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- Zaborowski, AM, et al.
(author)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Journal article (peer-reviewed)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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- Faatz, B., et al.
(author)
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Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
- 2016
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Journal article (peer-reviewed)abstract
- Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs-dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.
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- Omerovic, Elmir, 1968, et al.
(author)
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Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central role for catecholamines and sympathetic nervous system
- 2022
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:2, s. 257-273
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Journal article (peer-reviewed)abstract
- This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including beta-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model.
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| 18. |
- Ahrendt, Wolfgang, 1967, et al.
(author)
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The KeY platform for verification and analysis of java programs
- 2014
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 8471:8471, s. 55-71
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Conference paper (peer-reviewed)abstract
- The KeY system offers a platform of software analysis tools for sequential Java. Foremost, this includes full functional verification against contracts written in the Java Modeling Language. But the approach is general enough to provide a basis for other methods and purposes: (i) complementary validation techniques to formal verification such as testing and debugging, (ii) methods that reduce the complexity of verification such as modularization and abstract interpretation, (iii) analyses of non-functional properties such as information flowsecurity, and (iv) sound program transformation and code generation. We show that deductive technology that has been developed for full functional verification can be used as a basis and framework for other purposes than pure functional verification. We use the current release of the KeY system as an example to explain and prove this claim.
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- Bruns, S. B., et al.
(author)
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Reporting errors and biases in published empirical findings: Evidence from innovation research
- 2019
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In: Research Policy. - : Elsevier BV. - 0048-7333. ; 48:9
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Journal article (peer-reviewed)abstract
- Errors and biases in published results compromise the reliability of empirical research, posing threats to the cumulative research process and to evidence-based decision making. We provide evidence on reporting errors and biases in innovation research. We find that 45% of the articles in our sample contain at least one result for which the provided statistical information is not consistent with reported significance levels. In 25% of the articles, at least one strong reporting error is diagnosed where a statistically non-significant finding becomes significant or vice versa using the common significance threshold of 0.1. The error rate at the test level is very small with 4.0% exhibiting any error and 1.4% showing strong errors. We also find systematically more marginally significant findings compared to marginally non-significant findings at the 0.05 and 0.1 thresholds of statistical significance. These discontinuities indicate the presence of reporting biases. Explorative analysis suggests that discontinuities are related to authors’ affiliations and to a lesser extent the article's rank in the issue and the style of reporting. © 2019 Elsevier B.V.
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| 23. |
- Bruns, S., et al.
(author)
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On the material dependency of peri-implant morphology and stability in healing bone
- 2023
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In: Bioactive Materials. - : Elsevier. - 2452-199X. ; 28, s. 155-166
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Journal article (peer-reviewed)abstract
- The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 mu m resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.
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- Nilsson, K., et al.
(author)
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Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial
- 2023
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In: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:11, s. 1015-1024
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Journal article (peer-reviewed)abstract
- Background: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer.Patients and methods: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type.Results: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107).Conclusion: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.
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| 29. |
- Nilsson, Magnus, et al.
(author)
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Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed : The Study Protocol for the Randomized Controlled NEEDS Trial
- 2022
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In: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
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Journal article (peer-reviewed)abstract
- Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.
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| 30. |
- Omerovic, Elmir, 1968, et al.
(author)
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Pathophysiology of Takotsubo Syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 2: vascular pathophysiology, gender and sex hormones, genetics, chronic cardiovascular problems and clinical implications.
- 2022
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In: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 24:2, s. 274-286
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Journal article (peer-reviewed)abstract
- While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused the catecholamines and sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research. This article is protected by copyright. All rights reserved.
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| 31. |
- Scherer, SW, et al.
(author)
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Human chromosome 7: DNA sequence and biology
- 2003
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Journal article (peer-reviewed)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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