| 1. |
- Engert, Andreas, et al.
(författare)
-
The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
-
Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
-
Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
|
|
| 2. |
- Aben, Ralf C. H., et al.
(författare)
-
Cross continental increase in methane ebullition under climate change
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Methane (CH4) strongly contributes to observed global warming. As natural CH4 emissions mainly originate from wet ecosystems, it is important to unravel how climate change may affect these emissions. This is especially true for ebullition (bubble flux from sediments), a pathway that has long been underestimated but generally dominates emissions. Here we show a remarkably strong relationship between CH4 ebullition and temperature across a wide range of freshwater ecosystems on different continents using multi-seasonal CH4 ebullition data from the literature. As these temperature-ebullition relationships may have been affected by seasonal variation in organic matter availability, we also conducted a controlled year-round mesocosm experiment. Here 4 degrees C warming led to 51% higher total annual CH4 ebullition, while diffusion was not affected. Our combined findings suggest that global warming will strongly enhance freshwater CH4 emissions through a disproportional increase in ebullition (6-20% per 1 degrees C increase), contributing to global warming.
|
|
| 3. |
|
|
| 4. |
- Badian, Reza A., et al.
(författare)
-
Wide-field mosaics of the corneal subbasal nerve plexus in Parkinsons disease using in vivo confocal microscopy
- 2021
-
Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- In vivo confocal microscopy (IVCM) is a non-invasive imaging technique facilitating real-time acquisition of images from the live cornea and its layers with high resolution (1-2 mu m) and high magnification (600 to 800-fold). IVCM is extensively used to examine the cornea at a cellular level, including the subbasal nerve plexus (SBNP). IVCM of the cornea has thus gained intense interest for probing ophthalmic and systemic diseases affecting peripheral nerves. One of the main drawbacks, however, is the small field of view of IVCM, preventing an overview of SBNP architecture and necessitating subjective image sampling of small areas of the SBNP for analysis. Here, we provide a high-quality dataset of the corneal SBNP reconstructed by automated mosaicking, with an average mosaic image size corresponding to 48 individual IVCM fields of view. The mosaic dataset represents a group of 42 individuals with Parkinsons disease (PD) with and without concurrent restless leg syndrome. Additionally, mosaics from a control group (n = 13) without PD are also provided, along with clinical data for all included participants.
|
|
| 5. |
- Fiehn, Anne-Marie Kanstrup, et al.
(författare)
-
Distribution of histopathological features along the colon in microscopic colitis
- 2021
-
Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 36, s. 151-159
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. Methods Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. Results In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. Conclusion Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.
|
|
| 6. |
|
|
| 7. |
- Greite, Robert, et al.
(författare)
-
Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion
- 2022
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:21
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.
|
|
| 8. |
- Greite, Robert, et al.
(författare)
-
Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia
- 2023
-
Ingår i: Clinical and Translational Science. - 1752-8054. ; 16:12, s. 2729-2743
-
Tidskriftsartikel (refereegranskat)abstract
- Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.
|
|
| 9. |
- Hagendorff, Andreas, et al.
(författare)
-
Manual on indications and performance of echocardiography-Update 2020 of the German Cardiac Society
- 2020
-
Ingår i: KARDIOLOGE. - : SPRINGER HEIDELBERG. - 1864-9718 .- 1864-9726. ; 14:5, s. 396-431
-
Tidskriftsartikel (refereegranskat)abstract
- The new manual on indications for and performance of echocardiography focuses primarily on the transthoracic echocardiographic approach. The performance of a standardized documentation in transthoracic echocardiography includes the acquisition of several cineloops and Doppler spectra with consecutive measurements illustrated by figures and a scheme of an echocardiographic report. The extended documentation in transthoracic echocardiography is presented with respect to specific pathological alterations of the heart. This includes alterations of the left ventricular wall thickness, the global and regional reduction of left ventricular function, diastolic dysfunction with normal left ventricular systolic function, pressure and volume overload of the right ventricle and the reduction of right ventricular function and pathological alterations of the heart valves. Echocardiography performed in the presence of aortic valve stenosis and regurgitation, mitral valve stenosis and regurgitation, tricuspid valve regurgitation as well as less common heart valve diseases and endocarditis is presented in special sections. The manual ends with sections describing additional echocardiographic modalities, the reporting and the use of emergency echocardiography.
|
|
| 10. |
- Hauber, Ernst, et al.
(författare)
-
Landscape evolution in Martian mid-latitude regions: Insights from analogous periglacial landforms in Svalbard.
- 2011
-
Ingår i: Geological Society, London, Special Publications. ; 356, s. 111-131
-
Tidskriftsartikel (refereegranskat)abstract
- Periglacial landforms on Spitsbergen (Svalbard, Norway) are morphologically similar to landforms on Mars that are probably related to the past and/or present existence of ice at or near the surface. Many of these landforms, such as gullies, debris-flow fans, polygonal terrain, fractured mounds and rock-glacier-like features, are observed in close spatial proximity in mid-latitude craters on Mars. On Svalbard, analogous landforms occur in strikingly similar proximity, which makes them useful study cases to infer the spatial and chronological evolution of Martian coldclimate surface processes. The analysis of the morphological inventory of analogous landforms on Svalbard and Mars allows the processes operating on Mars to be constrained. Different qualitative scenarios of landscape evolution on Mars help to better understand the action of periglacial processes on Mars in the recent past.
|
|
| 11. |
- Hess, Timo, et al.
(författare)
-
Dissecting the genetic heterogeneity of gastric cancer
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
|
|
| 12. |
- Karagiannidis, Christian, et al.
(författare)
-
Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis
- 2017
-
Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m2. The present study in an animal model with similar CO2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO2R.METHODS: Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m2 were used to perform vv-ECCO2R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min.RESULTS: Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m2. Maximal CO2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m2). The membrane lung with a surface of 0.4 m2 allowed a maximum CO2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m2 did not result in substantially higher CO2 elimination rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg) in the largest membrane lung, whereas the smallest revealed a pressure drop of more than 50 mmHg with 1000 ml blood flow/min.CONCLUSIONS: In this porcine model, vv-ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m2. In contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely correct severe respiratory acidosis, irrespective of the surface area of the membrane lung being used. The converse was also true, low surface membrane lungs (0.4 m2) were not capable of completely correcting severe respiratory acidosis across the range of blood flows used in this study.
|
|
| 13. |
- 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)
|
|
| 14. |
- Kirchhof, Paulus, et al.
(författare)
-
A roadmap to improve the quality of atrial fibrillation management : proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference
- 2016
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:1, s. 37-50
-
Tidskriftsartikel (refereegranskat)abstract
- At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.
|
|
| 15. |
- Kirchhof, Paulus, et al.
(författare)
-
Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
-
Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
|
|
| 16. |
- Kirchhof, Paulus, et al.
(författare)
-
Personalized management of atrial fibrillation : Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference
- 2013
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:11, s. 1540-1556
-
Tidskriftsartikel (refereegranskat)abstract
- The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.
|
|
| 17. |
|
|
| 18. |
- Kulka, Ulrike, et al.
(författare)
-
RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry
- 2017
-
Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 93:1, s. 2-14
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.
|
|
| 19. |
- Löhr, Johannes-Matthias, et al.
(författare)
-
Outcome of probe-based confocal laser endomicroscopy (pCLE) during endoscopic retrograde cholangiopancreatography : a single-center prospective study in 45 patients.
- 2015
-
Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 3:6, s. 551-560
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC).AIMS: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP).METHODS: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year.RESULTS: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred.CONCLUSIONS: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer.
|
|
| 20. |
- Münch, Andreas, et al.
(författare)
-
Budesonide as induction therapy for incomplete microscopic colitis : A randomised, placebo-controlled multicentre trial
- 2021
-
Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 9:7, s. 837-847
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi.Methods: Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8.Results: Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase.Conclusions: Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.
|
|
| 21. |
- Münch, Andreas, et al.
(författare)
-
Smoking Status Influences Clinical Outcome in Collagenous Colitis
- 2016
-
Ingår i: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Oxford University Press. - 1873-9946 .- 1876-4479. ; 10:4, s. 449-454
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known.Methods: In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model.Results: Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome.Conclusion: Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.
|
|
| 22. |
- Neiman, Maja, et al.
(författare)
-
Plasma Profiling Reveals Human Fibulin-1 as Candidate Marker for Renal Impairment
- 2011
-
Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 10:11, s. 4925-4934
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for reliable and sensitive biomarkers for renal impairments to detect early signs of kidney toxicity and to monitor progression of disease. Here, antibody suspension bead arrays were applied to profile plasma samples from patients with four types of kidney disorders: glomerulonephritis, diabetic nephropathy, obstructive uropathy, and analgesic abuse. In total, 200 clinical renal-associated cases and control plasma samples from different cohorts were profiled. Parallel plasma protein profiles were obtained using biotinylated and nonfractionated samples and a selected set of 94 proteins targeted by 129 antigen-purified polyclonal antibodies. Out of the analyzed target proteins, human fibulin-1 was detected at significantly higher levels in the glomerulonephritis patient group compared to the controls and with elevated levels in patient samples for all other renal disorders investigated. Two polyclonal antibodies and one monoclonal antibody directed toward separate, nonoverlapping epitopes showed the same trend in the discovery cohorts. A technical verification using Western blot analysis of selected patient plasma confirmed the trends toward higher abundance of the target protein in disease samples. Furthermore, a verification study was carried out in the context of glomerulonephritis using an independent case and control cohort, and this confirmed the results from the discovery cohort, suggesting that plasma levels of fibulin-1 could serve as a potential indicator to monitor kidney malfunction or kidney damage.
|
|
| 23. |
- Ostaszewski, Marek, et al.
(författare)
-
COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
-
Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
-
Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
|
|
| 24. |
- Otto, Katharina, et al.
(författare)
-
MASCOT’s in situ analysis of asteroid Ryugu in the context of regolith samples and remote sensing data returned by Hayabusa2
- 2023
-
Ingår i: Earth Planets and Space. - : Springer. - 1343-8832 .- 1880-5981. ; 75:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Hayabusa2 mission provided a unique data set of asteroid Ryugu that covers a wide range of spatial scale from the orbiter remote sensing instruments to the returned samples. The MASCOT lander that was delivered onto the surface of Ryugu aimed to provide context for these data sets by producing in situ data collected by a camera (MasCam), a radiometer (MARA), a magnetometer (MasMag) and a spectrometer (MicrOmega). In this work, we evaluate the success of MASCOT as an integrated lander to bridge the gap between orbiter and returned sample analysis. We find that MASCOT’s measurements and derivatives thereof, including the rock morphology, colour in the visible wavelengths, possible meteorite analogue, density, and porosity of the rock at the landing site are in good agreement with those of the orbiter and the returned samples. However, it also provides information on the spatial scale (sub-millimetres to centimetres) at which some physical properties such as the thermal inertia and reflectance undergo scale-dependent changes. Some of the in situ observations such as the presence of clast/inclusions in rocks and the absence of fine particles at the landing site was uniquely identified by MASCOT. Thus, we conclude that the delivery of an in situ instrument like MASCOT provides a valuable data set that complements and provides context for remote sensing and returned sample analyses.
|
|
| 25. |
- Pérez-Alonso, Marta-Marina, et al.
(författare)
-
The calcium sensor CBL7 is required for Serendipita indica-induced growth stimulation in Arabidopsis thaliana, controlling defense against the endophyte and K+ homoeostasis in the symbiosis
- 2022
-
Ingår i: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 45:11, s. 3367-3382
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium is an important second messenger in plants. The activation of Ca2+ signalling cascades is critical in the activation of adaptive processes in response to environmental stimuli. Root colonization by the growth promoting endophyte Serendipita indica involves the increase of cytosolic Ca2+ levels in Arabidopsis thaliana. Here, we investigated transcriptional changes in Arabidopsis roots during symbiosis with S. indica. RNA-seq profiling disclosed the induction of Calcineurin B-like 7 (CBL7) during early and later phases of the interaction. Consistently, reverse genetic evidence highlighted the functional relevance of CBL7 and tested the involvement of a CBL7-CBL-interacting protein kinase 13 signalling pathway. The loss-of-function of CBL7 abolished the growth promoting effect and affected root colonization. The transcriptomics analysis of cbl7 revealed the involvement of this Ca2+ sensor in activating plant defense responses. Furthermore, we report on the contribution of CBL7 to potassium transport in Arabidopsis. We analysed K+ contents in wild-type and cbl7 plants and observed a significant increase of K+ in roots of cbl7 plants, while shoot tissues demonstrated K+ depletion. Taken together, our work associates CBL7 with an important role in the mutual interaction between Arabidopsis and S. indica and links CBL7 to K+ transport.
|
|
| 26. |
- Reck, Kristian A., et al.
(författare)
-
Early-stage silver growth during sputter deposition on SiO2 and polystyrene - Comparison of biased DC magnetron sputtering, high-power impulse magnetron sputtering (HiPIMS) and bipolar HiPIMS
- 2024
-
Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 666
-
Tidskriftsartikel (refereegranskat)abstract
- The integration of silver thin films into optoelectronic devices has gained much interest due to their exceptional properties in terms of conductivity and compatibility with flexible substrates. For this type of application, ultrathin layers are desirable, because of their optical transparency. Standard direct current magnetron sputtering (DCMS) is known to lead to undesirable formation of islands at low effective film thicknesses on typical substrates like SiO2 or polystyrene (PS). Therefore, in this study, we explore high-power impulse magnetron sputtering (HiPIMS) with optional further acceleration of metal ions by biasing the substrate or an additional positive pulse (bipolar HiPIMS) for the fabrication of ultra-thin silver layers. The morphology and electrical properties of ultra-thin silver layers with selected effective thicknesses are characterized on SiO2 and PS substrates. The growth evolution of characteristic parameters is further investigated by in-situ grazing-incidence small-angle Xray scattering (GISAXS). The results show that HiPIMS deposition yields films with a higher density of clusters than DCMS leading to a percolation threshold at lower effective film thicknesses. This effect is amplified by further ion acceleration. Thus, we suggest HiPIMS as a promising technique for fabricating ultra-thin, conductive layers on organic and oxide substrates.
|
|
| 27. |
- Rodriguez, Sébastien, et al.
(författare)
-
Science goals and new mission concepts for future exploration of Titan's atmosphere, geology and habitability : titan POlar scout/orbitEr and in situ lake lander and DrONe explorer (POSEIDON)
- 2022
-
Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 911-973
-
Tidskriftsartikel (refereegranskat)abstract
- In response to ESA’s “Voyage 2050” announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn’s largest moon Titan. Titan, a “world with two oceans”, is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan’s remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a “heavy” drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan’s northern latitudes with an orbiter and in situ element(s) would be highly complementary in terms of timing (with possible mission timing overlap), locations, and science goals with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan’s equatorial regions, in the mid-2030s.
|
|
| 28. |
- Ryghaug, Marianne, et al.
(författare)
-
A Social Sciences and Humanities research agenda for transport and mobility in Europe : key themes and 100 research questions
- 2023
-
Ingår i: Transport Reviews. - : Informa UK Limited. - 0144-1647 .- 1464-5327. ; 43:4, s. 755-779
-
Tidskriftsartikel (refereegranskat)abstract
- Transport and mobility systems need to be transformed to meet climate change goals and reduce negative environmental and social effects. Despite EU policies having targeted such problems for more than three decades, transitions have been slow and geographically uneven. For effective change to happen, transport and mobility research needs fresh perspectives and better integration of knowledge from the Social Sciences and Humanities. Based on a Horizon Scanning approach, which allowed for a great deal of openness and variety in scholarly viewpoints, this paper presents a novel research agenda consisting of 8 themes and 100 research questions that may contribute to achieving environmentally sustainable mobility transitions within Europe. This research agenda highlights the need to not only support technological solutions for low-carbon mobility, but the importance of transformative policies that include new processes of knowledge production, civic participation and epistemic justice. We contend that the agenda points to the need for further research on the dynamics of science-society interactions.
|
|
| 29. |
- Sahamkhadam, Maziar, et al.
(författare)
-
Copula-based Black-Litterman portfolio optimization
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We extend the Black-Litterman (BL) approach to incorporate tail dependency in portfolio optimization and estimate the posterior joint distribution of returns using vine copulas. Our novel copula-based BL (CBL) model leads to flexibility in modeling returns symmetric and asymmetric multivariate distribution from a range of copula families. Based on a sample of 30 stocks, we evaluate the performance of the suggested CBL approach and portfolio optimization technique using out-of-sample back-testing. Our empirical analysis and robustness check indicate better performance for the CBL portfolios in terms of lower tail risk and higher risk-adjusted returns, compared to the benchmark strategies.
|
|
| 30. |
- Sahamkhadam, Maziar, et al.
(författare)
-
Copula-based Black–Litterman portfolio optimization
- 2022
-
Ingår i: European Journal of Operational Research. - : Elsevier. - 0377-2217 .- 1872-6860. ; 297:3, s. 1055-1070
-
Tidskriftsartikel (refereegranskat)abstract
- We extend the Black-Litterman (BL) approach to incorporate tail dependency in portfolio optimization and estimate the posterior joint distribution of returns using vine copulas. Our novel copula-based BL (CBL) model leads to flexibility in modeling returns symmetric and asymmetric multivariate distribution from a range of copula families. Based on a sample of the Eurostoxx 50 constituents (also for S&P 100 as robustness check), we evaluate the performance of the suggested CBL approach and portfolio optimization technique using out-of-sample back-testing. Our empirical analysis and robustness check indicate better performance for the CBL portfolios in terms of lower tail risk and higher risk-adjusted returns, compared to the benchmark strategies.
|
|
| 31. |
- Sahamkhadam, Maziar, et al.
(författare)
-
Portfolio optimization based on GARCH-EVT-Copula forecasting models
- 2018
-
Ingår i: International Journal of Forecasting. - : Elsevier. - 0169-2070 .- 1872-8200. ; 34:3, s. 497-506
-
Tidskriftsartikel (refereegranskat)abstract
- This study uses GARCH-EVT-copula and ARMA-GARCH-EVT-copula models to perform out-of-sample forecasts and simulate one-day-ahead returns for ten stock indexes. We construct optimal portfolios based on the global minimum variance (GMV), minimum conditional value-at-risk (Min-CVaR) and certainty equivalence tangency (CET) criteria, and model the dependence structure between stock market returns by employing elliptical (Student-t and Gaussian) and Archimedean (Clayton, Frank and Gumbel) copulas. We analyze the performances of 288 risk modeling portfolio strategies using out-of-sample back-testing. Our main finding is that the CET portfolio, based on ARMA-GARCH-EVT-copula forecasts, outperforms the benchmark portfolio based on historical returns. The regression analyses show that GARCH-EVT forecasting models, which use Gaussian or Student-t copulas, are best at reducing the portfolio risk. (C) 2018 International Institute of Forecasters. Published by Elsevier B.V. All rights reserved.
|
|
| 32. |
- Schnabel, Renate B, et al.
(författare)
-
Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation : the 8th AFNET/EHRA consensus conference
- 2023
-
Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 6-27
-
Tidskriftsartikel (refereegranskat)abstract
- Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
|
|
| 33. |
- Scholz, Joachim, et al.
(författare)
-
The IASP classification of chronic pain for ICD-11 : chronic neuropathic pain.
- 2019
-
Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 160:1, s. 53-59
-
Tidskriftsartikel (refereegranskat)abstract
- The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.
|
|
| 34. |
- Schuette, Moritz, et al.
(författare)
-
Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
|
|
| 35. |
- Wittmann, Lutz, et al.
(författare)
-
Ein Traum, zwei Methoden : das Traumseminar nach Morgenthaler und das Zurich Dream Proces Coding System im Vergleich
- 2017
-
Ingår i: Journal für Psychoanalyse. - : JfP. - 1613-4702 .- 2297-878X. ; 58, s. 99-129
-
Tidskriftsartikel (refereegranskat)abstract
- Die vorliegende Arbeit will zwei bezüglich Zielsetzung und Methodik unterschiedliche Herangehensweisen zum Thema Traum miteinander vergleichen. Nach einer Vorstellung von zugrundeliegenden Annahmen und technischem Vorgehen wird derselbe Traumbericht einer Patientin unabhängig voneinander von einem Traumseminar nach Morgenthaler sowie dem Zurich Dream Process Coding System nach Moser und von Zeppelin untersucht. Die Analyseschritte werden von einer Fallvignette ergänzt und von der behandelnden Therapeutin kommentiert. Eine kritische und vergleichende Reflexion der beiden Ansätze schliesst den Aufsatz ab.
|
|
