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Wägele, Johann Wolfgang ; Letsch, Harald ; Klussmann-Kolb, Annette ; Mayer, Christoph ; Misof, Bernhard ; Wägele, Heike
Background: Molecular phylogenies are being published increasingly and many biologists rely on the most recent topologies. However, different phylogenetic trees often contain conflicting results and contradict significant background data. Not knowing how reliable traditional knowledge is, a crucial question concerns the quality of newly produced molecular data. The information content of DNA alignments is rarely discussed, as quality statements are mostly restricted to the statistical support of clades. Here we present a case study of a recently published mollusk phylogeny that contains surprising groupings, based on five genes and 108 species, and we apply new or rarely used tools for the analysis of the information content of alignments and for the filtering of noise (masking of random-like alignment regions, split decomposition, phylogenetic networks, quartet mapping). Results: The data are very fragmentary and contain contaminations. We show that that signal-like patterns in the data set are conflicting and partly not distinct and that the reported strong support for a "rather surprising result" (monoplacophorans and chitons form a monophylum Serialia) does not exist at the level of primary homologies. Split-decomposition, quartet mapping and neighbornet analyses reveal conflicting nucleotide patterns and lack of distinct phylogenetic signal for the deeper phylogeny of mollusks. Conclusion: Even though currently a majority of molecular phylogenies are being justified with reference to the 'statistical' support of clades in tree topologies, this confidence seems to be unfounded. Contradictions between phylogenies based on different analyses are already a strong indication of unnoticed pitfalls. The use of tree-independent tools for exploratory analyses of data quality are highly recommended. Concerning the new mollusk phylogeny more convincing evidence is needed.
Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis
(2017)
Schmitz, Katja ; Brunkhorst, Robert ; Bruin, Natasja de ; Mayer, Christoph ; Häussler, Annett ; Ferreirós Bouzas, Nerea ; Schiffmann, Susanne ; Parnham, Michael J. ; Tunaru, Sorin ; Chun, Jerold ; Offermanns, Stefan ; Förch, Christian ; Scholich, Klaus ; Vogt, Johannes ; Wicker, Sabine ; Lötsch, Jörn ; Geisslinger, Gerd ; Tegeder, Irmgard
Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2 -/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the ‘symptom-free’ intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.
Mayer, Christoph ; Pfeilschifter, Waltraud ; Lorenz, Matthias ; Nedelmann, Max ; Bechmann, Ingo Jürgen ; Steinmetz, Helmuth ; Ziemann, Ulf
Background: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed ‘chronic cerebrospinal venous insufficiency’ (CCSVI) was proposed, provoking significant attention in the media and scientific community.
Methods: Twenty MS patients (mean age 42.2±13.3 years; median Extended Disability Status Scale 3.0, range 0–6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA≤0.3 cm2 indicated ‘stenosis,’ and IJV-VCSA decrease from supine to upright position ‘reverted postural control.’ The sonographer, data analyser and statistician were blinded to the patient/control status of the participants.
Results: No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA≤0.3 cm2 was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI.
Conclusions: This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.
Blood levels of Glial Fibrillary Acidic Protein (GFAP) in patients with neurological diseases
(2013)
Mayer, Christoph ; Brunkhorst, Robert ; Niessner, Marion ; Pfeilschifter, Waltraud ; Steinmetz, Helmuth ; Förch, Christian
Background and Purpose: The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. Comparably little, however, is known about GFAP release in other neurological disorders. In order to identify potential “specificity gaps” of a future GFAP test used to diagnose intracerebral hemorrhage, we measured GFAP in the blood of a large and rather unselected collective of patients with neurological diseases.
Methods: Within a one-year period, we randomly selected in-patients of our university hospital for study inclusion. Patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage were excluded. Primary endpoint was the ICD-10 coded diagnosis reached at discharge. During hospital stay, blood was collected, and GFAP plasma levels were determined using an advanced prototype immunoassay at Roche Diagnostics.
Results: A total of 331 patients were included, covering a broad spectrum of neurological diseases. GFAP levels were low in the vast majority of patients, with 98.5% of cases lying below the cut-off that was previously defined for the differentiation of intracerebral hemorrhage and ischemic stroke. No diagnosis or group of diagnoses was identified that showed consistently increased GFAP values. No association with age and sex was found.
Conclusion: Most acute and chronic neurological diseases, including typical stroke mimics, are not associated with detectable GFAP levels in the bloodstream. Our findings underline the hypothesis that rapid astroglial destruction as in acute intracerebral hemorrhage is mandatory for GFAP increase. A future GFAP blood test applied to identify patients with intracerebral hemorrhage is likely to have a high specificity.
Coherent photo-production of sons in ultra-peripheral Pb-Pb collisions at the LHC measured by ALICE
(2014)
We present the differential cross section for coherent ρ0 photo-production at mid-rapidity (−0.5 < y < 0.5) measured by the ALICE experiment in Pb-Pb collisions at √sNN = 2.76 TeV at the LHC, as well as the total ρ0 cross section obtained by modelbased extrapolation to all rapidities. These cross sections are compared to various model predictions, as well as to earlier measurements at RHIC. In addition, we present results on nuclear breakup in coincidence with coherent ρ0 photo-production.
Apheresis therapies for NMOSD attacks : a retrospective study of 207 therapeutic interventions
(2018)
Kleiter, Ingo ; Gahlen, Anna ; Borisow, Nadja ; Fischer, Katrin ; Wernecke, Klaus-Dieter ; Hellwig, Kerstin ; Pache, Florence ; Ruprecht, Klemens ; Havla, Joachim ; Kümpfel, Tania ; Aktas, Orhan ; Hartung, Hans-Peter ; Ringelstein, Marius ; Geis, Christian ; Kleinschnitz, Christoph ; Berthele, Achim ; Hemmer, Bernhard ; Angstwurm, Klemens ; Stellmann, Jan-Patrick ; Schuster, Simon ; Stangel, Martin ; Lauda, Florian ; Tumani, Hayrettin ; Mayer, Christoph ; Krumbholz, Markus ; Zeltner, Lena ; Ziemann, Ulf ; Linker, Ralf ; Schwab, Matthias ; Marziniak, Martin ; Then Bergh, Florian ; Hofstadt-van Oy, Ulrich ; Neuhaus, Oliver ; Zettl, Uwe K. ; Faiss, Jürgen Hartmut ; Wildemann, Brigitte ; Paul, Friedemann ; Jarius, Sven ; Trebst, Corinna
Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).
Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody–seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome.
Results: Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04–144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89–0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76–631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03–21.62, p = 0.046).
Conclusions: Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques.
Classification of evidence: This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.
Jarius, Sven ; Ruprecht, Klemens ; Wildemann, Brigitte ; Kümpfel, Tania ; Ringelstein, Marius ; Geis, Christian ; Kleiter, Ingo ; Kleinschnitz, Christoph ; Berthele, Achim ; Brettschneider, Johannes ; Hellwig, Kerstin ; Hemmer, Bernhard ; Linker, Ralf A. ; Lauda, Florian ; Mayer, Christoph ; Tumani, Hayrettin ; Melms, Arthur ; Trebst, Corinna ; Stangel, Martin ; Marziniak, Martin ; Hoffmann, Frank ; Schippling, Sven ; Faiss, Jürgen H. ; Neuhaus, Oliver ; Ettrich, Barbara ; Zentner, Christian ; Guthke, Kersten ; Hofstadt-van Oy, Ulrich ; Reuss, Reinhard ; Pellkofer, Hannah ; Ziemann, Ulf ; Kern, Peter ; Wandinger, Klaus-Peter ; Bergh, Florian T. ; Böttcher, Tobias ; Langel, Stefan ; Liebetrau, Martin ; Rommer, Paulus S. ; Niehaus, Sabine ; Münch, Christoph ; Winkelmann, Alexander ; Zettl, Uwe Klaus ; Metz, Imke ; Veauthier, Christian ; Sieb, Jörn P. ; Wilke, Christian ; Hartung, Hans P. ; Aktas, Orhan ; Paul, Friedemann
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Conclusion: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients
Gracien, René-Maxime ; Jurcoane, Alina ; Wagner, Marlies ; Reitz, Sarah ; Mayer, Christoph ; Volz, Steffen ; Hof, Stephanie-Michelle ; Fleischer, Vinzenz ; Droby, Amgad ; Steinmetz, Helmuth ; Zipp, Frauke ; Hattingen, Elke ; Deichmann, Ralf ; Klein, Johannes Christian
Purpose: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS.
Materials and Methods: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences.
Results: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex.
Conclusion: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.
Cortese, Pietro ; Abelev, Betty ; Adam, Jaroslav ; Adamová, Dagmar ; Adare, A. M. ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agocs, A. G. ; Agostinelli, A. ; Aguilar Salazar, S. ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahmad Masoodi, A. ; Ahn, Sang Un ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Almaraz Avina, E. ; Alme, Johan ; Alt, Torsten ; Altini, V. ; Altinpinar, Sedat ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anielski, Jonas ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, N. ; Arcelli, Silvia ; Arend, A. ; Armesto, Néstor ; Arnaldi, Roberta ; Aronsson, Tomas Robert ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Asryan, A. ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, T. C. ; Aysto, J. ; Azmi, Mohd Danish ; Bach, Matthias ; Badalà, Angela ; Baek, Yong Wook ; Bailhache, Raphaëlle ; Bala, Remu ; Baldini Ferroli, Rinaldo ; Baldisseri, Alberto ; Baldit, A. ; Baltasar Dos Santos Pedrosa, Fernando ; Ban, J. ; Baral, Rama Chandra ; Barbera, Roberto ; Barile, Francesco ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barret, Valerie ; Bartke, Jerzy ; Basile, Maurizio ; Bastid, Nicole ; Basu, Sumit ; Bathen, Bastian ; Batigne, Guillaume ; Batyunya, Boris ; Baumann, C. ; Bearden, Ian Gardner ; Beck, Hans ; Belikov, Iouri ; Bellini, Francesca ; Bellwied, Rene ; Belmont-Moreno, Ernesto ; Bencédi, Gyula ; Beolè, Stefania ; Berceanu, Ionela ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Bhati, Ashok Kumar ; Bhom, Jihyun ; Bianchi, Nicola ; Bianchi, Livio ; Bianchin, Chiara ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Bjelogrlic, Sandro ; Blanco, Fernando ; Blanco, Fernando ; Blau, Dmitry S. ; Blume, Christoph ; Boccioli, M. ; Bock, N. ; Bogdanov, Alexey A. ; Boggild, H. ; Bogolyubsky, M. ; Boldizsar, László ; Bombara, Marek ; Book, Julian ; Borel, Hervé ; Borissov, Alexander ; Bose, S. ; Bossú, Francesco ; Botje, Michiel ; Bottger, Stefan ; Boyer, B. ; Braidot, E. ; Braun-Munzinger, Peter ; Bregant, Marco ; Breitner, Timo ; Browning, Tyler Allen ; Broz, Michal ; Brun, René ; Bruna, Elena ; Bruno, Giuseppe Eugenio ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bugaiev, K. ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Caballero Orduna, D. ; Caffarri, Davide ; Cai, Xiao ; Caines, Helen Louise ; Calvo Villar, Ernesto ; Camerini, Paolo ; Canoa Roman, Veronica ; Cara Romeo, G. ; Carena, Wisla ; Carena, Francesco ; Carlin Filho, N. ; Carminati, F. ; Carrillo Montoya, C. A. ; Casanova Diaz, A. ; Castillo Castellanos, Javier Ernesto ; Castillo Hernández, Juan Francisco ; Casula, E. A.R. ; Catanescu, V. ; Cavicchioli, Costanza ; Ceballos Sanchez, Cesar ; Čepila, Jan ; Cerello, Piergiorgio ; Chang, B. ; Chapeland, Sylvain ; Charvet, Jean-Luc Fernand ; Chattopadhyay, S. ; Chattopadhyay, S. ; Chawla, I. ; Cherney, Michael Gerard ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Chochula, Peter ; Chojnacki, Marek ; Choudhury, Subikash ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Chung, Suh-Urk ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Cleymans, Jean Willy Andre ; Coccetti, F. ; Colamaria, Fabio Filippo ; Colella, Domenico ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Constantin, P. ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Corrales Morales, Yasser ; Cortese, Pietro ; Cortes Maldonado, Ismael ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Cotallo, M. E. ; Crescio, E. ; Crochet, Philippe ; Cruz Alaniz, E. ; Cuautle Flores, Eleazar ; Cunqueiro Mendez, Leticia ; Dainese, Andrea ; Dalsgaard, Hans Hjersing ; Danu, Andrea ; Das, K. ; Das, Indranil ; Das, Debasish ; Dash, Ajay Kumar ; Dash, Sadhana ; De, Sudipan ; De Barros, G. O.V. ; De Caro, Annalisa ; De Cataldo, Giacinto ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; Delagrange, H. ; Del Castillo Sanchez, E. ; Deloff, Andrzej ; Demanov, V. ; De Marco, Nora ; Denes, Ervin Sandor ; De Pasquale, Salvatore ; Deppman, A. ; Erasmo, G. D. ; De Rooij, R. ; Diaz Corchero, Miguel Angel ; Di Bari, Domenico ; Dietel, Thomas ; Di Giglio, C. ; Di Liberto, S. ; Di Mauro, Antonio ; Di Nezza, Pasquale ; Divià, Roberto ; Djuvsland, Øystein ; Dobrin, Alexandru Florin ; Dobrowolski, Tadeusz Antoni ; Dominguez, I. ; Donigus, Benjamin ; Dordic, Olja ; Driga, O. ; Dubey, Anand Kumar ; Ducroux, Laurent ; Dupieux, Pascal ; Dutta Majumdar, A. K. ; Dutta Majumdar, M. R. ; Elia, Domenico ; Emschermann, D. ; Engel, Heiko ; Erdal, H. A. ; Espagnon, Bruno ; Estienne, Magali Danielle ; Esumi, ShinIchi ; Evans, David ; Eyyubova, Gyulnara ; Fabris, Daniela ; Faivre, Julien ; Falchieri, D. ; Fantoni, Alessandra ; Fasel, Markus ; Fearick, R. ; Fedunov, A. ; Fehlker, D. ; Feldkamp, Linus ; Felea, Daniel ; Fenton-Olsen, B. ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferretti, Alessandro ; Ferretti, R. ; Figiel, Jan ; Figueredo, M. A.S. ; Filchagin, Sergey ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fiore, Enrichetta Maria ; Floris, Michele ; Foertsch, Siegfried Valentin ; Foka, Panagiota ; Fokin, Sergey ; Fragiacomo, Enrico ; Fragkiadakis, M. ; Frankenfeld, Ulrich ; Fuchs, Ulrich ; Furget, Christophe ; Fusco Girard, Mario ; Gaardhoje, J. J. ; Gagliardi, Martino ; Gago, A. ; Gallio, Mauro ; Gangadharan, Dhevan Raja ; Ganoti, Paraskevi ; Garabatos, Chilo ; Garcia-Solis, Edmundo Javier ; Garishvili, I. ; Gerhard, J. ; Germain, Marie ; Geuna, C. ; Gheata, Mihaela ; Gheata, Andrei George ; Ghidini, B. ; Ghosh, Premomoy ; Gianotti, Paola ; Girard, M. R. ; Giubellino, Paolo ; Gładysz-Dziaduś, Ewa ; Glässel, Peter ; Gomez, R. ; Gonzalez Ferreiro, Elena ; González Trueba, Laura Helena ; González Zamora, Pedro ; Gorbunov, Sergey ; Goswami, A. ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Grajcarek, R. ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoras, Alina Gabriela ; Grigoriev, Vladislav A. ; Grigoryan, Smbat ; Grigoryan, Ara ; Grinyov, Boris V. ; Grion, Nevio ; Gros, P. ; Große-Oetringhaus, Jan Fiete ; Grossiord, Grossiord Jean-Yves ; Grosso, Raffaele ; Guber, Fedor ; Guernane, Rachid ; Guerra Gutierrez, C. ; Guerzoni, Barbara ; Guilbaud, Maxime Rene Joseph ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Gupta, Ramni ; Gupta, Anik ; Gutbrod, H. ; Haaland, Øystein Senneset ; Hadjidakis, Cynthia Marie ; Haiduc, Maria ; Hamagaki, Hideki ; Hamar, Gergö ; Han, B. H. ; Hanratty, Luke David ; Hansen, Alexander ; Harmanova, Z. ; Harris, John W. ; Hartig, M. ; Hasegan, D. ; Hatzifotiadou, Despina ; Hayrapetyan, A. ; Heckel, Stefan Thomas ; Heide, Markus ; Helstrup, Håvard ; Herghelegiu, Andrei Ionut ; Herrera Corral, Gerardo Antonio ; Herrmann, Norbert ; Hetland, Kristin Fanebust ; Hicks, B. ; Hille, P. T. ; Hippolyte, Boris ; Horaguchi, T. ; Hori, Y. ; Hristov, Peter ; Hřivnačova, I. ; Huang, M. ; Humanic, Thomas J. ; Hwang, Dae Sung ; Ichou, R. ; Ilkaev, Radiy ; Ilkiv, Iryna ; Inaba, Motoi ; Incani, E. ; Innocenti, P. G. ; Innocenti, G. M. ; Ippolitov, Mikhail ; Irfan, M. ; Ivan, C. ; Ivanov, V. ; Ivanov, A. ; Ivanov, Marian ; Ivanytskyi, O. ; Jacholkowski, Adam Wlodzimierz ; Jacobs, Peter Martin ; Jancurova, L. ; Jang, Haeng Jin ; Jangal, S. ; Janik, R. ; Janik, Malgorzata Anna ; Jayarathna, P. H.S.Y. ; Jena, Satyajit ; Jha, D. M. ; Jiménez Bustamante, Raúl Tonatiuh ; Jirden, L. ; Jones, Peter Graham ; Jung, H. ; Jusko, Anton ; Kaidalov, A. B. ; Kakoyan, V. ; Kalcher, S. ; Kaliňak, Peter ; Kalisky, M. ; Kalliokoski, T. ; Kalweit, Alexander Philipp ; Kanaki, K. ; Kang, Ju Hwan ; Kaplin, Vladimir ; Karasu Uysal, Ayben ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karpechev, Evgeny ; Kazantsev, Andrey ; Kebschull, Udo ; Keidel, Ralf ; Khan, M. M. ; Khan, Shuaib Ahmad ; Khanzadeev, Alexei ; Kharlov, Yury ; Kileng, Bjarte ; Kim, J. S. ; Kim, D. W. ; Kim, S. H. ; Kim, J. H. ; Kim, M. ; Kim, D. J. ; Kim, B. ; Kim, T. ; Kim, S. ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Klay, Jennifer Lynn ; Klein, Jochen ; Klein-Bösing, Christian ; Kliemant, Michael ; Kluge, Alexander ; Knichel, Michael Linus ; Knospe, Anders Garritt ; Koch, K. ; Köhler, Markus Konrad ; Kolojvari, Anatoly ; Kondratiev, Valery P. ; Kondratyeva, Natalia ; Konevskikh, Artem ; Korneev, A. ; Kour, R. ; Kowalski, Marek ; Kox, Serge ; Koyithatta Meethaleveedu, Greeshma ; Kral, Jiří ; Králik, Ivan ; Kramer, F. ; Kraus, Ingrid ; Krawutschke, T. ; Křelina, Michal ; Kretz, Matthias ; Krivda, Marian ; Krizek, Filip ; Krus, M. ; Kryshen, Evgeny ; Krzewicki, Mikolaj ; Kucheriaev, Yury ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kushpil, V. ; Kushpil, Svetlana ; Kvaerno, H. ; Kweon, Min Jung ; Kwon, Youngil ; Ladron de Guevara, Pedro ; Lakomov, Igor ; Langoy, Rune ; La Pointe, Sarah Louise ; Lara Martinez, Camilo Ernesto ; Lardeux, Antoine Xavier ; La Rocca, Paola ; Lazzeroni, C. ; Lea, Ramona ; Le Bornec, Y. ; Lechman, M. ; Lee, S. C. ; Lee, K. S. ; Lefevre, F. ; Lehnert, Jörg ; Leistam, L. ; Lenhardt, M. ; Lenti, Vito ; Leon, H. ; Leon Monzon, Ildefonso ; Leon Vargas, H. ; Lévai, Péter ; Lien, Jørgen André ; Lietava, Roman ; Lindal, Svein ; Lindenstruth, Volker ; Lippmann, Christian ; Lisa, Michael A. ; Liu, L. ; Lønne, Per-Ivar ; Loggins, Vera Renee ; Loginov, Vitaly ; Lohn, S. ; Lohner, D. ; Loizides, Constantinos ; Loo, K. K. ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lovhoiden, G. ; Lu, X. G. ; Lüttig, Philipp ; Lunardon, Marcello ; Luo, J. ; Luparello, Grazia ; Luquin, L. ; Luzzi, C. ; Ma, R. ; Ma, K. ; Madagodahettige-Don, D. 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The ALICE Zero Degree Calorimeter system (ZDC) is composed of two identical sets of calorimeters, placed at opposite sides with respect to the interaction point, 114 meters away from it, complemented by two small forward electromagnetic calorimeters (ZEM). Each set of detectors consists of a neutron (ZN) and a proton (ZP) ZDC. They are placed at zero degrees with respect to the LHC axis and allow to detect particles emitted close to beam direction, in particular neutrons and protons emerging from hadronic heavy-ion collisions (spectator nucleons) and those emitted from electromagnetic processes. For neutrons emitted by these two processes, the ZN calorimeters have nearly 100% acceptance.
During the √sNN = 2.76 TeV Pb-Pb data-taking, the ALICE Collaboration studied forward neutron emission with a dedicated trigger, requiring a minimum energy deposition in at least one of the two ZN. By exploiting also the information of the two ZEM calorimeters it has been possible to separate the contributions of electromagnetic and hadronic processes and to study single neutron vs. multiple neutron emission.
The measured cross sections of single and mutual electromagnetic dissociation of Pb nuclei at √sNN = 2.76 TeV, with neutron emission, are σsingle EMD = 187:4 ± 0.2 (stat.)−11.2+13.2 (syst.) b and σmutual EMD = 5.7 ± 0.1 (stat.) ±0.4 (syst.) b, respectively [1]. This is the first measurement of electromagnetic dissociation of 208Pb nuclei at the LHC energies, allowing a test of electromagnetic dissociation theory in a new energy regime. The experimental results are compared to the predictions from a relativistic electromagnetic dissociation model.
Büttner, Stefan ; Stadler, Andrea ; Mayer, Christoph ; Patyna, Sammy ; Betz, Christoph ; Senft, Christian ; Geiger, Helmut ; Jung, Oliver ; Finkelmeier, Fabian
Purpose: Acute kidney injury (AKI) is a severe complication in medical and surgical intensive care units accounting for a high morbidity and mortality. Incidence, risk factors, and prognostic impact of this deleterious condition are well established in this setting. Data concerning the neurocritically ill patients is scarce. Therefore, aim of this study was to determine the incidence of AKI and elucidate risk factors in this special population.
Methods: Patients admitted to a specialized neurocritical care unit between 2005 and 2011 with a length of stay above 48 hours were analyzed retrospectively for incidence, cause, and outcome of AKI (AKI Network-stage ≥2).
Results: The study population comprised 681 neurocritically ill patients from a mixed neurosurgical and neurological intensive care unit. The prevalence of chronic kidney disease (CKD) was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50% of patients. Acute kidney injury and renal replacement therapy are independent predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI: 5.944-26.172; P < .001), whereas surgical intervention or contrast agents were not associated with AKI.
Conclusions: Acute kidney injury in neurocritical care has a high incidence and is a crucial risk factor for mortality independently of the underlying neurocritical condition. Sepsis is the main cause of AKI in this setting. Therefore, careful prevention of infectious complications and considering CKD in treatment decisions may lower the incidence of AKI and hereby improve outcome in neurocritical care.