Introduction: Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where... Show moreIntroduction: Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where pathologic diagnosis has been essentially limited to three histologic subtypes.Methods: A multidisciplinary group (pathologists, molecular biologists, surgeons, radiologists, and oncologists), sponsored by European Network for Rare Adult Solid Cancers/International Association for the Study of Lung Cancer, met in 2018 to critically review the current classification.Results: Recommendations include: (1) classification should be updated to include architectural patterns and stromal and cytologic features that refine prognostication; (2) subject to data accrual, malignant mesothelioma in situ could be an additional category; (3) grading of epithelioid malignant pleural mesotheliomas should be routinely undertaken; (4) favorable/unfavorable histologic characteristics should be routinely reported; (5) clinically relevant molecular data (programmed death ligand 1, BRCA 1 associated protein 1 [BAP1], and cyclin dependent kinase inhibitor 2A) should be incorporated into reports, if undertaken; (6) other molecular data should be accrued as part of future trials; (7) resection specimens (i.e., extended pleurectomy/decortication and extrapleural pneumonectomy) should be pathologically staged with smaller specimens being clinically staged; (8) ideally, at least three separate areas should be sampled from the pleural cavity, including areas of interest identified on pre-surgical imaging; (9) image-acquisition protocols/imaging terminology should be standardized to aid research/refine clinical staging; (10) multidisciplinary tumor boards should include pathologists to ensure appropriate treatment options are considered; (11) all histologic subtypes should be considered potential candidates for chemotherapy; (12) patients with sarcomatoid or biphasic mesothelioma should not be excluded from first-line clinical trials unless there is a compelling reason; (13) tumor subtyping should be further assessed in relation to duration of response to immunotherapy; and (14) systematic screening of all patients for germline mutations is not recommended, in the absence of a family history suspicious for BAP1 syndrome.Conclusions: These multidisciplinary recommendations for pathology classification and application will allow more informative pathologic reporting and potential risk stratification, to support clinical practice, research investigation and clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. Show less
Vos, F. de; Schouten, T.M.; Koini, M.; Bouts, M.J.R.J.; Feis, R.A.; Lechner, A.; ... ; Rombouts, S.A.R.B. 2020
Anatomical magnetic resonance imaging (MRI), diffusion MRI and resting state functional MRI (rs-fMRI) have been used for Alzheimer's disease (AD) classification. These scans are typically used to... Show moreAnatomical magnetic resonance imaging (MRI), diffusion MRI and resting state functional MRI (rs-fMRI) have been used for Alzheimer's disease (AD) classification. These scans are typically used to build models for discriminating AD patients from control subjects, but it is not clear if these models can also discriminate AD in diverse clinical populations as found in memory clinics.To study this, we trained MRI-based AD classification models on a single centre data set consisting of AD patients (N = 76) and controls (N = 173), and used these models to assign AD scores to subjective memory complainers (N = 67), mild cognitive impairment (MCI) patients (N = 61), and AD patients (N = 61) from a multi-centre memory clinic data set. The anatomical MRI scans were used to calculate grey matter density, subcortical volumes and cortical thickness, the diffusion MRI scans were used to calculate fractional anisotropy, mean, axial and radial diffusivity, and the rs-fMRI scans were used to calculate functional connectivity between resting state networks and amplitude of low frequency fluctuations. Within the multi-centre memory clinic data set we removed scan site differences prior to applying the models.For all models, on average, the AD patients were assigned the highest AD scores, followed by MCI patients, and later followed by SMC subjects. The anatomical MRI models performed best, and the best performing anatomical MRI measure was grey matter density, separating SMC subjects from MCI patients with an AUC of 0.69, MCI patients from AD patients with an AUC of 0.70, and SMC patients from AD patients with an AUC of 0.86. The diffusion MRI models did not generalise well to the memory clinic data, possibly because of large scan site differences. The functional connectivity model separated SMC subjects and MCI patients relatively good (AUC = 0.66). The multimodal MRI model did not improve upon the anatomical MRI model.In conclusion, we showed that the grey matter density model generalises best to memory clinic subjects. When also considering the fact that grey matter density generally performs well in AD classification studies, this feature is probably the best MRI-based feature for AD diagnosis in clinical practice. Show less
It has been argued that the Internet presents numerous new opportunities for crime, including homicide. So far, empirical scholarly research in this domain is rather limited. In order to discover... Show moreIt has been argued that the Internet presents numerous new opportunities for crime, including homicide. So far, empirical scholarly research in this domain is rather limited. In order to discover how perpetrators have used the Internet in the homicides they have committed, we conducted an international newspaper search (2006–2017). Based on this analysis, we identify five distinct types of Internet use in homicides, namely Internet as an encyclopedia, Internet as a platform, Internet as a trigger, Internet as a market place, and Internet as a meeting place. Our findings indicate that these types do not significantly differ from key characteristics of homicides in general to the degree that they constitute unique forms of homicide. Rather, Internet-related homicides constitute a replication, or facilitation of already existing forms of homicide assisted through new technological means. Show less
The main objectives of therapeutic trials in venous thromboembolism (VTE) are to prevent recurrent VTE, major bleeding and death. While these outcomes are indeed highly relevant, they are also rare... Show moreThe main objectives of therapeutic trials in venous thromboembolism (VTE) are to prevent recurrent VTE, major bleeding and death. While these outcomes are indeed highly relevant, they are also rare and do not fully capture the overall functional outcome of VTE patients. Importantly, functional limitations after VTE are prevalent after both deep vein thrombosis and pulmonary embolism occurring in up to 50% of patients. These post-VTE syndromes are associated with a decreased quality of life, higher risk of depressive disorders, unemployment and increased utilization of healthcare resources. Because of the major impact of functional limitations on individual patients and society as a whole, development of tools able to capture functional outcomes in clinical trials are urgently needed. We anticipate that a standardized post-VTE functional status scale will aid in demarcating effective and ineffective VTE therapies on functional outcomes in trials with appropriately powered sample sizes, as well as pave the road for value-based healthcare. The scale that we have in mind covers the entire spectrum of functional outcomes ranging from no symptoms to death. Moreover, it focuses on both limitations in usual activity as well as changes in lifestyle. The scale is not meant to replace current diagnostic or prognostic scores for post-VTE syndromes, but to be used as an outcome measure to evaluate the overall consequences of VTE on functional status. This review is a call for action to the VTE community to join forces and support further development of the proposed scale, a process of which we summarize the necessary steps. Show less
Our current mycosis fungoides (MF) and Sezary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sezary counts but results... Show moreOur current mycosis fungoides (MF) and Sezary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sezary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry.No large study comparing blood-class as defined by Sezary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis.For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4thornCD7-or CD4+CD26- where B0<250/mu L, B1 = 250/mu l -<1000/mu L and B2 >= 1000/mu L plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known. (C) 2018 The Authors. Published by Elsevier Ltd. Show less
Vos, F. de; Koini, M.; Schouten, T.M.; Seiler, S.; Grond, J. van der; Lechner, A.; ... ; Rombouts, S.A.R.B. 2018
Alzheimer's disease (AD) patients show altered patterns of functional connectivity (FC) on resting state functional magnetic resonance imaging (RSfMRI) scans. It is yet unclear which RSfMRI... Show moreAlzheimer's disease (AD) patients show altered patterns of functional connectivity (FC) on resting state functional magnetic resonance imaging (RSfMRI) scans. It is yet unclear which RSfMRI measures are most informative for the individual classification of AD patients. We investigated this using RSfMRI scans from 77 AD patients (MMSE = 20.4 ± 4.5) and 173 controls (MMSE = 27.5 ± 1.8). We calculated i) FC matrices between resting state components as obtained with independent component analysis (ICA), ii) the dynamics of these FC matrices using a sliding window approach, iii) the graph properties (e.g., connection degree, and clustering coefficient) of the FC matrices, and iv) we distinguished five FC states and administered how long each subject resided in each of these five states. Furthermore, for each voxel we calculated v) FC with 10 resting state networks using dual regression, vi) FC with the hippocampus, vii) eigenvector centrality, and viii) the amplitude of low frequency fluctuations (ALFF). These eight measures were used separately as predictors in an elastic net logistic regression, and combined in a group lasso logistic regression model. We calculated the area under the receiver operating characteristic curve plots (AUC) to determine classification performance. The AUC values ranged between 0.51 and 0.84 and the highest were found for the FC matrices (0.82), FC dynamics (0.84) and ALFF (0.82). The combination of all measures resulted in an AUC of 0.85. We show that it is possible to obtain moderate to good AD classification using RSfMRI scans. FC matrices, FC dynamics and ALFF are most discriminative and the combination of all the resting state measures improves classification accuracy slightly. Show less
Boesveld, I.C.; Bruijnzeels, M.A.; Hitzert, M.; Hermus, M.A.A.; Pal-de Bruin, K.M. van der; Akker-van Marle, M.E. van den; ... ; Wiegers, T.A. 2017
We propose a novel classification method that integrates into existing agile software development practices by collecting data records generated by software and tools used in the development... Show moreWe propose a novel classification method that integrates into existing agile software development practices by collecting data records generated by software and tools used in the development process. We extract features from the collected data and create visualizations that provide insights, and feed the data into a prediction framework consisting of a deep neural network. The features and results are validated against conceptual frameworks that model the development methodologies as similar processes in other contexts. Initial results show that the visualization and prediction techniques provide promising outcomes that may help development teams and management gain better understanding of past events and future risks. Show less
De belangrijkste resultaten van dit proefschrift: de ASAS classificatie criteria voor axSpA blijken robuust en zijn goed toepasbaar in een setting waarbij de waarschijnlijkheid op axSpA lager is... Show moreDe belangrijkste resultaten van dit proefschrift: de ASAS classificatie criteria voor axSpA blijken robuust en zijn goed toepasbaar in een setting waarbij de waarschijnlijkheid op axSpA lager is dan waarin de criteria ontwikkeld zijn. Daarnaast is er op basis van bevindingen in dit proefschrift een belangrijke aanpassing doorgevoerd in een hulpmiddel dat reumatologen begeleidt in het diagnostische proces van (vroege) axSpA. Tevens is het MRI protocol van het SPACE cohort aangepast nadat de toegevoegde waarde van het toedienen van een contrastvloeistof bij het maken van MRI’s nihil bleek te zijn, met als resultaat dat er sinds april 2012 geen MRI’s meer worden gemaakt met de toediening van gadolinium. Dit proefschrift biedt ook adequate handvatten voor verder onderzoek naar de optimale definitie van een positieve MRI. Bovendien worden discrepanties aangaande de beoordeling door verschillende soorten lezers van afwijkingen in de rug (op röntgenfoto’s en MRI’s) aan het licht gebracht waardoor de vraag naar voren komt of training in het onderscheiden van axSpA afwijkingen en afwijkingen die niet gerelateerd zijn aan axSpA van potentiële belang is op de betrouwbaarheid van het beoordelen van afwijkingen in de rug. De onderzoeken in dit proefschrift leveren een bijdrage aan betere herkenning en behandeling van axSpA. Show less
Magnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease.... Show moreMagnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N = 77) from the prospective registry on dementia study and controls (N = 173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification. (C) 2016 The Authors. Published by Elsevier Inc. Show less
