84 results on '"Häfner M"'
Search Results
2. Incorporation of Intracellular NanoSIMS Tracers to Oligonucleotide Conjugates via Strain Promoted Sydnone-Alkyne Cycloaddition.
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Lincy-Bianchi L, Häfner M, Becquart C, Tängemo C, Kurczy ME, Munier CC, and Knerr L
- Subjects
- Humans, Ligands, Acetylgalactosamine chemistry, Alkynes chemistry, Oligonucleotides chemistry, Cycloaddition Reaction methods
- Abstract
Extensive efforts have been dedicated to developing cell-specific targeting ligands that can be conjugated to therapeutic cargo, offering a promising yet still challenging strategy to deliver oligonucleotide therapeutics beyond the liver. Indeed, while the cargo and the ligand are crucial, the third component, the linker, is integral but is often overlooked. Here, we present strain-promoted sydnone-alkyne cycloaddition as a versatile linker chemistry for oligonucleotide synthesis, expanding the choices for bioconjugation of therapeutics while enabling subcellular detection of the linker and payload using nanoscale secondary ion mass spectrometry (NanoSIMS) imaging. This strategy was successfully applied to peptide and lipid ligands and profiled using the well characterized N -acetylgalactosamine (GalNAc) targeting ligand. The linker did not affect the expected activity of the conjugate and was detectable and distinguishable from the labeled cargo. Finally, this work not only offers a practical bioconjugation method but also enables the assessment of the linker's subcellular behavior, facilitating NanoSIMS imaging to monitor the three key components of therapeutic conjugates.
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- 2024
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3. Dressing up social psychology: Empirically investigating the psychological functions of clothing using the example of symbolic protection.
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Gruber R, Häfner M, and Kachel S
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- Male, Humans, Female, Clothing psychology, Ukraine, Psychology, Social, Bandages
- Abstract
Clothing behaviour remains an understudied research area within social psychology. Through the present research, we aim to anchor attire as an empirical research subject by investigating the psychological properties of one of its functionalities, namely, to provide protection. We argue that attire's undisputed role in shielding humans from environmental hazards may extend to the psychological level and protect them from the incorporeal consequences of existential threats symbolically. In this Registered Report, a mixed-methods approach links an ecologically valid field study of self-presentation in social media posts during Russia's war on Ukraine (Study 1; N = 248) with supraliminal priming of mortality salience in an online experiment (Study 2; N = 248). Across both studies, we expect that mortality concerns let people accentuate the physically protective attributes of clothing (e.g. more layers of clothing) and resort to more in-group prototypical dress styles (i.e. more gender-stereotypical). Findings show that people adjust their clothing preferences in response to existential threats, favouring in-group prototypical clothing (more gender-typical for both women and men in Study 1) and physically protective attire (higher in women and lower in men in Study 2) during high (vs. low) levels of existential threat. By positioning clothing as a research area within social psychology, our goal is to stimulate a wave of research on its profound role for humankind. Furthermore, we provide a dynamic and robust methodological approach to researching terror management theory., (© 2023 The Authors. British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)
- Published
- 2024
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4. Commentary.
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Haslach-Häfner M and Mönkemüller K
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2024
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5. Reading capsule endoscopy: Why not AI alone?
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Haslach-Häfner M and Mönkemüller K
- Abstract
Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.
- Published
- 2023
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6. Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.
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Messmann H, Bisschops R, Antonelli G, Libânio D, Sinonquel P, Abdelrahim M, Ahmad OF, Areia M, Bergman JJGHM, Bhandari P, Boskoski I, Dekker E, Domagk D, Ebigbo A, Eelbode T, Eliakim R, Häfner M, Haidry RJ, Jover R, Kaminski MF, Kuvaev R, Mori Y, Palazzo M, Repici A, Rondonotti E, Rutter MD, Saito Y, Sharma P, Spada C, Spadaccini M, Veitch A, Gralnek IM, Hassan C, and Dinis-Ribeiro M
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- Humans, Artificial Intelligence, Endoscopy, Gastrointestinal methods, Endoscopy, Digestive System, Endoscopy, Capsule Endoscopy, Precancerous Conditions, Gastrointestinal Diseases
- Abstract
This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection., Competing Interests: O.F. Ahmad has received speaker fees from Olympus (March 2022). G. Antonelli has received a consultancy fee from Medtronic. P. Bhandari’s department has received research grants from NEC Japan (June 2019, ongoing) and Fujifilm Europe (June 2020, ongoing). J.J.G.H.M. Bergman has received support for AI-related research in endoscopy from Olympus and and Fuijfilm; he has carried out sponsored AI-related research into Barrett’s esophagus for which the rights have been transferred to Olympus. R. Bisschops has received consultancy and speaker’s fees from Fujifilm, Pentax, and Medtronic (2015, ongoing), and provided consultancy to CDx Diagnostics (2017–2019); his department has received research grants from Pentax and Fujifilm (2015, ongoing), and from Medtronic (2018, ongoing). E. Dekker has received honoraria for consultancy from Fujifilm, Olympus, GI Supply, and PAION; she has received speakerʼs fees from Norgine, Ipsen, PAION, and Fujifilm. M. Dinis-Ribeiro has provided consultancy to Medtronic and Roche (2021–2022); his department has received support (loan for research) from Fujifilm (2021–2022); he is Co-Editor-in-Chief of Endoscopy journal. R. Eliakim has provided consultancy on various occasions to Medtronic (from 2019). I. Gralnek has provided consultancy to and been on the advisory board of Motus GI; he has provided consultancy to Boston Scientific, Clexio Biosciences, Medtronic, and Symbionix; he has received research support from Astra Zeneca and CheckCap; all during the last 3 years, 2019 to present. R.J. Haidry has received an educational grant to support research from Cook Endoscopy (2015, ongoing); his department has received an educational grant to support research from Medtronic (2018, ongoing). C. Hassan has received consulting fees and/or research grants from Alphasigma, Fujifilm, Medtronic, Norgine, Olympus, and Pentax. R. Joverʼs department has received a research grant from Medtronic (2021–2022). M.F. Kaminski has provided consultancy to Olympus (2016, ongoing) and Erbe (2021, ongoing), and has lectured for Boston Scientific (2016, ongoing) and Recordati (2020, ongoing). H. Messmann’s department has received financial and/or research support from Apollo Endosurgery, Biogen, Boston Scientific, CDx Diagnostics, Cook Medical, CSL Behring, Dr. Falk Pharma, Endo Tools Therapeutics, Erbe, Fujifilm, Hitachi, Janssen-Cilag, Medwork, Norgine, Nutricia, Olympus, Ovesco Endoscopy, Satisfai, Servier Deutschland, and US Endoscopy (in the past 3 years). Y. Mori has provided consultancy to and delivered talks for Olympus (2018–2022); he has ownership interest in Cybernet System Corporation (2020–2022). A. Repici has received research grants and speakerʼs fees from Boston Scientific (2020–2022), Fujifilm (2019–2022), and Norgine (2020–2022); he is also on an advisory board for Fujifilm (2019–2022). E. Rondonotti has been an Expert group member and speaker for Fujifilm (January–December 2021), and provided consultancy to Medtronic (July 2021–July 2022); his department received a research grant from Fujifilm (January–December 2021). Y. Saitoʼs department is conducting joint research with the NEC Corporation in developing AI for colonoscopy (April 2016–March 2023); he or his department will hold joint patents with the NEC Corporation, and five patents are pending. P. Sharma is providing consultancy services to Bausch, Boston Scientific, CDx Labs, Covidien LP, Exact Sciences, Fujifilm Medical Systems, Lucid, Lumendi, Medtronic, Phathom, Olympus, Takeda, and Samsung Bioepis (ongoing); his department is receiving research support from Cosmo Pharmaceuticals, Covidien, Docbot, ERBE, Fujifilm, Ironwood Pharmaceuticals, Olympus, and Medtronic. C. Spada has provided consultancy to Medtronic (2018–2022) and AnX Robotics (2018–2022). M. Abdelrahim, M. Areia, I. Boskoski, D. Domagk, A. Ebigbo, T. Eelbode, M. Häfner, R. Kuvaev, D. Libânio, M. Palazzo, M. Rutter, P. Sinonquel, M. Spadaccini, and A. Veitch have no competing interests., (European Society of Gastrointestinal Endoscopy. All rights reserved.)
- Published
- 2022
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7. Chronic cholecystitis: Diagnostic and therapeutic insights from formerly bile-farmed Asiatic black bears (Ursus thibetanus).
- Author
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Kalogeropoulu SK, Lloyd EJ, Rauch H, Redtenbacher I, Häfner M, Burgener IA, and Painer-Gigler J
- Subjects
- Animals, Anti-Bacterial Agents therapeutic use, Bile microbiology, Cholecystitis diagnosis, Cholecystitis drug therapy, Cholecystitis veterinary, Gallbladder Diseases veterinary, Ursidae
- Abstract
Across Southeast Asia and China, more than 17000 Asian bears are kept under suboptimal conditions and farmed for their bile to meet the consumer demand for traditional medicine products. Years of unsterile and repetitive bile extraction contribute to the development of chronic sterile or bacterial cholecystitis, a pathology commonly diagnosed in formerly bile-farmed bears. In both human and veterinary medicine, the diagnostic value of the macroscopic bile examination for assessing gallbladder disease is unclear. The objective of this study is to identify the role of gallbladder bile color, viscosity, and turbidity, while comparing them with established markers of cholecystitis. Moreover, it aims to define the optimal duration of oral antibiotic treatment for chronic bacterial cholecystitis in bears associated with bile farming. Thirty-nine adult, formerly bile-farmed Asiatic black bears (Ursus thibetanus) were examined under anesthesia and underwent percutaneous ultrasound guided cholecystocentesis. A total of 59 bile samples were collected with 20 animals sampled twice to evaluate the therapeutic success. All bile aspirates were assessed macroscopically and microscopically followed by submission for bacterial culture and antimicrobial sensitivity. In the majority of bears, samples with cytological evidence of bactibilia lacked inflammatory cells and did not always correlate with positive bacterial cultures. The most common bacterial isolates were Enterococcus spp, Streptococcus spp and Escherichia coli. Based on our findings, the optimal duration of antibiotic treatment for chronic bacterial cholecystitis is 30 days. Moreover, unlike Gamma-glutamyl Transferase (GGT) and gallbladder wall thickness, the organoleptic properties of bile were found to be reliable markers of chronic gallbladder inflammation with color and turbidity indicating cholestasis. The current study highlights the importance of cholecystocentesis for the management of gallbladder disease and provides initial results on the possible diagnostic value of macroscopic bile examination., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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8. Computer-aided detection of colorectal polyps using a newly generated deep convolutional neural network: from development to first clinical experience.
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Pfeifer L, Neufert C, Leppkes M, Waldner MJ, Häfner M, Beyer A, Hoffman A, Siersema PD, Neurath MF, and Rath T
- Subjects
- Artificial Intelligence, Colonoscopy methods, Computers, Humans, Neural Networks, Computer, Adenoma diagnostic imaging, Adenoma pathology, Colonic Polyps diagnostic imaging, Colonic Polyps pathology, Colorectal Neoplasms diagnostic imaging, Colorectal Neoplasms pathology
- Abstract
Aim: The use of artificial intelligence represents an objective approach to increase endoscopist's adenoma detection rate (ADR) and limit interoperator variability. In this study, we evaluated a newly developed deep convolutional neural network (DCNN) for automated detection of colorectal polyps ex vivo as well as in a first in-human trial., Methods: For training of the DCNN, 116 529 colonoscopy images from 278 patients with 788 different polyps were collected. A subset of 10 467 images containing 504 different polyps were manually annotated and treated as the gold standard. An independent set of 45 videos consisting of 15 534 single frames was used for ex vivo performance testing. In vivo real-time detection of colorectal polyps during routine colonoscopy by the DCNN was tested in 42 patients in a back-to-back approach., Results: When analyzing the test set of 15 534 single frames, the DCNN's sensitivity and specificity for polyp detection and localization within the frame was 90% and 80%, respectively, with an area under the curve of 0.92. In vivo, baseline polyp detection rate and ADR were 38% and 26% and significantly increased to 50% (P = 0.023) and 36% (P = 0.044), respectively, with the use of the DCNN. Of the 13 additionally with the DCNN detected lesions, the majority were diminutive and flat, among them three sessile serrated adenomas., Conclusion: This newly developed DCNN enables highly sensitive automated detection of colorectal polyps both ex vivo and during first in-human clinical testing and could potentially increase the detection of colorectal polyps during colonoscopy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2021
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9. Art in Endoscopy: "An icon in a colon".
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Häfner M
- Published
- 2021
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10. Individual 3D-printed fixation masks for radiotherapy: first clinical experiences.
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Mattke M, Rath D, Häfner MF, Unterhinninghofen R, Sterzing F, Debus J, and Giesel FL
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- Humans, Head and Neck Neoplasms radiotherapy, Immobilization methods, Masks, Printing, Three-Dimensional, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Purpose: To show the feasibility of 3D-printed fixation masks for whole brain radiation therapy in a clinical setting and perform a first comparison to an established thermoplastic mask system., Methods: Six patients were irradiated with whole brain radiotherapy using individually 3D-printed masks. Daily image guidance and position correction were performed prior to each irradiation fraction. The vectors of the daily position correction were compared to two collectives of patients, who were irradiated using the standard thermoplastic mask system (one cohort with head masks; one cohort with head and neck masks)., Results: The mean systematic errors in the experimental cohort ranged between 0.59 and 2.10 mm which is in a comparable range to the control groups (0.18 mm-0.68 mm and 0.34 mm-2.96 mm, respectively). The 3D-printed masks seem to be an alternative to the established thermoplastic mask systems. Nevertheless, further investigation will need to be performed., Conclusion: The prevailing study showed a reliable and reproducible interfractional positioning accuracy using individually 3D-printed masks for whole brain irradiation in a clinical routine. Further investigations, especially concerning smaller target volumes or other areas of the body, need to be performed before using the system on a larger basis.
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- 2021
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11. Total Synthesis of the Diterpene Waihoensene.
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Rosenbaum LC, Häfner M, and Gaich T
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A racemic and scalable enantioselective total synthesis of (+)-waihoensene was accomplished. (+)-Waihoensene belongs to the diterpene natural product family, and it features an angular triquinane substructure motif. Its tetracyclic [6.5.5.5]backbone is all-cis-fused, containing six contiguous stereocenters, four of which are quaternary. These structural features were efficiently installed by means of a diastereoselective radical cyclization, followed by an intramolecular Pauson-Khand reaction, a diastereoselective α-alkylation, and a diastereoselective 1,4-addition reaction. Enantioselectivity was introduced at an early stage, by an asymmetric palladium catalyzed decarboxylative allylation reaction on gram scale., (© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
- Published
- 2021
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12. Simultaneous integrated boost concepts in definitive radiation therapy for esophageal cancer: outcomes and toxicity.
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Ristau J, Thiel M, Katayama S, Schlampp I, Lang K, Häfner MF, Herfarth K, Debus J, and Koerber SA
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- Adult, Aged, Aged, 80 and over, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Prognosis, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoradiotherapy mortality, Esophageal Neoplasms therapy, Esophageal Squamous Cell Carcinoma therapy, Neoplasm Recurrence, Local therapy, Radiotherapy, Intensity-Modulated mortality
- Abstract
Background: Radiation therapy and chemoradiation therapy play a major role in the definitive management of esophageal cancer. Survival in esophageal cancer patients is still relatively poor, mostly due to high rates of local recurrence and distant metastases. It is hypothesized that dose escalation in radiotherapy could improve outcomes. Therefore, this retrospective analysis aimed to investigate the outcomes and toxicity in patients treated with local dose escalation by means of using simultaneous integrated boost concepts., Methods: Between 2012 and 2018, 101 patients with esophageal carcinoma were analyzed in this monocentric, retrospective study. All patients received definitive chemoradiation or radiation therapy alone as intensity modulated radiotherapy. The prescribed dose was 50.4 Gy in 28 fractions to the primary tumor and the elective lymph nodes as well as a simultaneous integrated boost (SIB) with 58.8 Gy to macroscopic tumor and lymph node metastases. Endpoints were overall survival (OS), progression free survival (PFS), local control rate (LCR) and toxicity., Results: 60 patients (59.4%) received chemoradiation, 41 patients (40.6%) radiotherapy alone. The median follow up was 17 months (range 0-75 months). OS, PFS and LCR were at 63.9%, 53.9% and 59.9% after 1 year and 37.6%, 34.5% and 36.1%, respectively after 3 years. 16 patients (15.8%) in total developed a locoregional recurrence within the field of radiation. In 48 patients (47.5%) at least one grade III° (CTCAE) toxicity was documented during radiotherapy, mostly dysphagia (36 pat., 75%). One patient suffered from a grade IV° pneumonia., Conclusion: This retrospective analysis demonstrates that a SIB concept in definitive (chemo)radiation therapy is safe and feasible, showing acceptable outcomes in this patient cohort. Considering that this cohort mainly consists of elderly patients not eligible for chemotherapy in many cases, we emphasize the aspect of SIB radiation therapy as potential partial compensation for omitted simultaneous chemotherapy. Prospective studies are needed for validation.
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- 2021
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13. Improving CNN training on endoscopic image data by extracting additionally training data from endoscopic videos.
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Wimmer G, Häfner M, and Uhl A
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- Diagnosis, Computer-Assisted, Humans, Image Processing, Computer-Assisted, Colonic Polyps diagnostic imaging, Neural Networks, Computer
- Abstract
In this work we present a technique to deal with one of the biggest problems for the application of convolutional neural networks (CNNs) in the area of computer assisted endoscopic image diagnosis, the insufficient amount of training data. Based on patches from endoscopic images of colonic polyps with given label information, our proposed technique acquires additional (labeled) training data by tracking the area shown in the patches through the corresponding endoscopic videos and by extracting additional image patches from frames of these areas. So similar to the widely used augmentation strategies, additional training data is produced by adding images with different orientations, scales and points of view than the original images. However, contrary to augmentation techniques, we do not artificially produce image data but use real image data from videos under different image recording conditions (different viewpoints and image qualities). By means of our proposed method and by filtering out all extracted images with insufficient image quality, we are able to increase the amount of labeled image data by factor 39. We will show that our proposed method clearly and continuously improves the performance of CNNs., (Copyright © 2020. Published by Elsevier Ltd.)
- Published
- 2020
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14. Intrafractional vaginal dilation in anal cancer patients undergoing pelvic radiotherapy (DILANA) - a prospective, randomized, 2-armed phase-II-trial.
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Arians N, Häfner M, Krisam J, Lang K, Wark A, Koerber SA, Hommertgen A, and Debus J
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- Adolescent, Adult, Aged, Aged, 80 and over, Anus Neoplasms pathology, Female, Humans, Middle Aged, Pelvic Neoplasms pathology, Prognosis, Prospective Studies, Quality of Life, Radiation Injuries etiology, Radiotherapy Dosage, Vaginal Diseases etiology, Young Adult, Anus Neoplasms therapy, Chemoradiotherapy adverse effects, Pelvic Neoplasms therapy, Radiation Injuries pathology, Radiotherapy, Intensity-Modulated adverse effects, Vaginal Diseases pathology
- Abstract
Background: The incidence of anal cancer is rising in the last decades and more women are affected than men. The prognosis after chemoradiation is very good with complete remission rates of 80-90%. Thus, reducing therapy-related toxicities and improving quality of life are of high importance. With the development of new radiotherapy techniques like IMRT (Intensity-modulated radiotherapy), the incidence of acute and chronic gastrointestinal toxicities has already been reduced. However, especially in female anal cancer patients genital toxicities like vaginal fibrosis and stenosis are of great relevance, too. Up to now, there are no prospective data reporting incidence rates, techniques of prevention or impact on quality of life. The aim of the DILANA trial is to evaluate the incidence and grade of vaginal fibrosis, to optimize radiotherapy by reducing dose to the vaginal wall to minimize genital toxicities and improve quality of life of anal cancer patients., Methods: The study is designed as a prospective, randomized, two-armed, open, single-center phase-II-trial. Sixty patients will be randomized into one of two arms, which differ only in the diameter of a tampon used during treatment. All patients will receive standard (chemo) radiation with a total dose of 45-50.4 Gy to the pelvic and inguinal nodes with a boost to the anal canal up to 54-60 Gy. The primary objective is the assessment of the incidence and grade of vaginal fibrosis 12 months after (chemo) radiation depending on the extent of vaginal dilation. Secondary endpoints are toxicities according to the CTC AE version 5.0 criteria, assessment of clinical feasibility of daily use of a tampon, assessment of compliance for the use of a vaginal dilator and quality of life., Discussion: Prospective studies are needed evaluating the incidence and grade of vaginal fibrosis after (chemo) radiation in female anal cancer patients. Furthermore, the assessment of techniques to reduce the incidence of vaginal fibrosis like intrafractional vaginal dilation as well as other radiotherapy-independent methods like using a vaginal dilator are essential. Additionally, implementation of a systematic assessment of vaginal stenosis is necessary to grant reproducibility and comparability of future data., Trial Registration: The trial is registered with clinicaltrials.gov (NCT04094454, 19.09.2019).
- Published
- 2020
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15. Percutaneous Endoscopic Gastrostomy Tube Placement in Patients with Head and Neck Cancer Treated with Radiotherapy.
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Lang K, ElShafie RA, Akbaba S, Koschny R, Bougatf N, Bernhardt D, Welte SE, Adeberg S, Häfner M, Kargus S, Plinkert PK, Debus J, and Rieken S
- Abstract
Background and Aim: The primary aim of our study was to evaluate percutaneous endoscopic gastrostomy (PEG) tube placement depending on body weight and body mass index in patients undergoing radiotherapy (RT) for head and neck cancer (HNC). A secondary aim was to evaluate the course of weight change following PEG placement., Methods: We retrospectively reviewed the medical records of 186 patients with HNC undergoing radiotherapy (RT) or chemoradiotherapy (CRT) at our institution between January 2010 and August 2017. Initial weight and nutritional intake were analyzed prior to RT initiation and then followed throughout treatment until completion. Based on these data, the indication of PEG placement was determined. Medical records were also reviewed to analyze PEG-related acute toxicities., Results: A total of 186 patients met inclusion criteria. Patients were most commonly male (n=123, 66.1%) with squamous cell carcinoma (n=164, 88.2%). Patients who had dysphagia prior to treatment initiation as well as patients with a BMI <18.5 kg/m
2 needed PEG placement earlier during the treatment course. Low-grade toxicities related to PEG insertion were observed in 10.7% patients, with peristomal pain and redness adjacent to the PEG tube insertion site being most common. High-grade toxicities, such as peritonitis and organ injury, were found in 4.9% of patients., Conclusion: Underweight patients and those with preexisting dysphagia should be closely screened during RT for weight loss and decreased oral intake. For weight loss greater than 4.5% during the treatment of HNC, early PEG-tube placement should be considered. Further prospective studies are needed to confirm these findings, and delineate a scoring system for timing of PEG use (prophylactic vs reactive) as well as assess the quality of life in patients with HNC who receive PEG placement., Competing Interests: Dr Sebastian Adeberg report personal fees from Merck Serono GmbH, other from Novocure, personal fees from Accuray International Sarl, outside the submitted work. Prof. Dr. Jürgen Debus report grants from Merck Serono, grants from Accuray, grants, non-financial support from Siemens Healthineers, non-financial support from Research Labs, outside the submitted work. The authors report no other conflict of interest in this work., (© 2020 Lang et al.)- Published
- 2020
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16. Enantioselective Synthesis of Cyclohepta[ b ]indoles via Pd-Catalyzed Cyclopropane C(sp 3 )-H Activation as a Key Step.
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Häfner M, Sokolenko YM, Gamerdinger P, Stempel E, and Gaich T
- Abstract
An enantioselective synthesis of functionalized cyclohepta[ b ]indoles via Pd-catalyzed cyclopropane C-H activation followed by olefination and indole-vinylcyclopropane rearrangement is reported. The design of the chiral cyclopropane precursor was such that both enantiomeric cyclohepta[ b ]indoles were accessed from a single compound exhibiting a "hidden" symmetry plane. The scope of the method was demonstrated by varying the substituents on the cyclopropane as well as on the heterocycle itself.
- Published
- 2019
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17. Differential response of esophageal cancer cells to particle irradiation.
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Hartfiel S, Häfner M, Perez RL, Rühle A, Trinh T, Debus J, Huber PE, and Nicolay NH
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- Adenocarcinoma radiotherapy, Carcinoma, Squamous Cell radiotherapy, DNA Repair radiation effects, Esophageal Neoplasms radiotherapy, Humans, Tumor Cells, Cultured, Adenocarcinoma pathology, Apoptosis radiation effects, Carcinoma, Squamous Cell pathology, DNA Breaks, Double-Stranded radiation effects, Esophageal Neoplasms pathology, Photons
- Abstract
Background: Radiation therapy is a mainstay in the treatment of esophageal cancer (EC) patients, and photon radiotherapy has proved beneficial both in the neoadjuvant and the definitive setting. However, regarding the still poor prognosis of many EC patients, particle radiation employing a higher biological effectiveness may help to further improve patient outcomes. However, the influence of clinically available particle radiation on EC cells remains largely unknown., Methods: Patient-derived esophageal adenocarcinoma and squamous cell cancer lines were treated with photon and particle irradiation using clinically available proton (
1 H), carbon (12 C) or oxygen (16 O) beams at the Heidelberg Ion Therapy Center. Histology-dependent clonogenic survival was calculated for increasing physical radiation doses, and resulting relative biological effectiveness (RBE) was calculated for each radiation modality. Cell cycle effects caused by photon and particle radiation were assessed, and radiation-induced apoptosis was measured in adenocarcinoma and squamous cell EC samples by activated caspase-3 and sub-G1 populations. Repair kinetics of DNA double strand breaks induced by photon and particle radiation were investigated., Results: While both adenocarcinoma EC cell lines demonstrated increasing sensitivities for1 H,12 C and16 O radiation, the two squamous cell carcinoma lines exhibited a more heterogeneous response to photon and particle treatment; average RBE values were calculated as 1.15 for1 H, 2.3 for12 C and 2.5 for16 O irradiation. After particle irradiation, squamous cell EC samples reacted with an increased and prolonged block in G2 phase of the cell cycle compared to adenocarcinoma cells. Particle radiation resulted in an incomplete repair of radiation-induced DNA double strand breaks in both adenocarcinoma and squamous cell carcinoma samples, with the levels of initial strand break induction correlating well with the individual cellular survival after photon and particle radiation. Similarly, EC samples demonstrated heterogeneous levels of radiation-induced apoptosis that also corresponded to the observed cellular survival of individual cell lines., Conclusions: Esophageal cancer cells exhibit differential responses to irradiation with photons and1 H,12 C and16 O particles that were independent of tumor histology. Therefore, yet unknown molecular markers beyond histology may help to establish which esophageal cancer patients benefit from the biological effects of particle treatment.- Published
- 2019
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18. Bimodal Radiotherapy with Active Raster-Scanning Carbon Ion Radiotherapy and Intensity-Modulated Radiotherapy in High-Risk Nasopharyngeal Carcinoma Results in Excellent Local Control.
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Akbaba S, Held T, Lang K, Forster T, Federspil P, Herfarth K, Häfner M, Plinkert P, Rieken S, Debus J, and Adeberg S
- Abstract
Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable ( n = 17, 65%) or incompletely resected ( n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy ( n = 21). Results: The median follow-up time was 40 months (range 10⁻97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% ( n = 15/25), partial tumor remission (PR) in 20% ( n = 5/25), and stable disease (SD) in 12% ( n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active raster-scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
- Published
- 2019
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19. Quest for the best endoscopic imaging modality for computer-assisted colonic polyp staging.
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Wimmer G, Gadermayr M, Wolkersdörfer G, Kwitt R, Tamaki T, Tischendorf J, Häfner M, Yoshida S, Tanaka S, Merhof D, and Uhl A
- Subjects
- Colonic Polyps pathology, Coloring Agents administration & dosage, Humans, Image Enhancement methods, Narrow Band Imaging methods, Precancerous Conditions pathology, Video Recording methods, Colonic Polyps diagnostic imaging, Colonoscopy methods, Colorectal Neoplasms prevention & control, Diagnosis, Computer-Assisted methods, Precancerous Conditions diagnostic imaging
- Abstract
Background: It was shown in previous studies that high definition endoscopy, high magnification endoscopy and image enhancement technologies, such as chromoendoscopy and digital chromoendoscopy [narrow-band imaging (NBI), i-Scan] facilitate the detection and classification of colonic polyps during endoscopic sessions. However, there are no comprehensive studies so far that analyze which endoscopic imaging modalities facilitate the automated classification of colonic polyps. In this work, we investigate the impact of endoscopic imaging modalities on the results of computer-assisted diagnosis systems for colonic polyp staging., Aim: To assess which endoscopic imaging modalities are best suited for the computer-assisted staging of colonic polyps., Methods: In our experiments, we apply twelve state-of-the-art feature extraction methods for the classification of colonic polyps to five endoscopic image databases of colonic lesions. For this purpose, we employ a specifically designed experimental setup to avoid biases in the outcomes caused by differing numbers of images per image database. The image databases were obtained using different imaging modalities. Two databases were obtained by high-definition endoscopy in combination with i-Scan technology (one with chromoendoscopy and one without chromoendoscopy). Three databases were obtained by high-magnification endoscopy (two databases using narrow band imaging and one using chromoendoscopy). The lesions are categorized into non-neoplastic and neoplastic according to the histological diagnosis., Results: Generally, it is feature-dependent which imaging modalities achieve high results and which do not. For the high-definition image databases, we achieved overall classification rates of up to 79.2% with chromoendoscopy and 88.9% without chromoendoscopy. In the case of the database obtained by high-magnification chromoendoscopy, the classification rates were up to 81.4%. For the combination of high-magnification endoscopy with NBI, results of up to 97.4% for one database and up to 84% for the other were achieved. Non-neoplastic lesions were classified more accurately in general than non-neoplastic lesions. It was shown that the image recording conditions highly affect the performance of automated diagnosis systems and partly contribute to a stronger effect on the staging results than the used imaging modality., Conclusion: Chromoendoscopy has a negative impact on the results of the methods. NBI is better suited than chromoendoscopy. High-definition and high-magnification endoscopy are equally suited., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest.
- Published
- 2019
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20. Training of polyp staging systems using mixed imaging modalities.
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Wimmer G, Gadermayr M, Kwitt R, Häfner M, Tamaki T, Yoshida S, Tanaka S, Merhof D, and Uhl A
- Subjects
- Algorithms, Colonoscopy, Colorectal Neoplasms diagnostic imaging, Diagnostic Imaging methods, Endoscopy, Humans, Image Enhancement methods, Colonic Polyps diagnostic imaging, Diagnosis, Computer-Assisted methods, Pattern Recognition, Automated
- Abstract
Background: In medical image data sets, the number of images is usually quite small. The small number of training samples does not allow to properly train classifiers which leads to massive overfitting to the training data. In this work, we investigate whether increasing the number of training samples by merging datasets from different imaging modalities can be effectively applied to improve predictive performance. Further, we investigate if the extracted features from the employed image representations differ between different imaging modalities and if domain adaption helps to overcome these differences., Method: We employ twelve feature extraction methods to differentiate between non-neoplastic and neoplastic lesions. Experiments are performed using four different classifier training strategies, each with a different combination of training data. The specifically designed setup for these experiments enables a fair comparison between the four training strategies., Results: Combining high definition with high magnification training data and chromoscopic with non-chromoscopic training data partly improved the results. The usage of domain adaptation has only a small effect on the results compared to just using non-adapted training data., Conclusion: Merging datasets from different imaging modalities turned out to be partially beneficial for the case of combining high definition endoscopic data with high magnification endoscopic data and for combining chromoscopic with non-chromoscopic data. NBI and chromoendoscopy on the other hand are mostly too different with respect to the extracted features to combine images of these two modalities for classifier training., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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21. Fisher encoding of convolutional neural network features for endoscopic image classification.
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Wimmer G, Vécsei A, Häfner M, and Uhl A
- Abstract
We propose an approach for the automated diagnosis of celiac disease (CD) and colonic polyps (CP) based on applying Fisher encoding to the activations of convolutional layers. In our experiments, three different convolutional neural network (CNN) architectures (AlexNet, VGG-f, and VGG-16) are applied to three endoscopic image databases (one CD database and two CP databases). For each network architecture, we perform experiments using a version of the net that is pretrained on the ImageNet database, as well as a version of the net that is trained on a specific endoscopic image database. The Fisher representations of convolutional layer activations are classified using support vector machines. Additionally, experiments are performed by concatenating the Fisher representations of several layers to combine the information of these layers. We will show that our proposed CNN-Fisher approach clearly outperforms other CNN- and non-CNN-based approaches and that our approach requires no training on the target dataset, which results in substantial time savings compared with other CNN-based approaches.
- Published
- 2018
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22. Active pump-seed-pulse synchronization for OPCPA with sub-2-fs residual timing jitter: erratum.
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Prinz S, Häfner M, Schultze M, Teisset CY, Bessing R, Michel K, Kienberger R, and Metzger T
- Abstract
In the original manuscript, a residual RMS timing jitter below 2 fs between pump and seed pulses in the stabilized case was claimed. Following a reevaluation of the data, this was underestimated. Due to a rounding error in the calibration routine, a miscalculated calibration factor was extracted. By using a higher precision, the updated residual timing jitter amounts to 2.76 fs, or sub-3 fs. In this erratum, the calibration routine is briefly reviewed and Fig. 4, which presents the timing jitter in the stabilized and unstabilized case, is updated. All other results remain unaffected.
- Published
- 2018
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23. Thin-disk pumped optical parametric chirped pulse amplifier delivering CEP-stable multi-mJ few-cycle pulses at 6 kHz.
- Author
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Prinz S, Schnitzenbaumer M, Potamianos D, Schultze M, Stark S, Häfner M, Teisset CY, Wandt C, Michel K, Kienberger R, Bernhardt B, and Metzger T
- Abstract
We present an optical parametric chirped pulse amplifier (OPCPA) delivering CEP-stable ultrashort pulses with 7 fs, high energies of more than 1.8 mJ and high average output power exceeding 10 W at a repetition rate of 6 kHz. The system is pumped by a picosecond regenerative thin-disk amplifier and exhibits an excellent long-term stability. In a proof-of-principle experiment, high harmonic generation is demonstrated in neon up to the 61
st order.- Published
- 2018
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24. Alcohol representations are socially situated: An investigation of beverage representations by using a property generation task.
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Keesman M, Aarts H, Ostafin BD, Verwei S, Häfner M, and Papies EK
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- Adult, Alcohol Drinking prevention & control, Drinking Behavior, Female, Health Behavior, Humans, Male, Young Adult, Alcoholic Beverages, Beverages, Social Environment
- Abstract
Previous research suggests that people's representations of alcoholic beverages play an important role in drinking behavior. However, relatively little is known about the contents of these representations. Here, we introduce the property generation task as a tool to explore these representations in detail. In a laboratory study (N = 110), and a bar field-study (N = 56), participants listed typical properties of alcoholic beverages, sugary beverages, and water. Each of these properties was then categorized using a previously developed, hierarchical coding scheme. For example, the property "sweet" was categorized as referring to "taste", which falls under "sensory experience", which falls under "consumption situation". Afterwards, participants completed measures of drinking behavior and alcohol craving. Results showed that alcoholic beverages were strongly represented in terms of consumption situations, with 57% and 69% of properties relating to consumption in the laboratory and the bar study, respectively. Specifically, alcoholic beverages were more strongly represented in terms of the social context of consumption (e.g., "with friends") than the other beverages. In addition, alcoholic beverages were strongly represented in terms of sensory experiences (e.g. "sweet") and positive outcomes (e.g. "creates fun"), as were the sugary beverages and water. In Study 1, the extent to which alcoholic beverages were represented in terms of social context was positively associated with craving and regularly consuming alcohol. The property generation task provides a useful tool to access people's idiosyncratic representations of alcoholic beverages. This may further our understanding of drinking behavior, and help to tailor research and interventions to reduce drinking of alcoholic and other high-calorie beverages., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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25. Interobserver variability in target volume delineation of hepatocellular carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the German Society for Radiation Oncology (DEGRO).
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Gkika E, Tanadini-Lang S, Kirste S, Holzner PA, Neeff HP, Rischke HC, Reese T, Lohaus F, Duma MN, Dieckmann K, Semrau R, Stockinger M, Imhoff D, Kremers N, Häfner MF, Andratschke N, Nestle U, Grosu AL, Guckenberger M, and Brunner TB
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Observer Variation, Reproducibility of Results, Sensitivity and Specificity, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology, Tomography, X-Ray Computed methods, Tumor Burden
- Abstract
Background: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel., Methods: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch., Results: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT., Conclusion: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.
- Published
- 2017
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26. Craniospinal irradiation using helical tomotherapy for central nervous system tumors.
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Schiopu SR, Habl G, Häfner M, Katayama S, Herfarth K, Debus J, and Sterzing F
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Disease-Free Survival, Dose-Response Relationship, Radiation, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Organs at Risk radiation effects, Retrospective Studies, Young Adult, Central Nervous System Neoplasms radiotherapy, Craniospinal Irradiation adverse effects, Radiotherapy, Intensity-Modulated adverse effects
- Abstract
The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1-4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1-4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume., (© The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)
- Published
- 2017
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27. Anger and aggression problems in veterans are associated with an increased acoustic startle reflex.
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Heesink L, Kleber R, Häfner M, van Bedaf L, Eekhout I, and Geuze E
- Subjects
- Acoustic Stimulation, Adult, Humans, Male, Aggression physiology, Anger physiology, Anxiety physiopathology, Reflex, Startle physiology, Veterans
- Abstract
Anger and aggression are frequent problems in deployed military personnel. A lowered threshold of perceiving and responding to threat can trigger impulsive aggression. This can be indicated by an exaggerated startle response. Fifty-two veterans with anger and aggression problems (Anger group) and 50 control veterans were tested using a startle experiment with 10 startle probes and 10 prepulse trials, presented in a random order and with a random interval between the trials. Predictors (demographics, Trait Anger, State Anger, Harm Avoidance and Anxious Arousal) for the startle response within the Anger group were tested. Increased EMG responses were found to the startle probes in the Anger Group compared to the Control group, but not to the prepulse trials. Furthermore, Harm Avoidance and State Anger predicted the increased startle reflex within the Anger group, whereas Trait Anger was negatively related to the startle reflex. These findings indicate that threat reactivity is increased in anger and aggression problems. These problems are not only caused by an anxious predisposition, the degree of anger also predicts the startle reflex., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2017
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28. Mindfulness Reduces Reactivity to Food Cues: Underlying Mechanisms and Applications in Daily Life.
- Author
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Keesman M, Aarts H, Häfner M, and Papies EK
- Abstract
Purpose of Review: Mindfulness-based interventions are becoming increasingly popular as a means to facilitate healthy eating. We suggest that the decentering component of mindfulness, which is the metacognitive insight that all experiences are impermanent, plays an especially important role in such interventions. To facilitate the application of decentering, we address its psychological mechanism to reduce reactivity to food cues, proposing that it makes thoughts and simulations in response to food cues less compelling. We discuss supporting evidence, applications, and challenges for future research., Recent Findings: Experimental and correlational studies consistently find that the adoption of a decentering perspective reduces subjective cravings, physiological reactivity such as salivation, and unhealthy eating., Summary: We suggest that the decentering perspective can be adopted in any situation to reduce reactivity to food cues. Considering people's high exposure to food temptations in daily life, this makes it a powerful tool to empower people to eat healthily.
- Published
- 2017
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29. Consumption Simulations Induce Salivation to Food Cues.
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Keesman M, Aarts H, Vermeent S, Häfner M, and Papies EK
- Subjects
- Cognition, Female, Humans, Imagination physiology, Male, Young Adult, Cues, Eating psychology, Food, Salivation physiology
- Abstract
Salivation to food cues is typically explained in terms of mere stimulus-response links. However, food cues seem to especially increase salivation when food is attractive, suggesting a more complex psychological process. Adopting a grounded cognition perspective, we suggest that perceiving a food triggers simulations of consuming it, especially when attractive. These simulations then induce salivation, which effectively prepares the body for eating the food. In two experiments, we systematically examined the role of simulations on salivation to food cues. As stimuli, both experiments used an attractive, a neutral, and a sour food, as well as a non-food control object. In Experiment 1, participants were instructed to simulate eating every object they would be exposed to. We then exposed them to each object separately. Salivation was assessed by having participants spit their saliva into a cup after one minute of exposure. In Experiment 2, we instructed half of participants to simulate eating each object, and half to merely look at them, while measuring salivation as in Experiment 1. Afterwards, participants rated their simulations and desire to eat for each object separately. As predicted, foods increased salivation compared to the non-food control object, especially when they were attractive or sour (Exp. 1 and 2). Importantly, attractive and sour foods especially increased salivation when instructed to simulate (Exp. 2). These findings suggest that consumption simulations play an important role in inducing salivary responses to food cues. We discuss directions for future research as well as the role of simulations for other appetitive processes., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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30. Synthesis of Highly Selective Submicromolar Microcystin-Based Inhibitors of Protein Phosphatase (PP)2A over PP1.
- Author
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Fontanillo M, Zemskov I, Häfner M, Uhrig U, Salvi F, Simon B, Wittmann V, and Köhn M
- Abstract
Research and therapeutic targeting of the phosphoserine/threonine phosphatases PP1 and PP2A is hindered by the lack of selective inhibitors. The microcystin (MC) natural toxins target both phosphatases with equal potency, and their complex synthesis has complicated structure-activity relationship studies in the past. We report herein the synthesis and biochemical evaluation of 11 MC analogues, which was accomplished through an efficient strategy combining solid- and solution-phase approaches. Our approach led to the first MC analogue with submicromolar inhibitory potency that is strongly selective for PP2A over PP1 and does not require the complex lipophilic Adda group. Through mutational and structural analyses, we identified a new key element for binding, as well as reasons for the selectivity. This work gives unprecedented insight into how selectivity between these phosphatases can be achieved with MC analogues., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
- Published
- 2016
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31. A pilot study of confocal laser endomicroscopy for diagnosing gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma.
- Author
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Dolak W, Kiesewetter B, Müllauer L, Mayerhoefer M, Troch M, Trauner M, Häfner M, Raderer M, and Püspök A
- Subjects
- Adult, Aged, Aged, 80 and over, Biopsy, Double-Blind Method, Duodenal Neoplasms diagnostic imaging, Duodenal Neoplasms pathology, Endoscopy, Endosonography, Female, Humans, Lymphoma, B-Cell, Marginal Zone diagnostic imaging, Lymphoma, B-Cell, Marginal Zone pathology, Male, Microscopy, Confocal, Middle Aged, Neoplasm Staging, Pilot Projects, Prospective Studies, Sensitivity and Specificity, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms pathology, Duodenal Neoplasms diagnosis, Lymphoma, B-Cell, Marginal Zone diagnosis, Stomach Neoplasms diagnosis
- Abstract
Background: Patients with gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma require lifelong endoscopic follow-up. This study aimed to establish and evaluate confocal laser endomicroscopy (CLE) criteria for gastrointestinal MALT lymphoma., Methods: This prospective trial was conducted after IRB approval at the Medical University of Vienna. Twenty-four consecutive patients (14 males and 10 females, median age 65 years) referred for staging or follow-up of (former) gastrointestinal MALT lymphoma underwent endosonography (EUS) and CLE including white light endoscopy (WLE) and conventional biopsy sampling of the upper gastrointestinal tract. CLE criteria of the disease were based on the first five patients with histologically proven MALT lymphoma. All CLE datasets were reviewed separately by two CLE experts. The diagnostic modalities were compared using conventional histology as the gold standard., Results: Sixty-two percentages had a positive diagnosis of MALT lymphoma based on histology. The sensitivity was 80 % for EUS (0.51-0.95), 100 % for WLE (0.75-1) and 93 % for CLE (0.66-1); the specificity was 67 % for EUS (0.31-0.91), 23 % for WLE (0.04-0.60) and 100 % for CLE (0.63-1). The agreement with histology was moderate for EUS (kappa 0.47, p = 0.02), fair for WLE (kappa 0.26, p = 0.06) and almost perfect for CLE (kappa 0.91, p < 0.01). Expert evaluation identified all but one case of MALT lymphoma with excellent interobserver agreement (kappa 0.89, p < 0.01). In the case missed by CLE, MALT lymphoma involvement was restricted to deep tissue structures., Conclusions: Despite minor technical limitations, CLE is a promising alternative to conventional biopsy sampling in patients with gastrointestinal MALT lymphoma. CLINICALTRIALS., Gov Number: NCT01583699.
- Published
- 2016
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32. Directional wavelet based features for colonic polyp classification.
- Author
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Wimmer G, Tamaki T, Tischendorf JJ, Häfner M, Yoshida S, Tanaka S, and Uhl A
- Subjects
- Colonic Polyps classification, Humans, Image Enhancement, Machine Learning, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Colonic Polyps diagnostic imaging, Colonoscopy methods, Image Interpretation, Computer-Assisted, Pattern Recognition, Automated methods, Wavelet Analysis
- Abstract
In this work, various wavelet based methods like the discrete wavelet transform, the dual-tree complex wavelet transform, the Gabor wavelet transform, curvelets, contourlets and shearlets are applied for the automated classification of colonic polyps. The methods are tested on 8 HD-endoscopic image databases, where each database is acquired using different imaging modalities (Pentax's i-Scan technology combined with or without staining the mucosa), 2 NBI high-magnification databases and one database with chromoscopy high-magnification images. To evaluate the suitability of the wavelet based methods with respect to the classification of colonic polyps, the classification performances of 3 wavelet transforms and the more recent curvelets, contourlets and shearlets are compared using a common framework. Wavelet transforms were already often and successfully applied to the classification of colonic polyps, whereas curvelets, contourlets and shearlets have not been used for this purpose so far. We apply different feature extraction techniques to extract the information of the subbands of the wavelet based methods. Most of the in total 25 approaches were already published in different texture classification contexts. Thus, the aim is also to assess and compare their classification performance using a common framework. Three of the 25 approaches are novel. These three approaches extract Weibull features from the subbands of curvelets, contourlets and shearlets. Additionally, 5 state-of-the-art non wavelet based methods are applied to our databases so that we can compare their results with those of the wavelet based methods. It turned out that extracting Weibull distribution parameters from the subband coefficients generally leads to high classification results, especially for the dual-tree complex wavelet transform, the Gabor wavelet transform and the Shearlet transform. These three wavelet based transforms in combination with Weibull features even outperform the state-of-the-art methods on most of the databases. We will also show that the Weibull distribution is better suited to model the subband coefficient distribution than other commonly used probability distributions like the Gaussian distribution and the generalized Gaussian distribution. So this work gives a reasonable summary of wavelet based methods for colonic polyp classification and the huge amount of endoscopic polyp databases used for our experiments assures a high significance of the achieved results., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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33. Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.
- Author
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Birk M, Bauerfeind P, Deprez PH, Häfner M, Hartmann D, Hassan C, Hucl T, Lesur G, Aabakken L, and Meining A
- Subjects
- Adult, Europe, Gastroenterology methods, Gastroenterology standards, Humans, Societies, Medical, Upper Gastrointestinal Tract diagnostic imaging, Upper Gastrointestinal Tract pathology, Upper Gastrointestinal Tract surgery, Endoscopy, Gastrointestinal methods, Foreign Bodies diagnosis, Foreign Bodies surgery
- Abstract
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults. Recommendations Nonendoscopic measures 1 ESGE recommends diagnostic evaluation based on the patient's history and symptoms. ESGE recommends a physical examination focused on the patient's general condition and to assess signs of any complications (strong recommendation, low quality evidence). 2 ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence). 3 ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence). 4 ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence). 5 ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence). 6 ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing ("body packing"). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence). Endoscopic measures 7 ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence). 8 ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence). The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence). 9 In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence). 10 ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence). 11 ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence). 12 ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence). 13 After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence)., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2016
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34. Exploring Deep Learning and Transfer Learning for Colonic Polyp Classification.
- Author
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Ribeiro E, Uhl A, Wimmer G, and Häfner M
- Subjects
- Algorithms, Colonic Polyps classification, Humans, Image Processing, Computer-Assisted, Neural Networks, Computer, Pattern Recognition, Automated, Reproducibility of Results, Software, Video Recording, Colonic Polyps diagnostic imaging, Colonoscopy, Diagnosis, Computer-Assisted methods, Endoscopy, Machine Learning
- Abstract
Recently, Deep Learning, especially through Convolutional Neural Networks (CNNs) has been widely used to enable the extraction of highly representative features. This is done among the network layers by filtering, selecting, and using these features in the last fully connected layers for pattern classification. However, CNN training for automated endoscopic image classification still provides a challenge due to the lack of large and publicly available annotated databases. In this work we explore Deep Learning for the automated classification of colonic polyps using different configurations for training CNNs from scratch (or full training) and distinct architectures of pretrained CNNs tested on 8-HD-endoscopic image databases acquired using different modalities. We compare our results with some commonly used features for colonic polyp classification and the good results suggest that features learned by CNNs trained from scratch and the "off-the-shelf" CNNs features can be highly relevant for automated classification of colonic polyps. Moreover, we also show that the combination of classical features and "off-the-shelf" CNNs features can be a good approach to further improve the results.
- Published
- 2016
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35. Local fractal dimension based approaches for colonic polyp classification.
- Author
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Häfner M, Tamaki T, Tanaka S, Uhl A, Wimmer G, and Yoshida S
- Subjects
- Algorithms, Humans, Image Enhancement methods, Machine Learning, Reproducibility of Results, Sensitivity and Specificity, Colonic Polyps pathology, Colonoscopy methods, Fractals, Image Interpretation, Computer-Assisted methods, Pattern Recognition, Automated methods
- Abstract
This work introduces texture analysis methods that are based on computing the local fractal dimension (LFD; or also called the local density function) and applies them for colonic polyp classification. The methods are tested on 8 HD-endoscopic image databases, where each database is acquired using different imaging modalities (Pentax's i-Scan technology combined with or without staining the mucosa) and on a zoom-endoscopic image database using narrow band imaging. In this paper, we present three novel extensions to a LFD based approach. These extensions additionally extract shape and/or gradient information of the image to enhance the discriminativity of the original approach. To compare the results of the LFD based approaches with the results of other approaches, five state of the art approaches for colonic polyp classification are applied to the employed databases. Experiments show that LFD based approaches are well suited for colonic polyp classification, especially the three proposed extensions. The three proposed extensions are the best performing methods or at least among the best performing methods for each of the employed databases. The methods are additionally tested by means of a public texture image database, the UIUCtex database. With this database, the viewpoint invariance of the methods is assessed, an important features for the employed endoscopic image databases. Results imply that most of the LFD based methods are more viewpoint invariant than the other methods. However, the shape, size and orientation adapted LFD approaches (which are especially designed to enhance the viewpoint invariance) are in general not more viewpoint invariant than the other LFD based approaches., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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- View/download PDF
36. Intraductal biliopancreatic imaging: European Society of Gastrointestinal Endoscopy (ESGE) technology review.
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Tringali A, Lemmers A, Meves V, Terheggen G, Pohl J, Manfredi G, Häfner M, Costamagna G, Devière J, Neuhaus H, Caillol F, Giovannini M, Hassan C, and Dumonceau JM
- Subjects
- Bile Ducts, Europe, Humans, Bile Duct Diseases diagnosis, Endoscopy, Gastrointestinal methods, Gastroenterology, Pancreatic Diseases diagnosis, Societies, Medical
- Abstract
This technology review expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) on the available techniques for intraductal biliopancreatic imaging. The three cholangioscopy techniques are described: the "dual-operator" and " single-operator" mother-baby approaches using dedicated instruments, and the "direct" technique using currently available ultrathin gastroscopes. The mother-baby method is standardized and reproducible, while direct cholangioscopy is technically demanding and its safety requires further evaluation. As well as direct visualization of the bile ducts, cholangioscopy has the further advantage of allowing targeted biopsy. Image quality is still suboptimal for single-operator cholangioscopy, while the other techniques have achieved adequately detailed imaging. The costs of mother-baby cholangioscopy are high and its application in clinical practice should be restricted to selected cases (i.e. indeterminate biliary strictures/intraluminal lesions, difficult biliary stones) and to the setting of tertiary care centers. Peroral pancreatoscopy may find an indication in situations where other imaging modalities (mainly EUS) are inconclusive (i.e. delineation of main duct intraductal papillary mucinous neoplasia extension, sampling of indeterminate main pancreatic duct strictures). Intraductal ultrasonography (IDUS) has a poorer performance than EUS in the staging of pancreatic malignancies and can increase the risk of pancreatitis. A promising indication for IDUS could be the evaluation of indeterminate biliary strictures and ampullary tumors. Probe-based confocal laser endomicroscopy (pCLE) of the bile ducts is a difficult and expensive technique. Appropriate training needs to be established, since interpretation of images is challenging. pCLE can be an important diagnostic tool in the setting of indeterminate biliary strictures., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2015
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- View/download PDF
37. A pilot study of the endomicroscopic assessment of tumor extension in Barrett's esophagus-associated neoplasia before endoscopic resection.
- Author
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Dolak W, Mesteri I, Asari R, Preusser M, Tribl B, Wrba F, Schoppmann SF, Hejna M, Trauner M, Häfner M, and Püspök A
- Abstract
Background and Study Aims: Barrett's esophagus (BE) - associated neoplasia can be treated endoscopically, but accurate assessment before intervention is challenging. This study aimed to investigate the role of confocal laser endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral tumor and subsquamous tumor (SST) extension., Patients and Methods: In the context of a prospective, single-arm pilot clinical trial, patients referred for endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high definition, white light endoscopy with narrow-band imaging (NBI). Then, CLE mapping of suspected neoplastic lesions was performed by another endoscopist, partially blinded to the previous findings, before the patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), depending on lesion size and anticipated histology., Results: In 7 of 38 patients (18 %), CLE revealed additional neoplastic tissue compared with prior white light endoscopy and NBI: 2 concomitant lesions, 2 cases of lateral tumor extension within the Barrett's epithelium, and 3 cases of previously undetected SST extension. Overall, en bloc resection (tumor-free lateral margin) was achieved in 28 of 34 neoplastic lesions (82 %), and complete resection (tumor-free lateral and basal margins) in 21 of 34 neoplastic lesions (62 %)., Conclusions: CLE-assisted endoscopic resection of BE-associated neoplasia was safe and effective in this study, as proved by a high additional diagnostic yield of CLE (including visualization of occult SST extension) and a favorable rate of en bloc resection. The clinical value of CLE for assisting endoscopic therapy of BE-associated neoplasia deserves further evaluation in randomized controlled trials.
- Published
- 2015
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38. Active pump-seed-pulse synchronization for OPCPA with sub-2-fs residual timing jitter.
- Author
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Prinz S, Häfner M, Schultze M, Teisset CY, Bessing R, Michel K, Kienberger R, and Metzger T
- Abstract
Short-pulse-pumped optical parametric chirped pulse amplification (OPCPA) requires a precise temporal overlap of the interacting pulses in the nonlinear crystal to achieve stable performance. We present active synchronization of the ps-pump pulses and the broadband seed pulses used in an OPCPA system with a residual timing jitter below 2 fs. This unprecedented stability was achieved utilizing optical parametric amplification to generate the error signal, requiring less than 4 pJ of seed- and 10 µJ of pump-pulse-energy in the optical setup. The synchronization system shows excellent long-term performance and can be easily implemented in almost any OPCPA system.
- Published
- 2014
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39. The impact of long-term health goals on sexual risk decisions in impulsive and reflective cognitive States.
- Author
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den Daas C, Häfner M, and de Wit J
- Subjects
- Cognition, Health, Humans, Male, Motivation, Surveys and Questionnaires, Decision Making, Goals, Impulsive Behavior psychology, Risk-Taking, Sexual Behavior psychology
- Abstract
In the heat of the moment, people often impulsively take risks. Having unprotected sex, for example, can result in sexually transmitted infections. In three studies, we investigated a possible explanation for the increased sexual risk propensity of people in an impulsive state. In contrast to the intuitively appealing notion that they are less influenced by their long-term goals, we hypothesized and showed that people in both impulsive and reflective states make less risky sexual decisions when health goals are important. We further showed that, when sexual health goals are important, people in a reflective state make riskier sexual decisions as temptations become stronger, while decisions of people in an impulsive state were not influenced by temptation strength. This supports the counterintuitive prediction that people in an impulsive state are better able to cope with strong temptations than people in a reflective state.
- Published
- 2014
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40. Characterization of the ovarian cycle in the two-toed sloths (Choloepus didactylus): an innovative, reliable, and noninvasive method using fecal hormone analyses.
- Author
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Troll S, Gottschalk J, Seeburger J, Ziemssen E, Häfner M, Thielebein J, and Einspanier A
- Subjects
- Animals, Female, Gonadal Steroid Hormones metabolism, Periodicity, Feces chemistry, Gonadal Steroid Hormones chemistry, Ovary physiology, Sloths physiology
- Abstract
Little is known about reproductive physiology in the two-toed sloth (Choloepus didactylus). Therefore, the aim of this study was to obtain detailed information about the ovarian cycle. Measurements of reliable gonadal steroids in the feces of this species were undertaken. For this purpose, fecal samples were collected one to three times per week from nonpregnant captive females (n = 2) over a 16-month period. Before assay analysis, the fecal samples were extracted with methanol. Radioimmunoassays and enzyme immunoassays for fecal progesterone, estradiol-17β, pregnanediol-glucuronide (PdG), and estrone sulfate were tested for their ability to detect the ovarian activity. Using the lowest and highest progesterone values, the ovarian cycle length was comparatively analyzed. The ovarian cycle (n = 26) averaged between 31.4 ± 9.1 days (lowest progesterone) and 32.5 ± 7.5 days (highest progesterone) throughout the whole year. The length of the follicular phase, as indicated by low progesterone levels, was 18.1 ± 4.4 days (range 12-25 days), and the length of the luteal phase, as characterized by elevated progesterone levels, was 13.2 ± 1.8 days (range 11-16 days). In contrast, estradiol-17β and estrone sulfate were not suitable to detect the cycle due to irregular collection intervals. Fecal progesterone and PdG, as well as estradiol-17β and estrone sulfate, significantly correlated (r = 0.621, P < 0.01 and r = 0.606, P < 0.01). PdG concentrations (dilution factor (DF) 1:40) were considerably higher than progesterone concentrations (DF 1:10), PdG amounted in the range of 1326.7 ± 320.2 ng/g wet feces (animal S1) and 1373.8 ± 468.3 ng/g wet feces (animal S2) compared with progesterone concentrations in the range of 98.0 ± 17.0 ng/g (S1) and 105.9 ± 30.0 ng/g (S2). The estrone sulfate levels (DF 1:2) were similar to estradiol-17β (DF 1:22). The mean fecal estradiol-17β concentrations were 6.7 ± 0.9 ng/g for animal S1 and 7.5 ± 1.6 ng/g for animal S2. In conclusion, the ovarian activity of the two-toed sloth was studied using the noninvasive method by means of the fecal steroid monitoring. Progesterone was the most reliable fecal steroid hormone to determine the duration of the ovarian cycle independent of the weekly defecation rate. The course of progesterone concentrations resulted in a cycle length of 4-5 weeks length in the two-toed sloth. Thus, the reproductive activity of the two-toed sloth does not show any seasonality like the three-toed sloth., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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41. Austrian consensus on the definition and treatment of portal hypertension and its complications (Billroth II).
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Peck-Radosavljevic M, Angermayr B, Datz C, Ferlitsch A, Ferlitsch M, Fuhrmann V, Häfner M, Kramer L, Maieron A, Payer B, Reiberger T, Stauber R, Steininger R, Trauner M, Thurnher S, Ulbrich G, Vogel W, Zoller H, and Graziadei I
- Subjects
- Esophageal and Gastric Varices etiology, Gastrointestinal Hemorrhage etiology, Humans, Hypertension, Portal complications, Esophageal and Gastric Varices diagnosis, Esophageal and Gastric Varices therapy, Gastroenterology standards, Gastrointestinal Hemorrhage diagnosis, Gastrointestinal Hemorrhage therapy, Hypertension, Portal diagnosis, Hypertension, Portal therapy
- Abstract
In November 2004, the Austrian Society of Gastroenterology and Hepatology (ÖGGH) held for the first time a consensus meeting on the definitions and treatment of portal hypertension and its complications in the Billroth-Haus in Vienna, Austria (Billroth I-Meeting). This meeting was preceded by a meeting of international experts on portal hypertension with some of the proponents of the Baveno consensus conferences (http://www.oeggh.at/videos.asp). The consensus itself is based on the Baveno III consensus with regard to portal hypertensive bleeding and the suggestions of the International Ascites Club regarding the treatment of ascites. Those statements were modified by new knowledge derived from the recent literature and also by the current practice of medicine as agreed upon by the participants of the consensus meeting. In October 2011, the ÖGGH organized the second consensus meeting on portal hypertension and its complications in Vienna (Billroth II-Meeting). The Billroth II-Guidelines on the definitions and treatment of portal hypertension and its complications take into account the developments of the last 7 years, including the Baveno-V update and several key publications.
- Published
- 2013
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42. Gastrointestinal stromal tumors: diagnosis, therapy and follow-up care in Austria.
- Author
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Bareck E, Ba-Ssalamah A, Brodowicz T, Eisterer W, Häfner M, Högenauer C, Kastner U, Kühr T, Längle F, Liegl-Atzwanger B, Schoppmann SF, Widmann G, Wrba F, Zacherl J, and Ploner F
- Subjects
- Adult, Austria, Benzamides therapeutic use, Biopsy, Child, Combined Modality Therapy, Cooperative Behavior, Diagnosis, Differential, Diagnostic Imaging, Disease Progression, Endoscopy, Gastrointestinal, Follow-Up Studies, Gastrointestinal Neoplasms genetics, Gastrointestinal Neoplasms pathology, Gastrointestinal Stromal Tumors genetics, Gastrointestinal Stromal Tumors pathology, Gastrointestinal Tract pathology, Gastrointestinal Tract surgery, Humans, Imatinib Mesylate, Indoles therapeutic use, Interdisciplinary Communication, Mitotic Index, Neoadjuvant Therapy, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Neoplasm Staging, Neoplasms, Multiple Primary diagnosis, Neoplasms, Multiple Primary pathology, Neoplasms, Multiple Primary surgery, Nomograms, Palliative Care, Phenylurea Compounds therapeutic use, Piperazines therapeutic use, Proto-Oncogene Proteins c-kit genetics, Pyridines therapeutic use, Pyrimidines therapeutic use, Pyrroles therapeutic use, Randomized Controlled Trials as Topic, Risk Assessment, Sunitinib, Aftercare, Gastrointestinal Neoplasms diagnosis, Gastrointestinal Neoplasms surgery, Gastrointestinal Stromal Tumors diagnosis, Gastrointestinal Stromal Tumors surgery
- Abstract
Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.
- Published
- 2013
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43. When body and mind are talking. Interoception moderates embodied cognition.
- Author
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Häfner M
- Subjects
- Awareness, Female, Humans, Male, Young Adult, Cognition physiology, Discrimination, Psychological physiology, Judgment physiology, Mind-Body Relations, Metaphysical, Perception physiology
- Abstract
Recent research on so-called embodied cognitions strengthens the current view that the body and the mind cannot be separated in producing cognitions. But how and when does the body talk to the mind? Drawing on the notion that bodily processes are transformed into mental action through experiences, it is argued that embodied cognitions should be moderated by interindividual differences in the sensitivity to stimuli originating inside of the body, that is, by interoception. In line with these assumptions, two experiments demonstrate that the embodiment of weight and softness in value judgments and person impressions is moderated by interoception as assessed by a body-awareness questionnaire (Experiment 1) and a heartbeat perception task (Experiment 2). Taken together, these findings strongly speak to the notion that bodily processes and the experience thereof play an important role in embodiment, thereby extending previous research above and beyond the mere demonstration of body-mind interactions.
- Published
- 2013
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44. Prophylaxis of acute radiation dermatitis with an innovative FDA-approved two-step skin care system in a patient with head and neck cancer undergoing a platin-based radiochemotherapy: a case report and review of the literature.
- Author
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Häfner MF, Fetzner L, Hassel JC, Debus J, and Potthoff K
- Subjects
- Acute Disease, Chemoradiotherapy adverse effects, Device Approval, Female, Humans, Middle Aged, Radiodermatitis etiology, Squamous Cell Carcinoma of Head and Neck, Antineoplastic Agents therapeutic use, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms therapy, Radiodermatitis prevention & control, Skin Care instrumentation
- Abstract
Radiodermatitis is a very common side effect in cancer treatment often leading to therapy delays and diminution of the patients' health state and quality of life. Despite a wide range of supportive strategies, radiodermatitis is still a major problem necessitating further improvements in prevention and treatment. Lactokine is a milk-based protein shown to assist in the reduction of skin redness. The treatment is a unique FDA-approved skin care system (R1 and R2). In this case presentation we describe the prophylactic use of R1 and R2 in a 63-year-old, female patient with a squamous cell carcinoma of the hypopharynx undergoing a platin-based chemoradiation. The application was feasible and safe and the patient developed only a slight radiodermatitis. To our knowledge this is the first report in the literature on the prophylactic use of R1 and R2. Further evidence will be provided by a prospective, clinical trial we have launched (CREAM-1; study registration in ISRCTN Registry: ISRCTN87302591). We also review the literature to give an overview about common strategies in the management of radiodermatitis.
- Published
- 2013
- Full Text
- View/download PDF
45. Out of sight, out of mind: cognitive states alter the focus of attention.
- Author
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den Daas C, Häfner M, and de Wit J
- Subjects
- Eye Movement Measurements, Female, Humans, Impulsive Behavior, Judgment, Male, Motivation, Photography, Young Adult, Attention physiology, Cognition physiology
- Abstract
People in an impulsive state are influenced mainly by the immediate incentive value of appetitive stimuli, whereas people in a reflective state usually also consider the (sometimes negative) long-term consequences of such stimuli. In order to consider all information, we hypothesize that, people in reflective states distribute their attention over all available information, whereas people in impulsive states focus their attention on the most salient information. We measured cognitive states using eye-blink rate (Experiment 1) or induced them with a procedural priming manipulation (Experiments 2 and 3). In eye-tracking Experiments 1 and 2, we established that people in an impulsive state indeed focus their attention on the salient information, whereas people in a reflective state distribute their attention. Moreover, we show that this attentional difference extends to evaluative judgments (Experiment 3), which could potentially contribute to people's increased propensity to risk in impulsive states.
- Published
- 2013
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46. Endoscopic image analysis in semantic space.
- Author
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Kwitt R, Vasconcelos N, Rasiwasia N, Uhl A, Davis B, Häfner M, and Wrba F
- Subjects
- Humans, Image Enhancement methods, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Artificial Intelligence, Endoscopy methods, Image Interpretation, Computer-Assisted methods, Imaging, Three-Dimensional methods, Pattern Recognition, Automated methods
- Abstract
A novel approach to the design of a semantic, low-dimensional, encoding for endoscopic imagery is proposed. This encoding is based on recent advances in scene recognition, where semantic modeling of image content has gained considerable attention over the last decade. While the semantics of scenes are mainly comprised of environmental concepts such as vegetation, mountains or sky, the semantics of endoscopic imagery are medically relevant visual elements, such as polyps, special surface patterns, or vascular structures. The proposed semantic encoding differs from the representations commonly used in endoscopic image analysis (for medical decision support) in that it establishes a semantic space, where each coordinate axis has a clear human interpretation. It is also shown to establish a connection to Riemannian geometry, which enables principled solutions to a number of problems that arise in both physician training and clinical practice. This connection is exploited by leveraging results from information geometry to solve problems such as (1) recognition of important semantic concepts, (2) semantically-focused image browsing, and (3) estimation of the average-case semantic encoding for a collection of images that share a medically relevant visual detail. The approach can provide physicians with an easily interpretable, semantic encoding of visual content, upon which further decisions, or operations, can be naturally carried out. This is contrary to the prevalent practice in endoscopic image analysis for medical decision support, where image content is primarily captured by discriminative, high-dimensional, appearance features, which possess discriminative power but lack human interpretability., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
47. Delaunay triangulation-based pit density estimation for the classification of polyps in high-magnification chromo-colonoscopy.
- Author
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Häfner M, Liedlgruber M, Uhl A, Vécsei A, and Wrba F
- Subjects
- Aged, Algorithms, Automation, Colonic Polyps pathology, Computer Simulation, Endoscopes, Endoscopy methods, Humans, Image Processing, Computer-Assisted methods, Medical Informatics, Middle Aged, Models, Statistical, Normal Distribution, Pattern Recognition, Automated methods, Polyps, Reproducibility of Results, Colonic Polyps diagnosis, Colonoscopy methods
- Abstract
In this work we propose a method to extract shape-based features from endoscopic images for an automated classification of colonic polyps. This method is based on the density of pits as used in the pit pattern classification scheme which is commonly used for the classification of colonic polyps. For the detection of pits we employ a noise-robust variant of the LBP operator. To be able to be robust against local texture variations we extend this operator by an adaptive thresholding. Based on the detected pit candidates we compute a Delaunay triangulation and use the edge lengths of the resulting triangles to construct histograms. These are then used in conjunction with the k-NN classifier to classify images. We show that, compared to a previously developed method, we are not only able to almost always get higher classification results in our application scenario, but that the proposed method is also able to significantly outperform the previously developed method in terms of the computational demand., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
- Full Text
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48. Approach/Avoidance Orientations Affect Self-Construal and Identification with In-group.
- Author
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Nussinson R, Häfner M, Seibt B, Strack F, and Trope Y
- Abstract
Approach and avoidance are two basic motivational orientations. Their activation influences cognitive and perceptive processes: Previous work suggests that an approach orientation instigates a focus on larger units as compared to avoidance. Study 1 confirms this assumption using a paradigm that more directly taps a person's tendency to represent objects as belonging to small or large units than prior studies. It was further predicted that the self should also be represented as belonging to larger units, and hence be more interdependent under approach than under avoidance. Study 2 supports this prediction. As a consequence of this focus on belonging to larger units, it was finally predicted that approach results in a stronger identification with one's in-group than avoidance. Studies 3 and 4 support that prediction.
- Published
- 2012
- Full Text
- View/download PDF
49. [Highlights in gastroenterology 2011].
- Author
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Schwizer W, Rogler G, Rösch T, Bauerfeind P, Häfner M, Wirth HP, Müllhaupt B, and Fried M
- Subjects
- Curriculum, Hospitals, University, Humans, Switzerland, Education, Medical, Continuing, Gastroenterology education
- Abstract
«Gastro-Highlights», an annual symposium dedicated to continuing education, took place at the University Hospital Zürich for the sixteenth time this autumn. In this well-attended event, major new findings in the fields of gastroenterology and hepatology that were published in the past year or recently presented at the «Digestive Disease Week (DDW)» were summarized for practising gastroenterologists and internists.
- Published
- 2012
- Full Text
- View/download PDF
50. Color treatment in endoscopic image classification using multi-scale local color vector patterns.
- Author
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Häfner M, Liedlgruber M, Uhl A, Vécsei A, and Wrba F
- Subjects
- Artificial Intelligence, Humans, Image Enhancement methods, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Colonic Polyps pathology, Color, Colorimetry methods, Endoscopy, Gastrointestinal methods, Image Interpretation, Computer-Assisted methods, Pattern Recognition, Automated methods
- Abstract
In this work we propose a novel method to describe local texture properties within color images with the aim of automated classification of endoscopic images. In contrast to comparable Local Binary Patterns operator approaches, where the respective texture operator is almost always applied to each color channel separately, we construct a color vector field from an image. Based on this field the proposed operator computes the similarity between neighboring pixels. The resulting image descriptor is a compact 1D-histogram which we use for a classification using the k-nearest neighbors classifier. To show the usability of this operator we use it to classify magnification-endoscopic images according to the pit pattern classification scheme. Apart from that, we also show that compared to previously proposed operators we are not only able to get competitive classification results in our application scenario, but that the proposed operator is also able to outperform the other methods either in terms of speed, feature compactness, or both., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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