103 research outputs found
Anaesthesia Monitoring by Recurrence Quantification Analysis of EEG Data
Appropriate monitoring of the depth of anaesthesia is crucial to prevent deleterious effects of insufficient anaesthesia on surgical patients. Since cardiovascular parameters and motor response testing may fail to display awareness during surgery, attempts are made to utilise alterations in brain activity as reliable markers of the anaesthetic state. Here we present a novel, promising approach for anaesthesia monitoring, basing on recurrence quantification analysis (RQA) of EEG recordings. This nonlinear time series analysis technique separates consciousness from unconsciousness during both remifentanil/sevoflurane and remifentanil/propofol anaesthesia with an overall prediction probability of more than 85%, when applied to spontaneous one-channel EEG activity in surgical patients
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Brain network integration dynamics are associated with loss and recovery of consciousness induced by sevoflurane
Funder: Canadian Institute for Advanced Research; Id: http://dx.doi.org/10.13039/100007631Funder: Gates Cambridge Trust; Id: http://dx.doi.org/10.13039/501100005370Funder: Queens College CambridgeFunder: Stephen Erskine FellowshipFunder: Royal College Of Anaesthetists; Id: http://dx.doi.org/10.13039/501100001297Funder: British Oxygen ProfessorshipFunder: Technische UniversitĂ€t MĂŒnchen; Id: http://dx.doi.org/10.13039/501100005713Abstract: The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a subâstate where integration predominates, and a predominantly segregated subâstate, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare restingâstate functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished smallâworld character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burstâsuppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain's default mode and executive control networks dynamically reconfigure depending on the brain's state of integration or segregation. Taken together, our results demonstrate that the integrated subâstate of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery
A mobile detector for measurements of the atmospheric muon flux in underground sites
Muons comprise an important contribution of the natural radiation dose in air
(approx. 30 nSv/h of a total dose rate of 65-130 nSv/h), as well as in
underground sites even when the flux and relative contribution are
significantly reduced. The flux of the muons observed in underground can be
used as an estimator for the depth in mwe (meter water equivalent) of the
underground site. The water equivalent depth is an important information to
devise physics experiments feasible for a specific site. A mobile detector for
performing measurements of the muon's flux was developed in IFIN-HH, Bucharest.
Consisting of 2 scintillator plates (approx. 0.9 m2) which measure in
coincidence, the detector is installed on a van which facilitates measurements
at different locations at surface or underground. The detector was used to
determine muon fluxes at different sites in Romania. In particular, data were
taken and the values of meter water equivalents were assessed for several
locations from the salt mine from Slanic Prahova, Romania. The measurements
have been performed in 2 different galleries of the Slanic mine at different
depths. In order to test the stability of the method, also measure- ments of
the muon flux at surface at different elevations were performed. The results
were compared with predictions of Monte-Carlo simulations using the CORSIKA and
MUSIC codes
Supersymmetry Breaking in Low Dimensional Models
We analyse supersymmetric models that show supersymmetry breaking in one and
two dimensions using lattice methods. Starting from supersymmetric quantum
mechanics we explain the fundamental principles and problems that arise in
putting supersymmetric models onto the lattice. We compare our lattice results
(built upon the non-local SLAC derivative) with numerically exact results
obtained within the Hamiltonian approach. A particular emphasis is put on the
discussion of boundary conditions. We investigate the ground state structure,
mass spectrum, effective potential and Ward identities and conclude that
lattice methods are suitable to derive the physical properties of
supersymmetric quantum mechanics, even with broken supersymmetry. Based on this
result we analyse the two dimensional N=1 Wess-Zumino model with spontaneous
supersymmetry breaking. First we show that (in agreement with earlier
analytical and numerical studies) the SLAC derivative is a sensible choice in
the quenched model, which is nothing but the two dimensional phi^4 model. Then,
we present the very first computation of a renormalised critical coupling for
the complete supersymmetric model. This calculation makes use of Binder
cumulants and is supported by a direct comparison to Ward identity results,
both in the continuum and infinite volume limit. The physical picture is
completed by masses at two selected couplings, one in the supersymmetric phase
and one in the supersymmetry broken phase. Signatures of the Goldstino in the
fermionic correlator are clearly visible in the broken case.Comment: 33 pages, 28 figure
Low Dose Isoflurane Exerts Opposing Effects on Neuronal Network Excitability in Neocortex and Hippocampus
The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity
Fertility education for adolescent cancer patients: Gaps in current clinical practice in Europe
Objective:
As adolescent cancer patients may suffer from infertility following treatment, fertility counselling is essential. Our aim was to explore the current situation in four European countries in terms of (I) education about the risk for infertility, (II) counselling on fertility preservation, (III) patients' knowledge on fertility, (IV) sufficiency of information and (V) uptake of cryopreservation.
Methods:
In total, 113 patients (13â20 years) at 11 study centres completed a self-report questionnaire three and six months after cancer diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI).
Results:
As many as 80.2% of participants reported having received education about the risk for infertility prior to treatment, 73.2% recalled counselling on fertility preservation. Only 52.3% stated they felt sufficiently informed to make a decision. Inability to recall counselling on fertility preservation (OR = 0.03, CI: 0.00â0.47) and female gender (OR = 0.11, CI: 0.03â0.48) was associated with lower use of cryopreservation, whereas older age was associated with higher use.
Conclusion:
Fertility counselling was available to a relatively high proportion of patients, and it did influence the utilisation of cryopreservation. However, many patients did not feel sufficiently informed. Further improvement is needed to enable adolescent cancer patients to make an informed decision on fertility preservation
Infektionsmedizinische und chirurgische Herausforderungen durch Carbapenem-resistente bakterielle Erreger bei der Versorgung Kriegsverletzter aus der Ukraine
Aufgrund von Hygienedefiziten und dem sehr breiten, kalkulierten Antibiotikaeinsatz bei zeitÂŹgleich offener Wundbehandlung in ukrainischen MilitĂ€rkrankenhĂ€usern ist das Risiko fĂŒr schwerwiegende Wundinfektionen mit multiresisÂŹtenten Erregern (MRE) bei Ăbernahme ziviler Kriegsopfer hoch. Insofern kommt der Surveillance mit risikoadaptiertem Screening auf MRE, welches am UniversitĂ€tsklinikum Leipzig seit 2012 durchgefĂŒhrt wird, eine groĂe Bedeutung zu. Es werden die KomplexitĂ€t der Versorgung Kriegsverletzter aus der Ukraine sowie die damit einhergehenden Infektions- und Resistenzprobleme dargestellt und auf die Notwendigkeit eines interdisziplinĂ€ren und -professionellen Managements hingewiesen.Peer Reviewe
Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer.
Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably 'silent' genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or its activating polo-like kinase 1 (PLK1) can be employed to induce fatal genomic instability and tumor regression. We find that the EwS-specific oncogenic transcription factor EWSR1-FLI1 hijacks PRC1, which physiologically safeguards controlled cell division, through binding to a proximal enhancer-like GGAA-microsatellite, thereby promoting tumor growth and poor clinical outcome. Via integration of transcriptome-profiling and functional in vitro and in vivo experiments including CRISPR-mediated enhancer editing, we discover that high PRC1 expression creates a therapeutic vulnerability toward PLK1 inhibition that can repress even chemo-resistant EwS cells by triggering mitotic catastrophe.Collectively, our results exemplify how aberrant PRC1 activation by a dominant oncogene can confer malignancy but provide opportunities for targeted therapy, and identify PRC1 expression as an important determinant to predict the efficacy of PLK1 inhibitors being used in clinical trials.This work was mainly supported by a grant from the German Cancer Aid (DKH-70114111). In addition, the laboratory of T.G.P.G. was supported by the LMU Munichâs Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the âMehr LEBEN fĂŒr krebskranke KinderâBettina-BrĂ€u-Stiftungâ, the Matthias-Lackas Foundation, the Dr. Leopold and Carmen Ellinger Foundation, the Boehringer-Ingelheim Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Barbara and Hubertus Trettner Foundation, the Dr. Rolf M. Schwiete Foundation, the Friedrich-Baur Foundation, the German Cancer Aid (DKH-70112257 and DKH-111886), the Gert und Susanna Mayer Foundation, the Barbara und Wilfried Mohr Foundation, the SMARCB1 association, and the Deutsche Forschungsgemeinschaft (DFG-391665916). J.L. was supported by a scholarship of the Chinese Scholarship Council (CSC), and a grant of the German Cancer Aid (DKH-70114111). M.D. was by a scholarship of the âDeutsche Stiftung fĂŒr junge Erwachsene mit Krebsâ, J.M. by a scholarship of the Kind-Philipp-Foundation, and C.M.F., M.K. and T.L.B.H. by scholarships from the German Cancer Aid. The laboratory of J.A. was supported by grants from the Instituto de Salud Carlos III (PI16CIII/00026; DTS18CIII/00005), AsociaciĂłn Pablo Ugarte, ASION, FundaciĂłn Sonrisa de Alex, AsociaciĂłn Todos somos IvĂĄn y AsociaciĂłn Candela Riera. Freely available clipart used for design of parts of figures was kindly provided by Servier Medical Art (https://smart.servier.com/).S
Gene expression and immunohistochemical analyses identify SOX2 as major risk factor for overall survival and relapse in Ewing sarcoma patients
BACKGROUND: Up to 30-40% of Ewing sarcoma (EwS) patients with non-metastatic disease develop local or metastatic relapse within a time span of 2-10âŻyears. This is in part caused by the absence of prognostic biomarkers that can identify high-risk patients and thus assign them to risk-adapted monitoring and treatment regimens. Since cancer stemness has been associated with tumour relapse and poor patient outcomes, we investigated in the current study the prognostic potential SOX2 (sex determining region Y box 2) - a major transcription factor involved in development and stemness - which was previously described to contribute to the undifferentiated phenotype of EwS. METHODS: Two independent patient cohorts, one consisting of 189 retrospectively collected EwS tumours with corresponding mRNA expression data (test-cohort) and the other consisting of 141 prospectively collected formalin-fixed and paraffin-embedded resected tumours (validation and cohort), were employed to analyse SOX2 expression levels through DNA microarrays or immunohistochemistry, respectively, and to compare them with clinical parameters and patient outcomes. Two methods were employed to test the validity of the results at both the mRNA and protein levels. FINDINGS: Both cohorts showed that only a subset of EwS patients (16-20%) expressed high SOX2 mRNA or protein levels, which significantly correlated with poor overall survival. Multivariate analyses of our validation-cohort revealed that high SOX2 expression represents a major risk-factor for poor survival (HRâŻ=âŻ3·19; 95%CI 1·74-5·84; pâŻ<âŻ0·01) that is independent from metastasis and other known clinical risk-factors at the time of diagnosis. Univariate analyses demonstrated that SOX2-high expression was correlated with tumour relapse (pâŻ=âŻ0·002). The median first relapse was at 14·7âŻmonths (range: 3·5-180·7). INTERPRETATION: High SOX2 expression constitutes an independent prognostic biomarker for EwS patients with poor outcomes. This may help to identify patients with localised disease who are at high risk for tumour relapse within the first two years after diagnosis. FUNDING: The laboratory of T. G. P. GrĂŒnewald is supported by grants from the 'Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen FakultĂ€t der LMU MĂŒnchen (WiFoMed)', by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the 'Mehr LEBEN fĂŒr krebskranke Kinder - Bettina-BrĂ€u-Stiftung', the Walter Schulz Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Friedrich-Baur foundation, the Matthias-Lackas foundation, the Barbara & Hubertus Trettner foundation, the Dr. Leopold & Carmen Ellinger foundation, the Gert & Susanna Mayer foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916), and by the German Cancer Aid (DKH-111886 and DKH-70112257). J. Li was supported by a scholarship of the China Scholarship Council (CSC), J. Musa was supported by a scholarship of the Kind-Philipp foundation, and T. L. B. Hölting by a scholarship of the German Cancer Aid. M. F. Orth and M. M. L. Knott were supported by scholarships of the German National Academic Foundation. G. Sannino was supported by a scholarship from the Fritz-Thyssen Foundation (FTF-40.15.0.030MN). The work of U. Dirksen is supported by grants from the German Cancer Aid (DKH-108128, DKH-70112018, and DKH-70113419), the ERA-Net-TRANSCAN consortium (project number 01KT1310), and Euro Ewing Consortium (EEC, project number EU-FP7 602,856), both funded under the European Commission Seventh Framework Program FP7-HEALTH (http://cordis.europa.eu/), the Barbara & Hubertus Trettner foundation, and the Gert & Susanna Mayer foundation. G. Hardiman was supported by grants from the National Science Foundation (SC EPSCoR) and National Institutes of Health (U01-DA045300). The laboratory of J. Alonso was supported by Instituto de Salud Carlos III (PI12/00816; PI16CIII/00026); AsociaciĂłn Pablo Ugarte (TPY-M 1149/13; TRPV 205/18), ASION (TVP 141/17), FundaciĂłn Sonrisa de Alex & Todos somos IvĂĄn (TVP 1324/15).The laboratory of T. G. P. GrĂŒnewald is supported by grants from the âVerein zur Förderung von Wissenschaft und Forschung an der Medizinischen FakultĂ€t der LMU MĂŒnchen (WiFoMed)â, by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the âMehr LEBEN fĂŒr krebskranke Kinder â Bettina-BrĂ€u-Stiftungâ, the Walter Schulz Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Friedrich-Baur foundation, the Matthias-Lackas foundation, the Barbara & Hubertus Trettner foundation, the Dr. Leopold und Carmen Ellinger foundation, the Gert & Susanna Mayer foundation, the Rolf M. Schwiete foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916), and by the German Cancer Aid (DKH-111886 and DKH-70112257). J. Li was supported by a scholarship of the China Scholarship Council (CSC), J. Musa was supported by a scholarship of the Kind-Philipp foundation, and T. L. B. Hölting by a scholarship of the German Cancer Aid. M. F. Orth and M. M. L. Knott were supported by scholarships of the German National Academic Foundation. G. Sannino was supported from a scholarship from the Fritz-Thyssen Foundation (FTF-40.15.0.030MN). The work of U. Dirksen is supported by grants from the German Cancerr Aid (DKH-108128, DKH-70112018, and DKH-70113419), the ERA-Net-TRANSCAN consortium (project number 01KT1310), and Euro Ewing Consortium (EEC, project number EU-FP7 602856), both funded under the European Commission Seventh Framework Program FP7-HEALTH (http://cordis.europa.eu/), the Barbara & Hubertus Trettner foundation, and the Gert & Susanna Mayer foundation. G. Hardiman was supported by grants from the National Science Foundation (SC EPSCoR) and National Institutes of Health (U01-DA045300). The laboratory of J. Alonso was supported by Instituto de Salud Carlos III (PI12/00816; PI16CIII/00026); AsociaciĂłn Pablo Ugarte (TPY-M 1149/13; TRPV 205/18), ASION (TVP 141/17), FundaciĂłn Sonrisa de Alex & Todos somos IvĂĄn (TVP 1324/15).S
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