Pan-European Sarcoma Trials: Moving Forward in a Climate of Increasing Economic and Regulatory Pressure

Advances in sarcoma treatment are largely based on investigator-initiated, multicentric and interdisciplinary clinical trials. The EU's Good Clinical Practice Directive 2001/20/EC, effective since 2004, was meant to harmonize the conditions for clinical trials across Europe, but, instead, the challenge of initiating and running multinational, noncommercial clinical trials has become greater than ever. Institutions participating in existing noncommercial Pan-European studies are struggling to cope with increased administrative and financial burdens, and few new studies are initiated any more. The aim of a conference entitled “Pan-European Sarcoma Trials: Moving Forward in a Climate of Increasing Economic and Regulatory Pressure,” held in Stuttgart, Germany, 30 November–2 December 2006 as part of the European Science Foundation's ECT-program, was not only to provide an overview of currently active and planned multinational studies on osteo-, Ewing's, and soft tissue sarcoma, but also to draw on areas of synergy between various established sarcoma groups in Europe to define plausible survival strategies for collaborative, interdisciplinary, patient-oriented research

Generation of synthetic EEG data for training algorithms supporting the diagnosis of major depressive disorder

IntroductionMajor depressive disorder (MDD) is the most common mental disorder worldwide, leading to impairment in quality and independence of life. Electroencephalography (EEG) biomarkers processed with machine learning (ML) algorithms have been explored for objective diagnoses with promising results. However, the generalizability of those models, a prerequisite for clinical application, is restricted by small datasets. One approach to train ML models with good generalizability is complementing the original with synthetic data produced by generative algorithms. Another advantage of synthetic data is the possibility of publishing the data for other researchers without risking patient data privacy. Synthetic EEG time-series have not yet been generated for two clinical populations like MDD patients and healthy controls.MethodsWe first reviewed 27 studies presenting EEG data augmentation with generative algorithms for classification tasks, like diagnosis, for the possibilities and shortcomings of recent methods. The subsequent empirical study generated EEG time-series based on two public datasets with 30/28 and 24/29 subjects (MDD/controls). To obtain baseline diagnostic accuracies, convolutional neural networks (CNN) were trained with time-series from each dataset. The data were synthesized with generative adversarial networks (GAN) consisting of CNNs. We evaluated the synthetic data qualitatively and quantitatively and finally used it for re-training the diagnostic model.ResultsThe reviewed studies improved their classification accuracies by between 1 and 40% with the synthetic data. Our own diagnostic accuracy improved up to 10% for one dataset but not significantly for the other. We found a rich repertoire of generative models in the reviewed literature, solving various technical issues. A major shortcoming in the field is the lack of meaningful evaluation metrics for synthetic data. The few studies analyzing the data in the frequency domain, including our own, show that only some features can be produced truthfully.DiscussionThe systematic review combined with our own investigation provides an overview of the available methods for generating EEG data for a classification task, their possibilities, and shortcomings. The approach is promising and the technical basis is set. For a broad application of these techniques in neuroscience research or clinical application, the methods need fine-tuning facilitated by domain expertise in (clinical) EEG research

Lateral dynamics simulation of webs having cross-machine direction variation

Webs often include sectional variation in caliper or modulus of elasticity as a result of undesirable manufacturing variation or by intentional design. These variations influence wrinkle formation and tracking control in multi-span web handling systems. This paper shares the results of finite element simulations of the lateral dynamics of webs having variation in thickness and modulus in cross-machine direction. Span length and machine-direction bulk strain were varied and the effects on lateral steering and wrinkle formation were simulated for a variety of inhomogeneous webs.Key variables affecting the lateral steering include the CMD location of the thick section and its width, the stiffness of the thick section, the z-direction bias of the thick section relative to the roller surface, the average strain in the composite web and the span length/width ratio. The web shifted in most cases toward the half of the web having the thick section, though not all. The combination of a web with a thick, stiff section having a width 1/10-1/6 that of the base web, coincident with the web edge, in long spans with low strain generated the largest lateral shift. Wrinkles were generated for some conditions where the thick section was located on or near web centerline

Impacts of a 90 degree twist on lateral web dynamics

Twists are sometimes used to turn or provide passive lateral control for narrow webs in those cases where space for a sufficient twist span length (to avoid a wrinkle) is achievable. This paper uses the finite element method to study the lateral dynamics of a web downstream of a 90 degree twist in response to an upstream lateral disturbance. A designed experiment of 46 different finite element runs was used to study the interactions among different material, geometry, and input variables. Specifically, the frequency response for downstream cross-direction position was modeled as a function of the disturbance frequency, disturbance amplitude, span length, wrap angle and material stiffness. Nominal strain was held constant. A composite Gaussian process model was fit to the resulting data to facilitate a deeper and more holistic interpretation. Excellent attenuation of the disturbance amplitude and interesting interactions with the applied frequency and twist span length were shown

Wrinkling mechanisms of webs with spatially varying material properties

Webs often include variation in caliper or modulus of elasticity as a result of manufacturing variation. Light-weight nonwoven webs are especially prone to these issues because the variation is proportionally more, relative to the average modulus. It is proposed that the length scale variability in fiber orientation and most importantly mass density extends to the mechanical properties of the web, including the degree of orthotropy and Poisson's ratio (neckdown behavior). Finite element simulations show that materials exhibiting this kind of variability (in MD and CMD modulus, and Poisson's ratio), notably with nominally high and low regions alternating in the MD, leads to trough and wrinkle formation. Multiple simulations with varied material properties have led to a greater understanding of the mechanisms and conditions that cause these types of wrinkles

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols

Background: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. Patients and methods: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. Results: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. Conclusions: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the futur

Gender Roles in \u27Sleeping Beauty\u27 (1959)

I first planned out my argument with evidence from the film so I had a thesis to work with, and then I structured my body paragraphs. I spent most of my time writing and organizing the evidence and research I found to support my argument in the most effective way. When I was content with the structure and ideas of my argument, I worked on my introduction and conclusion. In my introduction, I contextualized my discussion of gender roles in Sleeping Beauty (1959) with the gender roles in America at the time of the film, and with my conclusion, I tried to assert the importance of analyzing the gender roles in fairy tales like Sleeping Beauty (1959)