Belgian Federal Science Policy Office Research Articles

Most of Clinically Unresponsive Patients Present Richer Brain Activity than Expected: Lessons from a Multimodal Neuroimaging Study

Background: A significant proportion of brain-injured patients who are unresponsive at the bedside (i.e., unresponsive wakefulness syndrome – UWS) may present brain activity similar to patients in minimally conscious state (MCS). This peculiar condition has been termed “non-behavioural MCS” or “MCS*”. Methods: Brain 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was acquired on 135 brain-injured patients diagnosed in prolonged UWS (n=48) or MCS (n=87). Clinical diagnosis was based on repeated Coma Recovery Scale-Revised assessments. Relative metabolic preservation in the fronto-parietal network (measured with standardized uptake value) was evaluated by 3 experts blinded to the clinical diagnosis. Patients with hypometabolism of the fronto-parietal network were labelled UWS, while preservation either confirmed the behavioural diagnosis of MCS or, in absence of behavioural signs of consciousness, suggested a diagnosis of MCS*. The clinical outcome at 1-year follow-up, the functional connectivity (measured with electroencephalography), the grey matter atrophy (assessed with magnetic resonance imaging), and the regional brain metabolic patterns were investigated in the three groups (UWS, MCS* and MCS). Findings: Out of the 48 behavioural UWS patients, 32 (67%) presented a partial preservation of brain metabolism (i.e., MCS*). Compared to the hypometabolic UWS patients, MCS* patients demonstrated a better outcome, higher global functional connectivity in the alpha and theta bands, as well as greater grey matter preservation in the frontal and temporal regions, the fusiform gyrus, and the insula. MCS* patients presented lower brain metabolism mostly in the posterior regions compared to MCS patients. Interpretation: MCS* is a frequent phenomenon that is also associated with a better outcome than the diagnosis of UWS. Complementary exams should be provided to all unresponsive patients before taking medical decisions. Funding Statement: Belgian National Funds for Scientific Research, Human Brain Project SGA3 (No. 945539), DOCMA project (EU-H2020-MSCA–RISE–778234), Belgian Federal Science Policy Office (PRODEX), Bial Foundation, fund Generet, King Baudouin Foundation, AstraZeneca Foundation. Declaration of Interests: The authors declare that there is no conflict of interest regarding the publication of this paper. Ethics Approval Statement: The study was approved by the Ethics Committee of the Faculty of Medicine of the University of Liege. Written informed consent was obtained from healthy controls and patients' legal representatives.

Overview of the BINA Activities

Here, we summarize the ongoing activities of an international bilateral research project entitled “Belgo-Indian Network for Astronomy and astrophysics (BINA)” running jointly since 2014 by the astronomers of various Indian and Belgian institutions. The network activities are being financially supported by the Depart-ment of Science and Technology (DST; Government of India) and the Belgian Federal Science Policy Office (BELSPO; Government of Belgium). The structure and mandate of the BINA network are presented. The observational facilities being used to achieve the goals of the project are delineated. The overview of the activities and future perspective in the light of upcoming observational facilities are also highlighted.

Genetic Creutzfeldt-Jakob disease mimicking chronic inflammatory demyelinating polyneuropathy

Creutzfeldt-Jakob disease (CJD) is a relentlessly progressive neurodegenerative disorder, belonging to the transmissible spongiform encephalopathies. It is characterized by the deposition of the abnormal isoform of the prion protein (PrPsc), causing spongiform neurodegeneration. The disease is classically known to mainly affect the gray matter of the CNS. However, involvement of the peripheral nervous system (PNS) has been described.1–3 Herein, we describe a patient with genetic CJD, in whom the disease presentation was a demyelinating neuropathy reminiscent of chronic inflammatory demyelinating polyneuropathy (CIDP). Acknowledgment: This study is supported by a grant from the KU Leuven (GOA/11/014) and by the Interuniversity Attraction Poles (IUAP) program P7/16 of the Belgian Federal Science Policy Office. P.V.D. holds a senior clinical investigatorship from the Flemish Fund for Scientific Research (FWO-Vlaanderen) and is supported by the Belgian ALS league.

The Silk Roads Cultural Heritage Resource Information System: For World Heritage Monitoring and Preservation

Serial transnational World Heritage nominations are challenging the way cultural heritage has been managed and evaluated in the past. This type of nomination requires different methodologies and tools to improve the monitoring cycle from the beginning of the nomination towards the periodic reporting. The case study of the Silk Roads Cultural Heritage Resource Information System (CHRIS) illustrates the use of a Geospatial Content Management System (Geo-CMS) supporting the serial transnational World Heritage nominations and the future monitoring of the Silk Roads in Central Asia. The Silk Roads CHRIS is an initiative supported by UNESCO WHC and the Belgian Federal Science Policy Office (BELSPO), and developed by a consortium headed by the Raymond Lemaire International Centre for Conservation, KULeuven. The Silk Roads CHRIS has been successfully assisting in the preparation of the nomination dossiers of the Republics of Kazakhstan, Tajikistan and Uzbekistan and will be used as a monitoring tool in the Central Asian countries. This paper discusses the use of the system in serial transnational nomination, and describes the architecture of the system, its main features, its effectiveness in the preparation of the nomination dossier and its use during monitoring and reporting.

External validation of models and simple scoring systems to predict miscarriage in intrauterine pregnancies of uncertain viability

Does a logistic regression model and scoring system to predict viability of an intrauterine pregnancy of uncertain viability (PUV) perform as well in an independent patient group as the original patient group? The model and scoring system showed good performance on external validation confirming their value for the prediction of miscarriage/viability in PUV patients up to 11-14 weeks of gestation. Several individual ultrasound and demographic factors have been described as predictors for miscarriage. A logistic regression model and simple scoring system using basic clinical and ultrasound features, such as maternal age, bleeding score, mean gestational sac diameter (MSD) and presence or absence of yolk sac, have been developed to allow patient-specific prediction of viability of PUV beyond the first trimester. Prospective observational external validation cohort study in two inner city early pregnancy assessment units over a period of 18 months. All consecutive women with a PUV were recruited. Ultrasound (mean sac diameter and presence of yolk sac) and demographic variables (maternal age, bleeding score and gestational age) were noted. The outcome measure was first trimester (11-14 week) viability. Women with unknown first trimester outcome were excluded. Receiver operating characteristic (ROC) curves and calibration plots were constructed. Test performance was compared with the original development data set. A new model and scoring system, which did not include gestational age, was built and evaluated. Of the 575 women who were recruited, first trimester outcome was known for 89.2% (n = 513). The model could only be validated in 400 patients, due to missing values in model variables and outcome. The model predicted viability with an area under the ROC curve (AUC) of 0.845 [95% confidence interval (CI), 0.806-0.884] compared with 0.774 (95% CI, 0.701-0.848) in the original study. The AUC for the scoring system was 0.832 (95% CI, 0.792-0.872) compared with 0.771 (95% CI, 0.698-0.844) from the original study data set. The new model and the scoring system, excluding gestational age, could be evaluated on 503 patients and resulted in an AUC of 0.801 (95% CI, 0.765-0.841) for the model and 0.773 (95% CI, 0.733-0.812) for the scoring system. Approximately 22% of patients could not be validated due to missing variables and for 11% of patients the first trimester outcome was unknown. Both the model and the scoring system showed excellent performance on external validation confirming their generalizability and utility in prediction of viability beyond the first trimester in clinical practice. An advantage of the mathematical models original Mo and new Mn and scoring systems original SSo and new SSn is that they can provide women with an individualized probability of the viability of their pregnancy using only demographic information, symptoms and TVS findings. Furthermore, the risk of miscarriage can be given immediately following examination. T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. This research is supported by Research Council KUL GOA MaNet, iMinds 2012, Belgian Federal Science Policy Office IUAP P719. VVB is a postdoctoral fellow of the Research Foundation - Flanders (FWO). There are no conflicts of interest.

CONNECTING WORLD HERITAGE NOMINATIONS AND MONITORING WITH THE SUPPORT OF THE SILK ROADS CULTURAL HERITAGE RESOURCE INFORMATION SYSTEM

Abstract. Serial transnational World Heritage nominations are challenging the way cultural heritage has been managed and evaluated in the past. Serial transnational World Heritage nominations are unique in that they consist of multiple sites listed as one property, distributed in different countries, involving a large diversity of stakeholders in the process. As a result, there is a need for precise baseline information for monitoring, reporting and decision making. This type of nomination requires different methodologies and tools to improve the monitoring cycle from the beginning of the nomination towards the periodic reporting. The case study of the Silk Roads Cultural Heritage Resource Information System (CHRIS) illustrates the use of a Geographical Content Management System (Geo-CMS) supporting the serial transnational World Heritage nomination and the monitoring of the Silk Roads in the five Central Asian countries. The Silk Roads CHRIS is an initiative supported by UNESCO World Heritage Centre (WHC) and the Belgian Federal Science Policy Office (BELSPO), and developed by a consortium headed by the Raymond Lemaire International Centre for Conservation (RLICC) at the KULeuven. The Silk Roads CHRIS has been successfully assisting in the preparation of the nomination dossiers of the Republics of Kazakhstan, Tajikistan and Uzbekistan and will be used as a tool for monitoring tool in the Central Asian countries.

A Miocene relative of the Ganges River dolphin (Odontoceti, Platanistidae) from the Amazonian Basin

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTS P. Loubry (MNHN) took the photographs. We are much indebted to P. Baby, M. Benammi, S. Brusset, D. De Franceschi, and N. Espurt for their participation in field work. This research project was undertaken thanks to the IRD-Perupetro S.A. research agreement, and supported by IRD (UR 154), Devanlay Peru S.A., and the French INSU-CNRS programs DyETI and ECLIPSE II, headed by P. Baby and P.-O. Antoine, respectively. Constructive comments of E. Fitzgerald, an anonymous reviewer, and the editor J. Geisler considerably improved a previous version of this paper. The work of O. Lambert at the IRSNB is funded by a Return Grant of the Belgian Federal Science Policy Office. Handling editor: Jonathan Geisler.

Rationalizing the management of pregnancies of unknown location: temporal and external validation of a risk prediction model on 1962 pregnancies

Can we accurately define a group of pregnancies of unknown location (PULs) as low risk in order to safely reduce follow-up for these pregnancies and allocate resources to pregnancies at an increased risk of being ectopic? Prediction model M4 classified around 70% of PULs as low risk, of which around 97% were later characterized as failed PULs or intrauterine pregnancies (IUPs), while still classifying 88% of ectopic pregnancies as high risk. Depending on the level of suspicion of ectopic pregnancy (EP), women with a PUL receive a lengthy follow-up in order to confirm the location and viability of the pregnancy. A multi-centre diagnostic accuracy study of 1962 patients was carried out between 2003 and 2007 for retrospective temporal validation and between 2009 and 2011 for prospective external validation. The reference standard is the final characterization of PUL as failed pregnancies or IUPs (low risk), or as ectopic pregnancies (high risk). M4 is a multinomial logistic regression model based on the serum human chorionic gonadotrophin (hCG) levels at presentation and 48 h later. Temporal validation data from 1341 PULs collected at St George's Hospital in London were available, of which 53% were failed, 39% were intrauterine and 8% were ectopic pregnancies. External validation data from 621 PULs collected at four other London-based teaching hospitals were available, of which 63% were failed, 22% were intrauterine and 15% were ectopic pregnancies. The EP rate varied between 8 and 16% across the five hospitals. At St George's, 980 [73.1%, 95% confidence interval (CI): 70.5-75.4] PULs were considered low risk. Of these, 963 were failed PULs or IUPs (98.3%, 95% CI: 97.2-98.9) and 17 were ectopic pregnancies. At the other four hospitals, 62-75% were considered low risk, with 96-98% of these turning out to be failed PUL or IUP. Eighty-five percent (95% CI: 76.8-90.2) of the ectopic pregnancies were considered high risk at St George's, compared with 80-92% in the other hospitals. Of total, 120 patients had been excluded due to loss to follow-up, and a further 102 patients because of missing hCG levels due to differences in local clinical practice. There are variations in the definition of a PUL used in different countries. The suggested protocol could safely reduce the follow-up in the majority of PUL such that units could increase the focus on women at a risk of complications. This would lead to a change in the management of the majority of women with a PUL and a more efficient use of resources. At the end of the manuscript, we provide a link to enable clinicians to use the protocol. B.V.C. is supported by a postdoctoral fellowship from the Research Foundation Flanders (FWO). K.V.H. is supported by a fellowship from the Flanders' Agency for Innovation by Science and Technology (IWT-Vlaanderen), by the Research Council KU Leuven (GOA MaNet), by the Flemish Government (iMinds) and by the Belgian Federal Science Policy Office (IUAP P7/DYSCO). T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. No competing interests are declared.

Accurate prediction of pregnancy viability by means of a simple scoring system

What is the performance of a simple scoring system to predict whether women will have an ongoing viable intrauterine pregnancy beyond the first trimester? A simple scoring system using demographic and initial ultrasound variables accurately predicts pregnancy viability beyond the first trimester with an area under the curve (AUC) in a receiver operating characteristic curve of 0.924 [95% confidence interval (CI) 0.900-0.947] on an independent test set. Individual demographic and ultrasound factors, such as maternal age, vaginal bleeding and gestational sac size, are strong predictors of miscarriage. Previous mathematical models have combined individual risk factors with reasonable performance. A simple scoring system derived from a mathematical model that can be easily implemented in clinical practice has not previously been described for the prediction of ongoing viability. This was a prospective observational study in a single early pregnancy assessment centre during a 9-month period. A cohort of 1881 consecutive women undergoing transvaginal ultrasound scan at a gestational age <84 days were included. Women were excluded if the first trimester outcome was not known. Demographic features, symptoms and ultrasound variables were tested for their influence on ongoing viability. Logistic regression was used to determine the influence on first trimester viability from demographics and symptoms alone, ultrasound findings alone and then from all the variables combined. Each model was developed on a training data set, and a simple scoring system was derived from this. This scoring system was tested on an independent test data set. The final outcome based on a total of 1435 participants was an ongoing viable pregnancy in 885 (61.7%) and early pregnancy loss in 550 (38.3%) women. The scoring system using significant demographic variables alone (maternal age and amount of bleeding) to predict ongoing viability gave an AUC of 0.724 (95% CI = 0.692-0.756) in the training set and 0.729 (95% CI = 0.684-0.774) in the test set. The scoring system using significant ultrasound variables alone (mean gestation sac diameter, mean yolk sac diameter and the presence of fetal heart beat) gave an AUC of 0.873 (95% CI = 0.850-0.897) and 0.900 (95% CI = 0.871-0.928) in the training and the test sets, respectively. The final scoring system using demographic and ultrasound variables together gave an AUC of 0.901 (95% CI = 0.881-0.920) and 0.924 (CI = 0.900-0.947) in the training and the test sets, respectively. After defining the cut-off at which the sensitivity is 0.90 on the training set, this model performed with a sensitivity of 0.92, specificity of 0.73, positive predictive value of 84.7% and negative predictive value of 85.4% in the test set. BMI and smoking variables were a potential omission in the data collection and might further improve the model performance if included. A further limitation is the absence of information on either bleeding or pain in 18% of women. Caution should be exercised before implementation of this scoring system prior to further external validation studies This simple scoring system incorporates readily available data that are routinely collected in clinical practice and does not rely on complex data entry. As such it could, unlike most mathematical models, be easily incorporated into normal early pregnancy care, where women may appreciate an individualized calculation of the likelihood of ongoing pregnancy viability. Research by V.V.B. supported by Research Council KUL: GOA MaNet, PFV/10/002 (OPTEC), several PhD/postdoc & fellow grants; IWT: TBM070706-IOTA3, PhD Grants; IBBT; Belgian Federal Science Policy Office: IUAP P7/(DYSCO, `Dynamical systems, control and optimization', 2012-2017). T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. Not applicable.

INFORMATION MANAGEMENT SYSTEMS FOR MONITORING AND DOCUMENTING WORLD HERITAGE - THE SILK ROADS CHRIS

Abstract. This paper discusses the application of Information Management Systems (IMS) for documenting and monitoring World Heritage (WH) properties. The application of IMS in WH can support all stakeholders involved in conservation, and management of cultural heritage by more easily inventorying, mining and exchanging information from multiple sources based on international standards. Moreover, IMS could assist in detecting damages and preparing management strategies to mitigate risks, and slowing down the deterioration of the integrity of WH properties. The case study of the Silk Roads Cultural Heritage Resource Information System (CHRIS), a Belgian Federal Science Policy Office funded project, illustrates the capabilities of IMS in the context of the nomination of the Central Asian Silk Roads on the WH List. This multi-lingual, web-based IMS will act as a collaborative platform allowing for the completion of improved transnational nomination dossiers and subsequent monitoring activities with all necessary baseline information to easily verify consistency and quality of the proposal. The Silk Roads CHRIS Geospatial Content Management System uses open source technologies and allows to georeference data from different scales and sources including data from field recording methods and combine it with historical and heritage features documented through various means such as textual descriptions, documents, photographs, 3D models or videos. Moreover, tailored maps can also be generated by overlaying a selection of available layers and then be exported to support the nomination dossier. Finally, by using this innovative information and decision support system, the State Parties and other interested stakeholders will have access to a complete nomination dossier and could therefore respond more effectively to hazards and disaster phenomena.

Information Management Systems for Cultural Heritage and Conservation of World Heritage Sites. The Silk Roads Case Study

This paper discusses the application of Information Management Systems (IMS) in cultural heritage. IMS offer a set of tools for understanding, inventorying and documenting national, regional and World Heritage properties. Information Management Systems can assist State Parties, stakeholders and heritage site managers involved in cultural heritage management and conservation by easily mining, sharing and exchanging information from multiple sources based on international standards. Moreover, they aim to record, manage, visualize, analyze and disseminate heritage information. In close collaboration with five Central Asian countries, namely, Turkmenistan, Kazakhstan, Kyrgyzstan, Uzbekistan and Tajikistan; a Belgian consortium headed by the Raymond Lemaire International Centre for Conservation (RLICC), K.U.Leuven is developing the Silk Roads Cultural Heritage Resource Information System (CHRIS). This Web-based Information Management System supports the preparation of the Central Asia Silk Roads serial and transnational nominations on the UNESCO World Heritage list. The project has been set up thanks to the financial support of the Belgian Federal Science Policy Office (BELSPO) and in collaboration with UNESCO World Heritage Centre in conjunction with the People’s Republic of China and the Japanese Funds-in-Trust UNESCO project. It provides a holistic approach for the recording, documenta tion, protection and monitoring tasks as part of the management of these potential World Heritage Properties. The Silk Roads CHRIS is easily accessible to the general user, presented in a bilingual English and Russian frame and interoperable, i.e. open for other applications to connect to. In this way, all information for the nomination dossiers is easily verified regarding consistency and quality and ready for managing, periodic reporting and monitoring processes in the respect to the property listed. Fina lly, this study provides a general framework to establish the effectiveness and limits of the use of information systems for serial transnational nominations of World Heritage Properties and to demonstrate the potentials of an improved heritage documentation system.

Gap-singular systems: definition and consequences in trajectory planning†

This article introduces the concept of gap-singularities to underline particular phenomena related to the choice of the outputs in some non-linear systems. It is shown that, when bounds on the variables are considered, this property induces a topological isolation of the gap-singular trajectories in the outputs domain. In the context of differentially flat systems, a procedure to detect gap-singularities is provided because it is related to the existence of a singularity of flatness. The examples that are presented in this article show that taking gap-singularities into account can improve some trajectory planning algorithms based on an optimal control approach like in the Nonlinear Trajectory Generation software. †This article presents research results of the Belgian Programme on Interuniversity Attraction Poles, initiated by the Belgian Federal Science Policy Office. The scientific responsibility rests with its authors.

Quantitative cerebral blood flow determination

<h3>Abstract</h3> In recent years, specific cortical networks have been proposed to be crucial for sustaining consciousness, including the posterior hot zone and frontoparietal resting state networks (RSN). Here, we computationally evaluate the relative contributions of three RSNs – the default mode network (DMN), the salience network (SAL), and the central executive network (CEN) – to consciousness and its loss during propofol anaesthesia. Specifically, we use dynamic causal modelling (DCM) of 10 minutes of high-density EEG recordings (<i>N</i> = 10, 4 males) obtained during behavioural responsiveness, unconsciousness and post-anaesthetic recovery to characterise differences in effective connectivity within frontal areas, the posterior “hot zone”, frontoparietal connections, and between-RSN connections. We estimate – for the first time – a large DCM model (LAR) of resting EEG, combining the three RSNs into a rich club of interconnectivity. Consistent with the hot zone theory, our findings demonstrate reductions in inter-RSN connectivity in the parietal cortex. Within the DMN itself, the strongest reductions are in feed-forward frontoparietal and parietal connections at the precuneus node. Within the SAL and CEN, loss of consciousness generates small increases in bidirectional connectivity. Using novel DCM leave-one-out cross-validation, we show that the most consistent out-of-sample predictions of the state of consciousness come from a key set of frontoparietal connections. This finding also generalises to unseen data collected during post-anaesthetic recovery. Our findings provide new, computational evidence for the importance of the posterior hot zone in explaining the loss of consciousness, highlighting also the distinct role of frontoparietal connectivity in underpinning conscious responsiveness, and consequently, suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness. <h3>Highlights</h3> Modelling shows that connectivity within hot zone tracks change of conscious state Separately, frontoparietal connections support maintenance of conscious state Strength of frontoparietal connections predicts conscious state in unseen data Both parietal hot zone and frontoparietal connectivity important for consciousness <h3>Funding</h3> This work was supported by the UK Engineering and Physical Sciences Research Council (EP/P033199/1), Belgian National Funds for Scientific Research (FRS-FNRS), the University and University Hospital of Liege, the Fund Generet, the King Baudouin Foundation, the AstraZeneca Foundation, the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), DOCMA project (EU-H2020-MSCA–RISE–778234), the BIAL Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Center-TBI project (FP7-HEALTH-602150), the Public Utility Foundation ‘Université Européenne du Travail’, “Fondazione Europea di Ricerca Biomedica”, the Mind Science Foundation, the European Commission, and the Special Research Fund of Ghent University. O.G. is research associate and S.L. is research director at the F.R.S-FNRS. <h3>Declaration of interest</h3> None. <h3>Significance Statement</h3> Various connectivity studies have suggested multiple network-level mechanisms driving changes in the state of consciousness, such as the posterior hot zone, frontal-, and large-scale frontoparietal networks. Here, we computationally evaluate evidence for these mechanisms using dynamic causal modeling for resting EEG recorded before and during propofol-anaesthesia, and demonstrate that, particularly, connectivity in the posterior hot zone is impaired during propofol-induced unconsciousness. With a robust cross-validation paradigm, we show that connectivity in the large-scale frontoparietal networks can consistently predict the state of consciousness and further generalise these findings to an unseen state of recovery. These results suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.