSENT-3 and -3 PLUS data
  • 2006
  • Ingår i: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel. - : CMA Joule Inc.. - 0820-3946 .- 1488-2329. ; 174:10, s. 1421-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. METHODS: We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. RESULTS: The efficacy end point (a composite of 30-day mortality, reinfarction or refractory ischemia) was 12.2% with enoxaparin versus 16.0% with unfractionated heparin (p < 0.001); the combined end point of efficacy plus safety (a composite of 30-day mortality, reinfarction, refractory ischemia, intracranial hemorrhage [ICH] or major systemic bleeding) was 15.0% versus 18.0%, respectively (p = 0.003) [corrected] The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. INTERPRETATION: These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.
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31.
  • Atla, Goutham, et al. (författare)
  • Genetic regulation of RNA splicing in human pancreatic islets
  • 2022
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-760X. ; 23, s. 1-28
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundNon-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.ResultsWe examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3.ConclusionsThese data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.
  •  
32.
  • Augustine, Robin, 1982-, et al. (författare)
  • Polymeric ferrite sheats for SAR reduction of Wearable ANtennas
  • 2010
  • Ingår i: Electronics Letters. - UK : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 46:3, s. 197-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduction of specific absorption rate (SAR) has now become a buzz word because of the growing health concerns over microwave exposure. Ferrites are found to be effective in diminishing electromagnetic influence. In this reported work, flexible polymeric ferrite sheets are characterised on the basis of their shielding efficiencies. SAR measurements are carried out with a planar wearable antenna and polymeric ferrite shielding to confirm its competence.
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33.
  • Barras, B., et al. (författare)
  • A generalization of the Takeuti-Gandy interpretation
  • 2015
  • Ingår i: Mathematical Structures in Computer Science. - : Cambridge University Press (CUP). - 0960-1295 .- 1469-8072. ; 25:5, s. 1071-1099
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an interpretation of a version of dependent type theory where a type is interpreted by a Kan semisimplicial set. This interprets only a weak notion of conversion similar to the one used in the first published version of Martin-Lof type theory. Each truncated version of this model can be carried out internally in dependent type theory, and we have formalized the first truncated level, which is enough to represent isomorphisms of algebraic structure as equality.
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34.
  • Barro, Lassina, et al. (författare)
  • A double-virally-inactivated (Intercept-solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells
  • 2019
  • Ingår i: Transfusion. - : John Wiley & Sons. - 0041-1132 .- 1537-2995. ; 59:6, s. 2061-2073
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno-free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a double-virally-inactivated HPL (DVI-HPL) prepared from expired Intercept-treated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be used for MSC expansion. STUDY DESIGN AND METHODS Expired Intercept-treated PCs in 65% platelet (PLT) additive solution were pooled and subjected to a 1% tri-n-butyl phosphate/1% Triton X-45 treatment followed by soybean oil, hydrophobic interaction chromatography purification, and sterile filtration. Bone marrow-derived MSCs (BM-MSCs) were expanded for four passages in growth medium containing 10% DVI-HPL, I-HPL (from Intercept-PC only), untreated HPL, and FBS. MSC morphology, doubling time, immunophenotype, immunosuppressive activity, and differentiation capacity were compared. RESULTS Expanded cells had typical spindle morphology and showed higher viability in all HPL conditions than in FBS. The DVI-HPL and FBS-expanded cells were morphologically larger than in I-HPL and HPL supplements. The cumulative population doubling was lower using DVI-HPL than with HPL and I-HPL, but significantly higher than using FBS. Immunophenotype was not affected by the supplements used. Immunosuppressive activity was maintained with all supplements. Differentiation capacity into chondrocytes and osteocytes was more effective in DVI-HPL but less toward adipocytes compared to other supplements. CONCLUSIONS Human PLT lysate made from Intercept-PCs subjected to S/D treatment may be an alternative to untreated HPL and to I-HPL for BM-MSC expansion. This finding reinforces the potential of HPL as a virally safe alternative to FBS for clinical grade MSC expansion protocols.
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35.
  • Barro, Lassina, et al. (författare)
  • Nanofiltration of growth media supplemented with human platelet lysates for pathogen-safe xeno-free expansion of mesenchymal stromal cells
  • 2020
  • Ingår i: Cytotherapy. - : Elsevier BV. - 1465-3249 .- 1477-2566. ; 22:8, s. 458-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Background aims: Human platelet lysate can replace fetal bovine serum (FBS) for xeno-free ex vivo expansion of mesenchymal stromal cells (MSCs), but pooling of platelet concentrates (PCs) increases risks of pathogen transmission. We evaluated the feasibility of performing nanofiltration of platelet lysates and determined the impact on expansion of bone marrow-derived MSCs. Methods: Platelet lysates were prepared by freeze-thawing of pathogen-reduced (Intercept) PCs suspended in 65% storage solution (SPP+) and 35% plasma, and by serum-conversion of PCs suspended in 100% plasma. Lysates were added to the MSC growth media at 10% (v/v), filtered and subjected to cascade nanofiltration on 35- and 19-nm Planova filters. Media supplemented with 10% starting platelet lysates or FBS were used as the controls. Impacts of nanofiltration on the growth media composition, removal of platelet extracellular vesicles (PEVs) and MSC expansion were evaluated. Results: Nanofiltration did not detrimentally affect contents of total protein and growth factors or the biochemical composition. The clearance factor of PEVs was >3 log values. Expansion, proliferation, membranemarkers, differentiation potential and immunosuppressive properties of cells in nanofiltered media were consistently better than those expanded in FBS-supplemented media. Compared with FBS, chondrogenesis and osteogenesis genes were expressed more in nanofiltered media, and there were fewer senescent cells over six passages. Conclusions: Nanofiltration of growth media supplemented with two types of platelet lysates, including one prepared from pathogen-reduced PCs, is technically feasible. These data support the possibility of developing pathogen-reduced xeno-free growth media for clinical-grade propagation of human cells.
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36.
  • Becker, Johan, et al. (författare)
  • Atmospheric corrosion of silver, copper and nickel exposed to hydrogen sulphide : a multi-analytical investigation approach
  • 2022
  • Ingår i: Corrosion Science. - : Elsevier Ltd. - 0010-938X .- 1879-0496. ; 209
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of two concentrations of H2S (0.5 and 2.5 ppm), in controlled laboratory conditions (20 °C, 75%RH), on the atmospheric corrosion of pure Ag, Cu and Ni was investigated in this study. The corrosion product morphology and composition were analysed through a multi-technique approach including SEM/EDX, Raman spectroscopy, XPS and XRD. Different corrosion products were identified depending on the type of characterisations providing a better overview of the effect of H2S on the atmospheric corrosion of pure Ag, Cu and Ni. Possible mechanisms involved in the formation of these corrosion products are also discussed in this work. © 2022 The Authors
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37.
  • Bruins, Harman M, et al. (författare)
  • The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer : a systematic review
  • 2014
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 66:6, s. 1065-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.
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38.
  • Cassagne, Thierry B., et al. (författare)
  • An update on the use of duplex stainless steels in sour environments
  • 2012
  • Ingår i: NACE - International Corrosion Conference Series. - 9781622760787 ; , s. 3041-3055
  • Konferensbidrag (refereegranskat)abstract
    • Since the early days of production of the Lacq sour field in the South West of France, where early duplex stainless steel grades were used on wellheads and valves these alloys have been used extensively in the upstream Oil and Gas industry for sour applications. It is known that these alloys have a limited resistance in H 2S containing production environments as given in the NACE MR0175/ISO 15156 Standard. However these limits are conservative because they consider a low pH and high chloride content at the same time, a situation rarely encountered in service. Temperature is an additional parameter with a complex influence which may depend on the other parameters. This topic is not new and several literature reviews have already been published on this subject over the years. Unlike these past reviews this paper aims at summarizing the sulfide stress cracking and stress corrosion cracking resistance of commonly used duplex stainless steels in sour media under more relevant and realistic operating conditions. The goal is to give an overview of the latest available knowledge on the subject including selected relevant literature data, service experience and new laboratory data.
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39.
  • Cassagne, Thierry B., et al. (författare)
  • Replacing titanium in sea water plate heat exchangers
  • 2010
  • Ingår i: NACE - International Corrosion Conference Series.
  • Konferensbidrag (refereegranskat)abstract
    • The use of titanium plate heat exchangers is widespread for Offshore and Coastal installations where seawater cooling is required. Several years ago difficulties to supply titanium Grade 1 for this application triggered the need for qualification of other alloys for this application. Applications using passive alloys are especially susceptible to crevice corrosion when exposed to hot seawater. Since titanium is the most corrosion resistant alloy in seawater only highly corrosion resistant alloys could be considered for its replacement in plate heat exchangers. In addition since they need to be shaped into plates by cold pressing only alloys with a high formability could be selected. This narrowed even further candidate alloys for plate heat exchangers. In this study nickel chromium molybdenum alloys and a highly alloyed stainless steel were tested between 30 and 70°C in natural seawater with up to 1 ppm free chlorine. Rather than using short term electrochemical testing that is often difficult to compare with service performance long term exposure tests (up to 18 months) of real plate heat exchangers were carried out. These tests are considered to be more representative of actual service conditions. The results of these tests and their significance are discussed and compared with previous reported work.
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40.
  • Coomans, Marijke, et al. (författare)
  • Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period
  • 2022
  • Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:12, s. 2159-2169
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Maintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period. Methods We included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period. Results Five thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9-29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on >= 1 scale. Median deterioration-free survival period ranged between 3.8-5.4 months, and median time-to-deterioration between 8.2-11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period. Conclusions HRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled.
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41.
  • Coomans, Marijke, et al. (författare)
  • The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials
  • 2019
  • Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 116, s. 190-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.
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42.
  • Coquand, Thierry, 1961, et al. (författare)
  • THE INDEPENDENCE OF MARKOV'S PRINCIPLE IN TYPE THEORY
  • 2017
  • Ingår i: Logical Methods in Computer Science. - 1860-5974. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we show that Markov's principle is not derivable in dependent type theory with natural numbers and one universe. One way to prove this would be to remark that Markov's principle does not hold in a sheaf model of type theory over Cantor space, since Markov's principle does not hold for the generic point of this model [CMR17]. Instead we design an extension of type theory, which intuitively extends type theory by the addition of a generic point of Cantor space. We then show the consistency of this extension by a normalization argument. Markov's principle does not hold in this extension, and it follows that it cannot be proved in type theory.
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43.
  •  
44.
  • Depienne, Christel, et al. (författare)
  • Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU
  • 2017
  • Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 136:4, s. 463-479
  • Tidskriftsartikel (refereegranskat)abstract
    • Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.
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45.
  • Diler, Erwan, et al. (författare)
  • Characterization of corrosion products of Zn and Zn-Mg-Al coated steel in a marine atmosphere
  • 2014
  • Ingår i: Corrosion Science. - : Elsevier Ltd. - 0010-938X .- 1879-0496. ; 87, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • The corrosion behaviour of pure zinc and zinc-magnesium-aluminium alloy (ZMA) has been studied during 6months of exposure in marine environment (Brest, France). The composition of corrosion products is analysed using infrared spectroscopy (FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). An improved corrosion resistance of ZMA is observed. This improvement is found to be connected to Mg2+ and Al3+ induced quenching of corrosion activity and to the enhancement of NaZn4Cl(OH)6SO4·6H2O in the formed corrosion product.
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46.
  • Diler, Erwan, et al. (författare)
  • Chemistry of corrosion products of Zn and MgZn pure phases under atmospheric conditions
  • 2012
  • Ingår i: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 65, s. 178-186
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a corrosion behaviour study of pure phases of zinc and zinc-magnesium contaminated with NaCl and exposed to humid air for 30days: Zn, Mg 2Zn 11 and MgZn 2. The composition of corrosion products is analysed using infrared spectroscopy (FTIR), X-ray diffraction (XRD), ion chromatography (IC), and X-ray photoelectron spectroscopy (XPS). The improved corrosion stability of MgZn 2 is found to be connected to changes in the surface pH and to the nature of the formed corrosion products. The presence of magnesium modifies the proportion of the OH and CO 3 bonds in the corroded products. This explains the improvement in corrosion resistance.
  •  
47.
  • Diler, Erwan, et al. (författare)
  • Initial formation of corrosion products on pure zinc and MgZn2 examinated by XPS
  • 2014
  • Ingår i: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 79, s. 83-88
  • Tidskriftsartikel (refereegranskat)abstract
    • A corrosion behaviour study of pure phases of zinc and zinc-magnesium (MgZn2) exposed to humid air at 35°C for 4days is presented. For zinc, hydroxide formation at the surface and zinc oxide in the first innerlayers is observed. The corrosion of the MgZn2 leads to the segregation of magnesium at the surface to mainly form magnesium hydroxycarbonate: the presence of magnesium modifies the corrosion products. At larger depths, metallic zinc coexists with magnesium oxide and hydrozincite. The higher reactivity of MgZn2 alloy can be attributed to the interaction with carbonate ions.
  •  
48.
  • Diler, Erwan, et al. (författare)
  • Stability of ZnMgO oxide in a weak alkaline solution
  • 2012
  • Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 520:7, s. 2819-2823
  • Tidskriftsartikel (refereegranskat)abstract
    • Zinc oxide (ZnO) is a chemical compound of great interest used, for example, as photocatalyst in the purification of wastewater or polluted air. However, neither dissolution, nor photo-dissolution of ZnO is negligible: indeed, both processes reduce significantly the efficiency of photocatalysis and then lead to a secondary pollution by free Zn 2 +. In the present study, the stability of ZnMgO thin films in weak alkaline solution is investigated. We demonstrate that the replacement of Zn 2 + ion with Mg 2 + ion results in the production of a Zn 0.84Mg 0.16O solid solution, whose stability is higher than that of the ZnO sample. This alloy, thus, constitutes an alternative to the use of ZnO in photocatalysis applications. To gain more insights into the higher resistance of such alloys to the dissolution process, X-Ray photoelectron spectroscopy measurements were performed. They highlighted the role of OH group adsorption in the experimentally observed enhancement of ZnMgO stability.
  •  
49.
  • El Masri, I., et al. (författare)
  • Development of a RFID sensitive tag dedicated to the monitoring of the environmental corrosiveness for indoor applications
  • 2020
  • Ingår i: Sensors and actuators. B, Chemical. - : Elsevier B.V.. - 0925-4005 .- 1873-3077. ; 322
  • Tidskriftsartikel (refereegranskat)abstract
    • The environmental corrosiveness is governed for indoor applications by the presence of gaseous pollutants in air and levels of temperature and relative humidity. Its determination is a challenging task and requires the monitoring of thickness reduction of selected metals in the range of few tens of nanometers. The present work aims at developing an UHF RFID (Ultra High Frequency Radio Frequency Identification) sensor dedicated to such measurements. The sensor is based on the coupling between the antenna of a commercial RFID tag and a thin layer of copper exposed to the environment. The ability of the proposed sensor to be sensitive to a variation of the metal thickness in the range of tens of nanometers is demonstrated experimentally through exposure tests in a climatic chamber. The results are supported by electromagnetic simulations performed in the case of a coupling between a dipolar antenna and a thin metallic layer.
  •  
50.
  • Feltre, Anna, et al. (författare)
  • The MUSE Hubble Ultra Deep Field Survey XII. Mg II emission and absorption in star-forming galaxies
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
  • Tidskriftsartikel (refereegranskat)abstract
    • The physical origin of the near-ultraviolet Mg II emission remains an underexplored domain, unlike more typical emission lines that are detected in the spectra of star-forming galaxies. We explore the nebular and physical properties of a sample of 381 galaxies between 0.70 < z < 2.34 drawn from the MUSE Hubble Ultra Deep Survey. The spectra of these galaxies show a wide variety of profiles of the Mg II lambda lambda 2796, 2803 resonant doublet, from absorption to emission. We present a study on the main drivers for the detection of Mg II emission in galaxy spectra. By exploiting photoionization models, we verified that the emission-line ratios observed in galaxies with Mg II in emission are consistent with nebular emission from HII regions. From a simultaneous analysis of MUSE spectra and ancillary Hubble Space Telescope information through spectral energy distribution fitting, we find that galaxies with Mg II in emission have lower stellar masses, smaller sizes, bluer spectral slopes, and lower optical depth than those with absorption. This leads us to suggest that Mg II emission is a potential tracer of physical conditions that are not merely related to those of the ionized gas. We show that these differences in Mg II emission and absorption can be explained in terms of a higher dust and neutral gas content in the interstellar medium (ISM) of galaxies showing Mg II in absorption, which confirms the extreme sensitivity of Mg II to the presence of the neutral ISM. We conclude with an analogy between the Mg II doublet and the Ly alpha line that lies in their resonant nature. Further investigations with current and future facilities, including the James Webb Space Telescope, are promising because the detection of Mg II emission and its potential connection with Ly alpha could provide new insights into the ISM content in the early Universe.
  •  
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