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Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Contains fulltext : 245053.pdf (Publisher’s version ) (Open Access), BACKGROUND: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. METHODS: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. RESULTS: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. CONCLUSIONS: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

Contains fulltext : 244124.pdf (Publisher’s version ) (Open Access), BACKGROUND: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. OBJECTIVE: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. METHODS: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). RESULTS: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. CONCLUSIONS: Return of individual PRO results seems to meet patients' wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation wa

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Contains fulltext : 245053.pdf (Publisher’s version ) (Open Access), BACKGROUND: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. METHODS: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. RESULTS: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. CONCLUSIONS: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

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Contains fulltext : 244124.pdf (Publisher’s version ) (Open Access), BACKGROUND: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. OBJECTIVE: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. METHODS: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). RESULTS: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. CONCLUSIONS: Return of individual PRO results seems to meet patients' wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed

Item does not contain fulltext

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Contains fulltext : 245053.pdf (Publisher’s version ) (Open Access), BACKGROUND: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. METHODS: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. RESULTS: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. CONCLUSIONS: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

Reinforcement learning algorithms have proven to be capable of solving complicated robotics tasks in an end-to-end fashion without any need for hand-crafted features or policies. Especially in the context of robotics, in which the cost of real-world data is usually extremely high, Reinforcement Learning solutions achieving high sample efficiency are needed. In this paper, we propose a framework combining the learning of a low-dimensional state representation, from high-dimensional observations coming from the robot's raw sensory readings, with the learning of the optimal policy, given the learned state representation. We evaluate our framework in the context of mobile robot navigation in the case of continuous state and action spaces. Moreover, we study the problem of transferring what learned in the simulated virtual environment to the real robot without further retraining using real-world data in the presence of visual and depth distractors, such as lighting changes and moving obstacles. A video of our experiments can be found at: https://youtu.be/rUdGPKr2Wuo.

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.

Multiple sclerosis is a chronic inflammatory, demyelinating disease, although it has been suggested that in the progressive late phase, inflammatory lesion activity declines. We recently showed in the Netherlands Brain Bank multiple sclerosis-autopsy cohort considerable ongoing inflammatory lesion activity also at the end stage of the disease, based on microglia/macrophage activity. We have now studied the role of T cells in this ongoing inflammatory lesion activity in chronic multiple sclerosis autopsy cases. We quantified T cells and perivascular T-cell cuffing at a standardized location in the medulla oblongata in 146 multiple sclerosis, 20 neurodegenerative control and 20 non-neurological control brain donors. In addition, we quantified CD3+, CD4+, and CD8+ T cells in 140 subcortical white matter lesions. The location of CD8+ T cells in either the perivascular space or the brain parenchyma was determined using CD8/laminin staining and confocal imaging. Finally, we analysed CD8+ T cells, isolated from fresh autopsy tissues from subcortical multiple sclerosis white matter lesions (n = 8), multiple sclerosis normal-app

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reinforcement Learning has been able to solve many complicated robotics tasks without any need for feature engineering in an end-to-end fashion. However, learning the optimal policy directly from the sensory inputs, i.e the observations, often requires processing and storage of a huge amount of data. In the context of robotics, the cost of data from real robotics hardware is usually very high, thus solutions that achieve high sample-efficiency are needed. We propose a method that aims at learning a mapping from the observations into a lower-dimensional state space. This mapping is learned with unsupervised learning using loss functions shaped to incorporate prior knowledge of the environment and the task. Using the samples from the state space, the optimal policy is quickly and efficiently learned. We test the method on several mobile robot navigation tasks in a simulation environment and also on a real robot. A video of our experiments can be found at: https://youtu.be/dgWxmfSv95U.

In this research, we investigate the use of Reinforcement Learning (RL) for an effective and robust solution for exploring unknown and indoor environments and reconstructing their maps. We benefit from a Simultaneous Localization and Mapping (SLAM) algorithm for real-time robot localization and mapping. Three different reward functions are compared and tested in different environments with growing complexity. The performances of the three different RL-based path planners are assessed not only on the training environments, but also on an a priori unseen environment to test the generalization properties of the policies. The results indicate that RL-based planners trained to maximize the coverage of the map are able to consistently explore and construct the maps of different indoor environments.

Item does not contain fulltext, BACKGROUND: The IDEAL DVT study showed that it was safe to shorten the duration of elastic compression therapy on an individualised basis after deep vein thrombosis for prevention of post-thrombotic syndrome. In this study, we assessed the cost-effectiveness of this strategy. METHODS: IDEAL DVT was a multicentre, randomised, non-inferiority trial that included patients with acute proximal deep vein thrombosis of the leg. After 6 months of elastic compression therapy, patients were randomly assigned (1:1) to the standard 2 years of elastic stocking compression therapy or shortened duration of compression therapy based on the patient's Villalta score. For our cost-effectiveness analysis, we assessed quality-adjusted life-years (QALYs), measured with the three-level version of EQ-5D (EQ-5D-3L; Dutch and UK tariff) and the 36-item Short Form Health Survey (SF-36), and costs in euro (health-care and societal perspective) according to the intention-to-treat approach. Data were collected at 3, 6, 12, and 24 months after diagnosis of thrombosis. We calculated incremental net monetary benefit using a QALY threshold of euro30 000, and obtained bootstrapped means and 95% CIs. IDEAL DVT is registered with ClinicalTrials.gov, number NCT01429714. FINDINGS: Between March 22, 2011, and July 1, 2015, 865 patients were enrolled in IDEAL DVT. 437 were assigned to individualised duration of elastic compression therapy and 428 to standard duration of elastic compression therapy. Nine patients were eventually excluded because of recurrent venous thromboembolism within 6 months after the first event. From a societal perspective, for every QALY lost measured with the EQ-5D Dutch tariff, cost savings were euro305.992 (incremental net monetary benefit euro3205, 95% CI 502-5741), and for every QALY lost based on the Short-Form Six-Dimension (SF-6D) utility score (derived from SF-36), cost savings were euro6030.941 (euro3540, 95% CI 1174-5953). Using the UK tariff for EQ-5D, the individualised

Item does not contain fulltext, BACKGROUND: The IDEAL DVT study showed that it was safe to shorten the duration of elastic compression therapy on an individualised basis after deep vein thrombosis for prevention of post-thrombotic syndrome. In this study, we assessed the cost-effectiveness of this strategy. METHODS: IDEAL DVT was a multicentre, randomised, non-inferiority trial that included patients with acute proximal deep vein thrombosis of the leg. After 6 months of elastic compression therapy, patients were randomly assigned (1:1) to the standard 2 years of elastic stocking compression therapy or shortened duration of compression therapy based on the patient's Villalta score. For our cost-effectiveness analysis, we assessed quality-adjusted life-years (QALYs), measured with the three-level version of EQ-5D (EQ-5D-3L; Dutch and UK tariff) and the 36-item Short Form Health Survey (SF-36), and costs in euro (health-care and societal perspective) according to the intention-to-treat approach. Data were collected at 3, 6, 12, and 24 months after diagnosis of thrombosis. We calculated incremental net monetary benefit using a QALY threshold of euro30 000, and obtained bootstrapped means and 95% CIs. IDEAL DVT is registered with ClinicalTrials.gov, number NCT01429714. FINDINGS: Between March 22, 2011, and July 1, 2015, 865 patients were enrolled in IDEAL DVT. 437 were assigned to individualised duration of elastic compression therapy and 428 to standard duration of elastic compression therapy. Nine patients were eventually excluded because of recurrent venous thromboembolism within 6 months after the first event. From a societal perspective, for every QALY lost measured with the EQ-5D Dutch tariff, cost savings were euro305.992 (incremental net monetary benefit euro3205, 95% CI 502-5741), and for every QALY lost based on the Short-Form Six-Dimension (SF-6D) utility score (derived from SF-36), cost savings were euro6030.941 (euro3540, 95% CI 1174-5953). Using the UK tariff for EQ-5D, the individualised

Item does not contain fulltext, BACKGROUND: The IDEAL DVT study showed that it was safe to shorten the duration of elastic compression therapy on an individualised basis after deep vein thrombosis for prevention of post-thrombotic syndrome. In this study, we assessed the cost-effectiveness of this strategy. METHODS: IDEAL DVT was a multicentre, randomised, non-inferiority trial that included patients with acute proximal deep vein thrombosis of the leg. After 6 months of elastic compression therapy, patients were randomly assigned (1:1) to the standard 2 years of elastic stocking compression therapy or shortened duration of compression therapy based on the patient's Villalta score. For our cost-effectiveness analysis, we assessed quality-adjusted life-years (QALYs), measured with the three-level version of EQ-5D (EQ-5D-3L; Dutch and UK tariff) and the 36-item Short Form Health Survey (SF-36), and costs in euro (health-care and societal perspective) according to the intention-to-treat approach. Data were collected at 3, 6, 12, and 24 months after diagnosis of thrombosis. We calculated incremental net monetary benefit using a QALY threshold of euro30 000, and obtained bootstrapped means and 95% CIs. IDEAL DVT is registered with ClinicalTrials.gov, number NCT01429714. FINDINGS: Between March 22, 2011, and July 1, 2015, 865 patients were enrolled in IDEAL DVT. 437 were assigned to individualised duration of elastic compression therapy and 428 to standard duration of elastic compression therapy. Nine patients were eventually excluded because of recurrent venous thromboembolism within 6 months after the first event. From a societal perspective, for every QALY lost measured with the EQ-5D Dutch tariff, cost savings were euro305.992 (incremental net monetary benefit euro3205, 95% CI 502-5741), and for every QALY lost based on the Short-Form Six-Dimension (SF-6D) utility score (derived from SF-36), cost savings were euro6030.941 (euro3540, 95% CI 1174-5953). Using the UK tariff for EQ-5D, the individualised

We examine the impact of the international diversification of banks on the value of their advice in 1,705 cross-border merger and acquisition (M&A) transactions. We find that bidders engaging internationally diversified advisors face lower announcement returns. An increase of one standard deviation in advisor diversification is associated with an announcement return lower by 92 basis points for a bidder acquiring a listed target. The lower bidder returns are attributable to the lower synergies of the deals being completed. Our evidence suggests that internationally diversified advisors offer lower-quality advice to their clients, since their reputational concerns are weakened by having access to multiple geographies from which they can derive fee-based income. We present further evidence that financial incentives in the form of the advisor’s involvement in deal financing and market incentives in the form of the potential to gain market share in the bidder country may mitigate some of the negative effects of the international diversification of the advisors.

Doen-alsof spel is belangrijk voor de ontwikkeling van kinderen evenals rekenen, schrijven of lezen. Mentale representaties zorgen ervoor dat een kind realiteit en fantasie van elkaar kan onderscheiden, waardoor doen-alsof spel zich kan ontwikkelen. Dit representatieve vermogen hangt samen met de ontwikkeling van een ‘Theory of Mind’. Door middel van mentale staat taal refereren kinderen naar hun mentale en emotionele staat of toestand, onderdeel van een ‘Theory of Mind’. Metacommunicatie, ook wel meta-taal, is taal die gebruikt wordt om het spel zelf te organiseren in tegenstelling tot taal die wordt gebruikt om vanuit de rol te spreken, wat belangrijk is voor de ontwikkeling van het spel. Dit onderzoek heeft gekeken naar de relatie tussen metataal, mentale staat taal en niveau van sociaal doen-alsof spel. Data zijn verkregen op 3 basisscholen onder 35 kleuters van 4.1 tot 5.8 jaar. Kinderen zijn gefilmd tijdens vrij spel op school, dit vond plaats in de eigen klas. De transcripten van deze beelden zijn per uiting geanalyseerd naar het gebruik van metataal en mentale staat taal en het spelniveau . Er is een positieve relatie gevonden tussen meta-taal en niveau van doen-alsof spel. Er is geen relatie gevonden tussen mentale staat taal en niveau van doen-alsof spel. Ook is er geen mediërende of modererende rol van mentale staat taal gevonden. Huidig onderzoek lijkt erop te wijzen dat het gebruik van mentale staat taal als uitdrukking van een ‘Theory of Mind’ geen significante rol speelt in het niveau van sociaal doen-alsof spel. Dit onderzoek geeft nieuwe inzichten voor vervolgonderzoek naar de rol van mentale staat taal binnen meta-taal en doen-alsof spel.

Doen-alsof spel is belangrijk voor de ontwikkeling van kinderen evenals rekenen, schrijven of lezen. Mentale representaties zorgen ervoor dat een kind realiteit en fantasie van elkaar kan onderscheiden, waardoor doen-alsof spel zich kan ontwikkelen. Dit representatieve vermogen hangt samen met de ontwikkeling van een ‘Theory of Mind’. Door middel van mentale staat taal refereren kinderen naar hun mentale en emotionele staat of toestand, onderdeel van een ‘Theory of Mind’. Metacommunicatie, ook wel meta-taal, is taal die gebruikt wordt om het spel zelf te organiseren in tegenstelling tot taal die wordt gebruikt om vanuit de rol te spreken, wat belangrijk is voor de ontwikkeling van het spel. Dit onderzoek heeft gekeken naar de relatie tussen metataal, mentale staat taal en niveau van sociaal doen-alsof spel. Data zijn verkregen op 3 basisscholen onder 35 kleuters van 4.1 tot 5.8 jaar. Kinderen zijn gefilmd tijdens vrij spel op school, dit vond plaats in de eigen klas. De transcripten van deze beelden zijn per uiting geanalyseerd naar het gebruik van metataal en mentale staat taal en het spelniveau . Er is een positieve relatie gevonden tussen meta-taal en niveau van doen-alsof spel. Er is geen relatie gevonden tussen mentale staat taal en niveau van doen-alsof spel. Ook is er geen mediërende of modererende rol van mentale staat taal gevonden. Huidig onderzoek lijkt erop te wijzen dat het gebruik van mentale staat taal als uitdrukking van een ‘Theory of Mind’ geen significante rol speelt in het niveau van sociaal doen-alsof spel. Dit onderzoek geeft nieuwe inzichten voor vervolgonderzoek naar de rol van mentale staat taal binnen meta-taal en doen-alsof spel.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Axonal loss and neuro-inflammation are two early hallmarks of multiple sclerosis (MS), which is a chronic neurodegenerative disease of the central nervous system (CNS). Removing myelin and neuronal debris is a general role for microglia to maintain CNS homeostasis and to promote remyelination. However, during neuro-inflammation in MS two phenotypes of activated macrophages (M1 and M2) are present in active and chronic active MS lesions. They originate from bone marrow or the yolk sac and are named bone marrow-derived macrophages or resident microglia respectively. Several studies suggest a dual role for macrophages in MS, when they are activated they might play a neurotoxic or a neuroprotective role. A phenotypic switch of macrophages induces M1 macrophages in active MS lesions, which leads to an enhanced level of pro-inflammatory cytokines. Macrophages produce neurotrophic factors to communicate with neurons, which is essential to promote neuronal survival. Some of the current therapies for MS are based upon regulation of M1 and M2 macrophages, to reduce neuronal loss. We propose that macrophages play both a harmful and beneficial role in neuroregeneration in which clearance of debris and secretion of macrophage-derived cytokines results in neuronal protection. Conversely, ROS, NO and pro-inflammatory cytokines secreted by M1 macrophages promote neuronal damage. During MS the clearance of debris and the production of cytokines that promote neuronal survival might be inhibited.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Contains fulltext : 135011.pdf (publisher's version ) (Closed access), Visual attention is used to selectively filter relevant information depending on current task demands and goals. Visual attention is called object-based attention when it is directed to coherent forms or objects in the visual field. This study used real-time functional magnetic resonance imaging for moment-to-moment decoding of attention to spatially overlapped objects belonging to two different object categories. First, a whole-brain classifier was trained on pictures of faces and places. Subjects then saw transparently overlapped pictures of a face and a place, and attended to only one of them while ignoring the other. The category of the attended object, face or place, was decoded on a scan-by-scan basis using the previously trained decoder. The decoder performed at 77.6% accuracy indicating that despite competing bottom-up sensory input, object-based visual attention biased neural patterns towards that of the attended object. Furthermore, a comparison between different classification approaches indicated that the representation of faces and places is distributed rather than focal. This implies that real-time decoding of object-based attention requires a multivariate decoding approach that can detect these distributed patterns of cortical activity.

Axonal loss and neuro-inflammation are two early hallmarks of multiple sclerosis (MS), which is a chronic neurodegenerative disease of the central nervous system (CNS). Removing myelin and neuronal debris is a general role for microglia to maintain CNS homeostasis and to promote remyelination. However, during neuro-inflammation in MS two phenotypes of activated macrophages (M1 and M2) are present in active and chronic active MS lesions. They originate from bone marrow or the yolk sac and are named bone marrow-derived macrophages or resident microglia respectively. Several studies suggest a dual role for macrophages in MS, when they are activated they might play a neurotoxic or a neuroprotective role. A phenotypic switch of macrophages induces M1 macrophages in active MS lesions, which leads to an enhanced level of pro-inflammatory cytokines. Macrophages produce neurotrophic factors to communicate with neurons, which is essential to promote neuronal survival. Some of the current therapies for MS are based upon regulation of M1 and M2 macrophages, to reduce neuronal loss. We propose that macrophages play both a harmful and beneficial role in neuroregeneration in which clearance of debris and secretion of macrophage-derived cytokines results in neuronal protection. Conversely, ROS, NO and pro-inflammatory cytokines secreted by M1 macrophages promote neuronal damage. During MS the clearance of debris and the production of cytokines that promote neuronal survival might be inhibited.

Item does not contain fulltext, A brain-computer interface (BCI) enables direct communication from the brain to devices, bypassing the traditional pathway of peripheral nerves and muscles. Traditional approaches to BCIs require the user to train for weeks or even months to learn to control the BCI. In contrast, BCIs based on machine learning only require a calibration session of less than an hour before the system can be used, since the machine adapts to the user's existing brain signals. However, this calibration session has to be repeated before each use of the BCI due to inter-session variability, which makes using a BCI still a time-consuming and an error-prone enterprise. In this work, we present a second-order baselining procedure that reduces these variations, and enables the creation of a BCI that can be applied to new subjects without such a calibration session. The method was validated with a motor-imagery classification task performed by 109 subjects. Results showed that our subject-independent BCI without calibration performs as well as the popular common spatial patterns (CSP)-based BCI that does use a calibration session.

2011 IEEE Symposium on Computational Intelligence, Cognitive Algorithms, Mind, and Brain (CCMB), Paris, 11-15 April 2011, 11 april 2011, Contains fulltext : 92014.pdf (author's version ) (Open Access)

Item does not contain fulltext, Brain-computer interfaces (BCIs) are known to suffer from spontaneous changes in the brain activity. If changes in the mental state of the user are reflected in the brain signals used for control, the behavior of a BCI is directly influenced by these states. We investigate the influence of a state of loss of control in a variant of Pacman on the performance of BCIs based on motor control. To study the effect a temporal loss of control has on the BCI performance, BCI classifiers were trained on electroencephalography (EEG) recorded during the normal control condition, and the classification performance on segments of EEG from the normal and loss of control condition was compared. Classifiers based on event-related desynchronization unexpectedly performed significantly better during the loss of control condition; for the event-related potential classifiers there was no significant difference in performance.

Item does not contain fulltext, A brain-computer interface (BCI) enables direct communication from the brain to devices, bypassing the traditional pathway of peripheral nerves and muscles. Traditional approaches to BCIs require the user to train for weeks or even months to learn to control the BCI. In contrast, BCIs based on machine learning only require a calibration session of less than an hour before the system can be used, since the machine adapts to the user's existing brain signals. However, this calibration session has to be repeated before each use of the BCI due to inter-session variability, which makes using a BCI still a time-consuming and an error-prone enterprise. In this work, we present a second-order baselining procedure that reduces these variations, and enables the creation of a BCI that can be applied to new subjects without such a calibration session. The method was validated with a motor-imagery classification task performed by 109 subjects. Results showed that our subject-independent BCI without calibration performs as well as the popular common spatial patterns (CSP)-based BCI that does use a calibration session.