Search

Your search keyword '"Peter Konrad"' showing total 134 results
Start Over Author "Peter Konrad"
134 results on '"Peter Konrad"'

1. Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study

Author

Daniel Peterson, Mark Van Poppel, Warren Boling, Perry Santos, Jason Schwalb, Howard Eisenberg, Ashesh Mehta, Heather Spader, James Botros, Frank D. Vrionis, Andrew Ko, P. David Adelson, Bradley Lega, Peter Konrad, Guillermo Calle, Fernando L. Vale, Richard Bucholz, and R. Mark Richardson

Subjects
Vagus nerve stimulation, Rheumatoid arthritis, Inflammatory reflex, Neuroimmune modulation, Medical technology, R855-855.5
Abstract

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. Methods The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study’s initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. Results Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. Conclusions The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. Trial registration NCT04539964; August 31, 2020.

Published
2024
Full Text
View/download PDF

2. MR-guided focused ultrasound thalamotomy for lithium-induced tremor: a case report and literature review

Author

Kate Gelman, Joseph Melott, Vishal Thakur, Abdul R. Tarabishy, Ana Brandt, Peter Konrad, Manish Ranjan, and Adeel A. Memon

Subjects
tremor, lithium, MR-guided focused ultrasound (MRgFUS), high-intensity focused ultrasound (HIFU), case report, Neurology. Diseases of the nervous system, RC346-429
Abstract

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor.

Published
2024
Full Text
View/download PDF

3. Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation

Author

Sebastian Loesaus, Peter Konrad Zahn, Matthias Bechtel, Justus Thomas Strauch, Dirk Buchwald, Andreas Baumann, and Dinah Maria Berres

Subjects
Nucleated red blood cells, ECMO, Mortality, Intensive care unit, Medicine
Abstract

Abstract Background The presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far. Methods As part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay. The aim of this study was to investigate the occurrence of NRBCs during ECMO support in terms of their predictive value for mortality. Results In total 30 patients (age at admission: 62.7 ± 14.3 year; 26 male; ECMO duration: 8.5 ± 5.1 days; ICU duration: 18.0 ± 14.5 days) were included. 16 patients (53.3%) died during their inpatient stay. There were no significant differences in demographic characteristics between VA- or VV- ECMO patients. NRBCs occurred in all patients while under ECMO support. NRBC value was significant higher in those who died (2299.6 ± 4356.6 µl) compared to the surviving patients (133.6 ± 218.8 µl, p

Published
2023
Full Text
View/download PDF

4. Best practices for collaborative conservation philanthropy

Author

John Sanderson, Richard Alper, Jordana Barrack, Caroline Byrd, Erik Glenn, Kristen Jespersen, Aaron Kimple, Heather Knight, Peter Konrad, Ted Kowalski, Dave Nezzie, Kristina Ortez, Chas Robles, Toni Ruth, David Smith, Nancy Steele, Tim Stevens, Gerald Wagner, and Jessica Archibald

Subjects
American west, capacity building, collaboration, collaborative conservation, collaborative infrastructure, conservation organizations, Ecology, QH540-549.5, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Abstract Collaborative conservation brings diverse stakeholders together to sustain healthy landscapes and strengthen communities. Organizations fostering collaborative conservation depend on philanthropy to advance collaborative conservation, while philanthropic organizations depend on these organizations to advance their missions. Both face challenges engaging with each other as they work toward shared goals, yet open dialogue about how funders and practitioners work together is rare. The authors of this paper represent equal numbers of funders and practitioners who, together, identified eight best practices that are practical, effective actions funders and practitioners can take to better achieve shared conservation goals. These eight best practices are: (1) collaborate, (2) nurture relationships, (3) invest in capacity, (4) plan well, implement well, (5) engage diversity, (6) support entrepreneurial spirit, (7) reduce burdens, and (8) tell our story. By centering around collaboration, relationships, and diversity, these best practices exemplify several growing and valuable trends in philanthropy that support collaborative conservation.

Published
2022
Full Text
View/download PDF

5. Predicting poor postoperative acute pain outcome in adults: an international, multicentre database analysis of risk factors in 50,005 patients

Author

Alexander Schnabel, Maryam Yahiaoui-Doktor, Winfried Meissner, Peter Konrad Zahn, and Esther Miriam Pogatzki-Zahn

Subjects
Anesthesiology, RD78.3-87.3
Abstract

Abstract. Background:. The aim of this study was to determine simple risk factors for severe pain intensity (≥7 points on a numeric rating scale [NRS]), to analyse their relation to other patient-reported outcome measures and to develop a simple prediction model. Methods:. We used data from 50,005 patients from the PAIN-OUT project. Within a first data set (n = 33,667), relevant risk factors were identified by logistic binary regression analysis, assessed for additional patient-reported outcome measures beyond pain intensity and summed up for developing a simple risk score. Finally, sum of factors was plotted against postoperative pain outcomes within a validation data set (n = 16,338). Results:. Odds ratios (OR) for the following risk factors were identified: younger age (90 minutes, OR: 1.308), preoperative opioid intake (OR: 1.250), feeling anxious (OR: 1.239) and feeling helpless due to pain (OR: 1.198), and the country of the recruiting centre (OR: 1.919). Patients with ≥3 risk factors had more severe pain intensity scores, spent a longer time in severe pain, and wished to have received more pain treatment (P < 0.001). A simple risk score was created with 4 risk factors showing a moderate prediction level. Conclusions:. Patients with ≥3 risk factors are at higher risk for poor postoperative acute pain outcome after surgery. Future studies using this score might show that preventive strategies might decrease pain intensity, pain-related postoperative dysfunction, and the development of chronic pain.

Published
2020
Full Text
View/download PDF

6. Implantable brain computer interface: Challenges to neurotechnology translation

Author

Peter Konrad and Todd Shanks

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.

Published
2010
Full Text
View/download PDF

7. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

Author

Sara Hägg, Mehran Salehpour, Peri Noori, Jesper Lundström, Göran Possnert, Rabbe Takolander, Peter Konrad, Stefan Rosfors, Arno Ruusalepp, Josefin Skogsberg, Jesper Tegnér, and Johan Björkegren

Subjects
Medicine, Science
Abstract

BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14)C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques. METHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14)C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p

Published
2011
Full Text
View/download PDF

8. Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.

Author

Sara Hägg, Josefin Skogsberg, Jesper Lundström, Peri Noori, Roland Nilsson, Hua Zhong, Shohreh Maleki, Ming-Mei Shang, Björn Brinne, Maria Bradshaw, Vladimir B Bajic, Ann Samnegård, Angela Silveira, Lee M Kaplan, Bruna Gigante, Karin Leander, Ulf de Faire, Stefan Rosfors, Ulf Lockowandt, Jan Liska, Peter Konrad, Rabbe Takolander, Anders Franco-Cereceda, Eric E Schadt, Torbjörn Ivert, Anders Hamsten, Jesper Tegnér, and Johan Björkegren

Subjects
Genetics, QH426-470
Abstract

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P

Published
2009
Full Text
View/download PDF

10. Totius Americae Descriptio Nova.

Author

Monath, Peter Konrad and Monath, Peter Konrad

Subjects
America Maps Early works to 1800., Amérique Cartes Ouvrages avant 1800., America.
Published
2024

14. Subcortical correlates of consciousness with human single neuron recordings

Author

Michael Pereira, Nathan Faivre, Fosco Bernasconi, Nicholas Brandmeir, Jacob Suffridge, Kaylee Tran, Shuo Wang, Victor Finomore, Peter Konrad, Ali Rezai, Olaf Blanke, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and European Project: 803122,ERC-2018-STG,MetAction(2019)

Subjects
perceptual consciousness, [SCCO]Cognitive science, detection, single neuron activity, deep brain stimulation
Abstract

SummaryHow does neuronal activity give rise to our conscious experience of the outside world? This question has fascinated philosophers for centuries and is being increasingly addressed empirically. Current methods to investigate theneural correlates of consciousnessaim at contrasting the neural activity associated with different percepts under constant sensory stimulation to identify the minimal set of neuronal events sufficient for a specific conscious percept to occur (1–3). Only very few studies have found such contrasts at the single neuron level (4–8) but did so only in cortical regions of humans capable of providing subjective reports. The role of subcortical structures for perceptual consciousness is theoretically relevant (2,9,10) with some empirical support from studies in non-human primates (11,12), as well as functional imaging or local field potentials in humans (13,14). Nonetheless, it remains unknown whether and how the firing rate of subcortical neurons changes when a stimulus is consciously perceived. Here, we recorded individual neurons from the subthalamic nucleus (STN) and thalamus of human participants during 36 deep brain stimulation surgeries. While participants detected vibrotactile stimuli provided at the perceptual threshold, we found that neurons in both subcortical structures were modulated by the onset of the task or of the stimulus. Importantly, we found that 23% of the recorded neurons changed their activity when a stimulus was consciously perceived. Our results provide direct neurophysiological evidence of the involvement of subcortical structures in perceptual consciousness, thereby calling for a less cortico-centric view of the neural correlates of consciousness.

Published
2023

17. Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial

Author

Charles Y. Liu, Jonathan Russin, David P. Adelson, Alistair Jenkins, Omar Hilmi, Benjamin Brown, Bradley Lega, Tony Whitworth, Dev Bhattacharyya, Theodore H. Schwartz, Vibhor Krishna, Ziv Williams, Christopher Uff, Jon Willie, Caitlin Hoffman, William A. Vandergrift, Achal Singh Achrol, Rushna Ali, Peter Konrad, Joseph Edmonds, Daniel Kim, Pragnesh Bhatt, Brent W. Tarver, David Pierce, Ravi Jain, Chester Burress, Reema Casavant, Cecília N. Prudente, and Navzer D. Engineer

Subjects
Epilepsy, Vagus Nerve Stimulation, Stroke Rehabilitation, Anticoagulants, Vagus Nerve, General Medicine, Stroke, Treatment Outcome, Neurology, Fibrinolytic Agents, Physiology (medical), Humans, Surgery, Neurology (clinical), Platelet Aggregation Inhibitors
Abstract

Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial.The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure.The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period.This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Published
2022

19. Species-specific cutaneous protein signatures upon incision injury and correlation with distinct pain-related phenotypes in humans

Author

Segelcke, Daniel, primary, van der Burgt, Max, additional, Kappert, Christin, additional, Schmidt-Garcia, Daniela, additional, Sondermann, Julia Regina, additional, Bigalke, Stephan, additional, Pradier, Bruno, additional, Gomez-Varela, David, additional, Zahn, Peter Konrad, additional, Schmidt, Manuela, additional, and Pogatzki-Zahn, Esther Miriam, additional

Published
2022
Full Text
View/download PDF

20. Survival of Group A Streptococcus (GAS) is Enhanced Under Desiccated Culture Conditions

Author

Leonhard Menschner, Peter Konrad, Nicole Toepfner, Reinhard Berner, and Uta Falke

Subjects
Adolescent, Genotype, Streptococcus pyogenes, Population, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, Group A, Article, 03 medical and health sciences, Tonsillar crypts, Streptococcal Infections, medicine, Humans, Desiccation, Child, education, Tonsillopharyngitis, Survival rate, 030304 developmental biology, Antigens, Bacterial, 0303 health sciences, education.field_of_study, Microbial Viability, biology, 030306 microbiology, Streptococcus, Infant, Correction, Pharyngitis, General Medicine, biology.organism_classification, medicine.anatomical_structure, Child, Preschool, Reinfection, Carrier Proteins, Bacteria, Bacterial Outer Membrane Proteins
Abstract

Streptococcus pyogenes or Group A Streptococcus (GAS) infections are the leading cause of bacterial tonsillopharyngitis. The bacterium can survive and persist within the human host for a long time as it is observed in up to 40% of the population who are considered as carriers. Recurrent tonsillopharyngitis is a particular problem in children which is caused either by relapses due to failed bacterial clearance or by reinfection. A prolonged survival in tonsillar crypts or on inanimate surfaces might be sources for reinfection. We therefore examined 64 clinical GAS isolates from children with tonsillopharyngitis for their long-term survival under either liquid or desiccated culture conditions. After 6 weeks, the overall GAS survival rate was 400-fold increased under desiccated culture conditions compared to liquid culture conditions, but varied depending on the emm-type between 20-fold (emm4) and 14000-fold (emm3). The survival rates of isolates from emm75 were significantly lower which is probably due to their production of hydrogen peroxide up to fatal doses. No hydrogen peroxide production could be detected for other emm-types. Furthermore, 11 isolates from patients with recurrent tonsillopharyngitis were compared to isolates of the same emm-type from patients with single episodes of tonsillopharyngitis. A significant elevated pH value and an increased survival rate for isolates from patients with recurrent infections were observed. In conclusion, significant differences in long-term survival of different GAS isolates as well as survival under desiccated culture conditions might contribute to both failed bacterial clearance and reinfection in patients with recurrent tonsillopharyngitis.

Published
2020

24. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine Richter, Johannes Schuster, Dierk Scheinert, Andrej Schmidt, Holger Staab, Matthias Ulrich, Martin Werner, Hermann Berger, Gábor Biró, Hans-Henning Eckstein, Michael Kallmayer, Kornelia Kreiser, Alexander Zimmermann, Bärbel Berekoven, Klaus Frerker, Vera Gordon, Giovanni Torsello, Sebastian Arnold, Cora Dienel, Martin Storck, Bernhard Biermaier, Hans Martin Gissler, Christof Klötzsch, Tomas Pfeiffer, Ralph Schneider, Leander Söhl, Michael Wennrich, Angelika Alonso, Michael Keese, Christoph Groden, Andreas Cöster, Andreas Engelhardt, Christoph-Maria Ratusinski, Bengt Berg, Martin Delle, Johan Formgren, Peter Gillgren, Lotta Jarl, Torbjörn B Kall, Peter Konrad, Niklas Nyman, Claes Skiöldebrand, Johnny Steuer, Rabbe Takolander, Jonas Malmstedt, Stefan Acosta, Katarina Björses, Kerstin Brandt, Nuno Dias, Anders Gottsäter, Jan Holst, Thorarinn Kristmundsson, Tobias Kühme, Tilo Kölbel, Bengt Lindblad, Mats Lindh, Martin Malina, Tomas Ohrlander, Tim Resch, Viola Rönnle, Björn Sonesson, Margareta Warvsten, Zbigniew Zdanowski, Erik Campbell, Per Kjellin, Hans Lindgren, Johan Nyberg, Björn Petersen, Gunnar Plate, Håkan Pärsson, Peter Qvarfordt, Pavel Ignatenko, Andrey Karpenko, Vladimir Starodubtsev, Mikhail A Chernyavsky, Maria S Golovkova, Boris B Komakha, Nikolay N Zherdev, Andrey Belyasnik, Pavel Chechulov, Dmitry Kandyba, Igor Stepanishchev, Csaba Csobay-Novák, Edit Dósa, László Entz, Balázs Nemes, Zoltán Szeberin, Pál Barzó, Mihaly Bodosi, Eniko Fákó, Béla Fülöp, Tamás Németh, Szilárd Pazdernyik, Krisztina Skoba, Erika Vörös, Eleni Chatzinikou, Athanasios Giannoukas, Christos Karathanos, Stylianos Koutsias, Georgios Kouvelos, Miltiadis Matsagkas, Styliani Ralli, Christos Rountas, Nikolaos Rousas, Konstantinos Spanos, Elias Brountzos, John D Kakisis, Andreas Lazaris, Konstantinos G Moulakakis, Leonidas Stefanis, Georgios Tsivgoulis, Spyros Vasdekis, Constantine N Antonopoulos, Ion Bellenis, Dimitrios Maras, Antonios Polydorou, Victoria Polydorou, Antonios Tavernarakis, Nikolaos Ioannou, Maria Terzoudi, Miltos Lazarides, Michalis Mantatzis, Kostas Vadikolias, Lukasz Dzieciuchowicz, Marcin Gabriel, Zbigniew Krasinski, Grzegorz Oszkinis, Fryderyk Pukacki, Maciej Slowinski, Michal-Goran Stanišic, Ryszard Staniszewski, Jolanta Tomczak, Maciej Zielinski, Piotr Myrcha, Dorota Rózanski, Stanislaw Drelichowski, Wojciech Iwanowski, Katarzyna Koncewicz, Pawel Bialek, Zbigniew Biejat, Wojciech Czepel, Anna Czlonkowska, Anatol Dowzenko, Julia Jedrzejewska, Adam Kobayashi, Jerzy Leszczynski, Andrzej Malek, Jerzy Polanski, Robert Proczka, Maciej Skorski, Mieczyslaw Szostek, Piotr Andziak, Maciej Dratwicki, Robert Gil, Miroslaw Nowicki, Jaroslaw Pniewski, Jaroslaw Rzezak, Piotr Seweryniak, Pawel Dabek, Michal Juszynski, Grzegorz Madycki, Bartosz Pacewski, Witold Raciborski, Piotr Slowinski, Walerian Staszkiewicz, Martin Bombic, Vladimír Chlouba, Jirí Fiedler, Karel Hes, Petr Koštál, Jindrich Sova, Zdenek Kríž, Mojmír Prívara, Michal Reif, Robert Staffa, Robert Vlachovský, Bohuslav Vojtíšek, Tomáš Hrbác, Martin Kuliha, Václav Procházka, Martin Roubec, David Školoudík, David Netuka, Anna Šteklácová, Vladimír Beneš III, Pavel Buchvald, Ladislav Endrych, Miroslav Šercl, Walter Campos Jr, Ivan B Casella, Nelson de Luccia, André E V Estenssoro, Calógero Presti, Pedro Puech-Leão, Celso R B Neves, Erasmo S da Silva, Cid J Sitrângulo Jr, José A T Monteiro, Gisela Tinone, Marcelo Bellini Dalio, Edwaldo E Joviliano, Octávio M Pontes Neto, Mauricio Serra Ribeiro, Patrick Cras, Jeroen M H Hendriks, Mieke Hoppenbrouwers, Patrick Lauwers, Caroline Loos, Laetitia Yperzeele, Mia Geenens, Dimitri Hemelsoet, Isabelle van Herzeele, Frank Vermassen, Parla Astarci, Frank Hammer, Valérie Lacroix, André Peeters, Robert Verhelst, Silvana Cirelli, Pol Dormal, Annelies Grimonprez, Bart Lambrecht, Philipe Lerut, Eddy Thues, Guy De Koster, Quentin Desiron, Alain Maertens de Noordhout, Danielle Malmendier, Mireille Massoz, Georges Saad, Marc Bosiers, Joren Callaert, Koen Deloose, Estrella Blanco Cañibano, Beatriz García Fresnillo, Mercedes Guerra Requena, Pilar C Morata Barrado, Miguel Muela Méndez, Antonio Yusta Izquierdo, Fernando Aparici Robles, Paula Blanes Orti, Luis García Dominguez, Rafael Martínez López, Manuel Miralles Hernández, José I Tembl Ferrairo, Ángel Chamorro, Juan Macho, Víctor Obach, Vincent Riambau, Luis San Román, Frank J Ahlhelm, Kristine Blackham, Stefan Engelter, Thomas Eugster, Henrik Gensicke, Lorenz Gürke, Philippe Lyrer, Luigi Mariani, Marina Maurer, Edin Mujagic, Mandy Müller, Marios Psychogios, Peter Stierli, Christoph Stippich, Christopher Traenka, Thomas Wolff, Benjamin Wagner, Martina M Wiegert, Sandra Clarke, Michael Diepers, Ernst Gröchenig, Philipp Gruber, Andrej Isaak, Timo Kahles, Regula Marti, Krassen Nedeltchev, Luca Remonda, Nadir Tissira, Martina Valença Falcão, Gert J de Borst, Rob H Lo, Frans L Moll, Raechel Toorop, Bart H van der Worp, Evert J Vonken, Jaap L Kappelle, Ommid Jahrome, Floris Vos, Wouter Schuiling, Hendrik van Overhagen, Rudolf W M Keunen, Bob Knippenberg, Jan J Wever, Jan W Lardenoije, Michel Reijnen, Luuk Smeets, Steven van Sterkenburg, Gustav Fraedrich, Elke Gizewski, Ingrid Gruber, Michael Knoflach, Stefan Kiechl, Barbara Rantner, Timur Abdulamit, Patrice Bergeron, Raymond Padovani, Jean-Christophe Trastour, Jean-Marie Cardon, Anne Le Gallou-Wittenberg, Eric Allaire, Jean-Pierre Becquemin, Frédéric Cochennec-Paliwoda, Pascal Desgranges, Hassan Hosseini, Hicham Kobeiter, Jean Marzelle, Mohammed A Almekhlafi, Simerpreet Bal, Phillip A Barber, Shelagh B Coutts, Andrew M Demchuk, Muneer Eesa, Michelle Gillies, Mayank Goyal, Michael D Hill, Mark E Hudon, Anitha Jambula, Carol Kenney, Gary Klein, Marie McClelland, Alim Mitha, Bijoy K Menon, William F Morrish, Steven Peters, Karla J Ryckborst, Greg Samis, Supriya Save, Eric E Smith, Peter Stys, Suresh Subramaniam, Garnette R Sutherland, Tim Watson, John H Wong, L Zimmel, Vojko Flis, Jože Matela, Kazimir Miksic, Franko Milotic, Božidar Mrdja, Barbara Stirn, Erih Tetickovic, Mladen Gasparini, Anton Grad, Ingrid Kompara, Zoren Miloševic, Veronika Palmiste, Toomas Toomsoo, Balzhan Aidashova, Nursultan Kospanov, Roman Lyssenko, Daulet Mussagaliev, Rafi Beyar, Aaron Hoffman, Tony Karram, Arthur Kerner, Eugenia Nikolsky, Samy Nitecki, Silva Andonova, Chavdar Bachvarov, Vesko Petrov, Ivan Cvjetko, Vinko Vidjak, Damir Halužan, Mladen Petrunic, Bao Liu, Chang-Wei Liu, Daniel Bartko, Peter Beno, František Rusnák, Kamil Zelenák, Masayuki Ezura, Takashi Inoue, Naoto Kimura, Ryushi Kondo, Yasushi Matsumoto, Hiroaki Shimizu, Hidenori Endo, Eisuke Furui, Søren Bakke, Kristen Krohg-Sørensen, Terje Nome, Mona Skjelland, Bjørn Tennøe, João Albuquerque e Castro, Gonçalo Alves, Frederico Bastos Gonçalves, José de Aragão Morais, Ana C Garcia, Hugo Valentim, Leonor Vasconcelos, Fernando Belcastro, Fernando Cura, Patricio Zaefferer, Foad Abd-Allah, Mohamed H Eldessoki, Hussein Heshmat Kassem, Haytham Soliman Gharieb, Mary P Colgan, Syed N Haider, Joe Harbison, Prakash Madhavan, Dermot Moore, Gregor Shanik, Viviane Kazan, Munier Nazzal, Vicki Ramsey-Williams, ACST-2 Collaborative Group, Group, ACST-2 Collaborative, Halliday A., Bulbulia R., Bonati L.H., Chester J., Cradduck-Bamford A., Peto R., Pan H., Potter J., Henning Eckstein H., Farrell B., Flather M., Mansfield A., Mihaylova B., Rahimi K., Simpson D., Thomas D., Sandercock P., Gray R., Molyneux A., Shearman C.P., Rothwell P., Belli A., Herrington W., Judge P., Leopold P., Mafham M., Gough M., Cao P., MacDonald S., Bari V., Berry C., Bradshaw S., Brudlo W., Clarke A., Cox R., Fathers S., Gaba K., Gray M., Hayter E., Holliday C., Kurien R., Lay M., le Conte S., McManus J., Madgwick Z., Morris D., Munday A., Pickworth S., Ostasz W., Poorthuis M., Richards S., Teixeira L., Tochlin S., Tully L., Wallis C., Willet M., Young A., Casana R., Malloggi C., Odero A., Silani V., Parati G., Malchiodi G., Malferrari G., Strozzi F., Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca T., Tsolaki E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath S., Lambert D., Lees T., Louw S., McCaslin J., Parr N., Robson R., Stansby G., Wales L., Wealleans V., Wilson L., Wyatt M., Baht H., Balogun I., Burger I., Cosier T., Cowie L., Gunathilagan G., Hargroves D., Insall R., Jones S., Rudenko H., Schumacher N., Senaratne J., Thomas G., Thomson A., Webb T., Brown E., Esisi B., Mehrzad A., MacSweeney S., McConachie N., Southam A., Sunman W., Abdul-Hamiq A., Bryce J., Chetter I., Ettles D., Lakshminarayan R., Mitchelson K., Rhymes C., Robinson G., Scott P., Vickers A., Ashleigh R., Butterfield S., Gamble E., Ghosh J., McCollum C.N., Welch M., Welsh S., Wolowczyk L., Donnelly M., D'Souza S., Egun A.A., Gregary B., Joseph T., Kelly C., Punekar S., Rahi M.A., Raj S., Seriki D., Thomson G., Brown J., Durairajan R., Grunwald I., Guyler P., Harman P., Jakeways M., Khuoge C., Kundu A., Loganathan T., Menon N., Prabakaran R.O., Sinha D., Thompson V., Tysoe S., Briley D., Darby C., Hands L., Howard D., Kuker W., Schulz U., Teal R., Barer D., Brown A., Crawford S., Dunlop P., Krishnamurthy R., Majmudar N., Mitchell D., Myint M.P., O'Brien R., O'Connell J., Sattar N., Vetrivel S., Beard J., Cleveland T., Gaines P., Humphreys J., Jenkins A., King C., Kusuma D., Lindert R., Lonsdale R., Nair R., Nawaz S., Okhuoya F., Turner D., Venables G., Dorman P., Hughes A., Jones D., Mendelow D., Rodgers H., Raudoniitis A., Enevoldson P., Nahser H., O'Brien I., Torella F., Watling D., White R., Brown P., Dutta D., Emerson L., Hilltout P., Kulkarni S., Morrison J., Poskitt K., Slim F., Smith S., Tyler A., Waldron J., Whyman M., Bajoriene M., Baker L., Colston A., Eliot-Jones B., Gramizadeh G., Lewis-Clarke C., McCafferty L., Oliver D., Palmer D., Patil A., Pegler S., Ramadurai G., Roberts A., Sargent T., Siddegowda S., Singh-Ranger R., Williams A., Williams L., Windebank S., Zuromskis T., Alwis L., Angus J., Asokanathan A., Fornolles C., Hardy D., Hunte S., Justin F., Phiri D., Mitabouana-Kibou M., Sekaran L., Sethuraman S., Tate M.L., Akyea-Mensah J., Ball S., Chrisopoulou A., Keene E., Phair A., Rogers S., Smyth J.V., Bicknell C., Chataway J., Cheshire N., Clifton A., Eley C., Gibbs R., Hamady M., Hazel B., James A., Jenkins M., Khanom N., Lacey A., Mireskandari M., O'Reilly J., Pereira A., Sachs T., Wolfe J., Davey P., Rogers G., Smith G., Tervit G., Nichol I., Parry A., Young G., Ashley S., Barwell J., Dix F., Nor A.M., Parry C., Birt A., Davies P., George J., Graham A., Jonker L., Kelsall N., Potts C., Wilson T., Crinnion J., Cuenoud L., Aleksic N., Babic S., Ilijevski N., Radak, Sagic D., Tanaskovic S., Colic M., Cvetic V., Davidovic L., Jovanovic D.R., Koncar I., Mutavdzic P., Sladojevic M., Tomic I., Debus E.S., Grzyska U., Otto D., Thomalla G., Barlinn J., Gerber J., Haase K., Hartmann C., Ludwig S., Putz V., Reeps C., Schmidt C., Weiss N., Werth S., Winzer S., Gemper J., Gunther A., Heiling B., Jochmann E., Karvouniari P., Klingner C., Mayer T., Schubert J., Schulze-Hartung F., Zanow J., Bausback Y., Borger F., Botsios S., Branzan D., Braunlich S., Holzer H., Lenzer J., Piorkowski C., Richter N., Schuster J., Scheinert D., Schmidt A., Staab H., Ulrich M., Werner M., Berger H., Biro G., Eckstein H.-H., Kallmayer M., Kreiser K., Zimmermann A., Berekoven B., Frerker K., Gordon V., Torsello G., Arnold S., Dienel C., Storck M., Biermaier B., Gissler H.M., Klotzsch C., Pfeiffer T., Schneider R., Sohl L., Wennrich M., Alonso A., Keese M., Groden C., Coster A., Engelhardt A., Ratusinski C.-M., Berg B., Delle M., Formgren J., Gillgren P., Jarl L., Kall T.B., Konrad P., Nyman N., Skioldebrand C., Steuer J., Takolander R., Malmstedt J., Acosta S., Bjorses K., Brandt K., Dias N., Gottsater A., Holst J., Kristmundsson T., Kuhme T., Kolbel T., Lindblad B., Lindh M., Malina M., Ohrlander T., Resch T., Ronnle V., Sonesson B., Warvsten M., Zdanowski Z., Campbell E., Kjellin P., Lindgren H., Nyberg J., Petersen B., Plate G., Parsson H., Qvarfordt P., Ignatenko P., Karpenko A., Starodubtsev V., Chernyavsky M.A., Golovkova M.S., Komakha B.B., Zherdev N.N., Belyasnik A., Chechulov P., Kandyba D., Stepanishchev I., Csobay-Novak C., Dosa E., Entz L., Nemes B., Szeberin Z., Barzo P., Bodosi M., Fako E., Fulop B., Nemeth T., Pazdernyik S., Skoba K., Voros E., Chatzinikou E., Giannoukas A., Karathanos C., Koutsias S., Kouvelos G., Matsagkas M., Ralli S., Rountas C., Rousas N., Spanos K., Brountzos E., Kakisis J.D., Lazaris A., Moulakakis K.G., Stefanis L., Tsivgoulis G., Vasdekis S., Antonopoulos C.N., Bellenis I., Maras D., Polydorou A., Polydorou V., Tavernarakis A., Ioannou N., Terzoudi M., Lazarides M., Mantatzis M., Vadikolias K., Dzieciuchowicz L., Gabriel M., Krasinski Z., Oszkinis G., Pukacki F., Slowinski M., Stanisic M.-G., Staniszewski R., Tomczak J., Zielinski M., Myrcha P., Rozanski D., Drelichowski S., Iwanowski W., Koncewicz K., Bialek P., Biejat Z., Czepel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Leszczynski J., Malek A., Polanski J., Proczka R., Skorski M., Szostek M., Andziak P., Dratwicki M., Gil R., Nowicki M., Pniewski J., Rzezak J., Seweryniak P., Dabek P., Juszynski M., Madycki G., Pacewski B., Raciborski W., Slowinski P., Staszkiewicz W., Bombic M., Chlouba V., Fiedler J., Hes K., Kostal P., Sova J., Kriz Z., Privara M., Reif M., Staffa R., Vlachovsky R., Vojtisek B., Hrbac T., Kuliha M., Prochazka V., Roubec M., Skoloudik D., Netuka D., Steklacova A., Benes III V., Buchvald P., Endrych L., Sercl M., Campos W., Casella I.B., de Luccia N., Estenssoro A.E.V., Presti C., Puech-Leao P., Neves C.R.B., da Silva E.S., Sitrangulo C.J., Monteiro J.A.T., Tinone G., Bellini Dalio M., Joviliano E.E., Pontes Neto O.M., Serra Ribeiro M., Cras P., Hendriks J.M.H., Hoppenbrouwers M., Lauwers P., Loos C., Yperzeele L., Geenens M., Hemelsoet D., van Herzeele I., Vermassen F., Astarci P., Hammer F., Lacroix V., Peeters A., Verhelst R., Cirelli S., Dormal P., Grimonprez A., Lambrecht B., Lerut P., Thues E., De Koster G., Desiron Q., Maertens de Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M

Subjects
Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Published
2021

25. Hydrogen Peroxide Production of Group A Streptococci (GAS) is emm-Type Dependent and Increased at Low Temperatures

Author

Uta Falke, Reinhard Berner, Leonhard Menschner, Nicole Toepfner, and Peter Konrad

Subjects
Streptococcus pyogenes, Catabolite repression, Bacillus subtilis, Biology, Applied Microbiology and Biotechnology, Microbiology, Mixed Function Oxygenases, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Streptococcal Infections, Consensus sequence, Humans, Hydrogen peroxide, Incubation, Gene, 030304 developmental biology, chemistry.chemical_classification, Antigens, Bacterial, 0303 health sciences, 030306 microbiology, Temperature, Gene Expression Regulation, Bacterial, Hydrogen Peroxide, General Medicine, Oxidants, biology.organism_classification, Repressor Proteins, Enzyme, Biochemistry, chemistry, CCPA, Carrier Proteins, Energy Metabolism, Bacterial Outer Membrane Proteins
Abstract

Group A streptococcus (GAS) is an important human pathogen whose clinical isolates differ in their ability to produce hydrogen peroxide (H2O2). H2O2 is primarily produced by the enzyme lactate oxidase (LctO), an in depth in silico research revealed that all genome-sequenced GAS possess the required gene lctO. The importance of lctO for GAS is underlined by its highly conserved catabolite control element (cre box) as well as its perfect promotor sequence in comparison to the known consensus sequences of the Gram-positive model organism Bacillus subtilis. In this study, we provide further insight in the function and regulation of lactate oxidase by analyzing a large group of clinical GAS isolates. We found that H2O2 production increased over time in the late stationary phase; after 4 days of incubation, 5.4% of the isolates showed a positive result at 37 °C, while the rate increased to 16.4% at 20 °C. This correlation between H2O2 production and low temperatures suggests additional regulatory mechanisms for lctO besides catabolite control protein A (CcpA) and indicates that lctO might play a role for GAS energy metabolism at sub-body temperatures. Furthermore, we could identify that H2O2 production was different among clinical isolates; we could correlate H2O2 production to emm-types, indicating that emm-types 6 and 75 had the highest rate of H2O2 production. The emm-type- and temperature-dependent H2O2 production of clinical GAS isolates might contribute to their different survival strategies.

Published
2019

29. Correction to: Survival of Group A Streptococcus (GAS) is Enhanced Under Desiccated Culture Conditions

Author

Nicole Toepfner, Peter Konrad, Leonhard Menschner, Uta Falke, and Reinhard Berner

Subjects
Credit line, Third party, Statutory law, Law, Reproduction (economics), Internet portal, General Medicine, Creative commons, Biology, Applied Microbiology and Biotechnology, Microbiology, License
Abstract

The article “Survival of Group A Streptococcus (GAS) is Enhanced Under Desiccated Culture Conditions”, written by Leonhard Menschner, Uta Falke, Peter Konrad, Nicole Toepfner, Reinhard Berner, was originally published electronically on the publisher's internet portal on 2 April 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 4 June 2021 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0.

Published
2021

31. PyDapsys: an open-source library for accessing electrophysiology data recorded with DAPSYS

Author

Peter Konradi, Alina Troglio, Ariadna Pérez Garriga, Aarón Pérez Martín, Rainer Röhrig, Barbara Namer, and Ekaterina Kutafina

Subjects
interoperability, open data, FAIR, data management tools, reverse-engineered, microneurography, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

In the field of neuroscience, a considerable number of commercial data acquisition and processing solutions rely on proprietary formats for data storage. This often leads to data being locked up in formats that are only accessible by using the original software, which may lead to interoperability problems. In fact, even the loss of data access is possible if the software becomes unsupported, changed, or otherwise unavailable. To ensure FAIR data management, strategies should be established to enable long-term, independent, and unified access to data in proprietary formats. In this work, we demonstrate PyDapsys, a solution to gain open access to data that was acquired using the proprietary recording system DAPSYS. PyDapsys enables us to open the recorded files directly in Python and saves them as NIX files, commonly used for open research in the electrophysiology domain. Thus, PyDapsys secures efficient and open access to existing and prospective data. The manuscript demonstrates the complete process of reverse engineering a proprietary electrophysiological format on the example of microneurography data collected for studies on pain and itch signaling in peripheral neural fibers.

Published
2023
Full Text
View/download PDF

36. Outcome After Nitinol Stenting in the Superficial Femoral and Popliteal Artery in an Elderly Population

Author

David Lindström, Hans Pettersson, Martin Delle, Mårten Falkenberg, Peter Gillgren, Johan Fernström, and Peter Konrad

Subjects
Male, Time Factors, medicine.medical_treatment, Kaplan-Meier Estimate, Ischemia, Recurrence, Risk Factors, Popliteal Artery, Registries, Aged, 80 and over, Ultrasonography, Doppler, Duplex, education.field_of_study, Hazard ratio, Age Factors, General Medicine, Limb Salvage, Femoral Artery, Treatment Outcome, Female, Stents, Radiology, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Population, Arterial Occlusive Diseases, Prosthesis Design, Risk Assessment, Duplex scanning, medicine.artery, Alloys, medicine, Humans, education, Vascular Patency, Aged, Proportional Hazards Models, Retrospective Studies, Sweden, Chi-Square Distribution, business.industry, Angioplasty, Stent, Critical limb ischemia, Popliteal artery, Surgery, Amputation, Claudication, business
Abstract

Background To assess outcomes in an elderly and diseased population after stenting in the femoropopliteal segment and evaluate risk factors for poor prognosis. Methods Retrospective study of femoropopliteal stents placed between March 2006 and January 2008. Patency was verified by duplex scanning. Risk factors associated with amputation or death and patency were analyzed using Cox regression. Results A total of 117 limbs in 112 patients were observed for a median of 18 months. Median age of the patients was 79 years; 68% were treated for critical limb ischemia and 85% had occlusive lesions. Mean lesion length was 15.4 cm (SD: 9.2) and mean stented length was 19.7 cm (standard deviation: 9.8). At 1 year, primary patency was 63%, primary-assisted patency was 67%, and secondary patency was 69%. Stent diameter ≤6 versus 7 mm was a risk factor for loss of patency with a hazard ratio (HR) of 2.9 (95% CI: 1.1-7.7). Significant risk factors for death or amputation were as follows: HR for rest pain versus claudication was 5.9 (1.1-32.8), HR for tissue loss versus claudication was 5.8 (1.1-29.6), HR for stent diameter ≤6 versus 7 mm was 3.6 (1.0-12.3), and HR for 3-4 stents versus 1-2 was 2.6 (1.1-6.1). Conclusion Rutherford status is associated with death or amputation after stenting in the femoropopliteal segment. In addition, a smaller stent diameter and number of stents depict poorer prognosis independent of gender and anatomic level.

Published
2011

37. Microstructure Modification

Author

Simon Reichstein, Peter Konrad, Frank Dörnenburg, and Scott Kenningley

Subjects
Materials science, Metallurgy, chemistry.chemical_element, Combustion, Microstructure, law.invention, High stress, Diesel fuel, Piston, chemistry, Aluminium, law, Management of Technology and Innovation, Scientific method, Automotive Engineering, Homologous temperature
Abstract

Pressure and temperature in internal combustion engines have rapidly increased during the past 15 years. Operating at maximum temperatures of up to 420 °C in series production engines (which is equivalent to a homologous temperature of 0.92!), light vehicle diesel pistons for modern passenger vehicles probably represent aluminium’s most challenging hightemperature application. To meet these requirements, Federal Mogul has developed the process of local remelting for critical piston regions. The technical benefit of the remelt process has been proven by engine validation.

Published
2008

38. WIRBELSÄULE IM SPORT

Author

Peter Konrad, Jürgen Freiwald, and Birgit Schulte-Frei

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, Orthopedics and Sports Medicine, Physical Therapy, Sports Therapy and Rehabilitation, business
Abstract

Zusammenfassung Im Rahmen von Trainingskonzepten fur die Rumpfmuskulatur werden 3 bewahrte Konzepte erortert: Klassische Funktionsgymnastik , Training der segmentalen Stabilitat und apparative Ruckenstrasen . Ausgehend vom Modell der muskularen Sicherung der Wirbelsaule werden Grundlagen der segmentalen Stabilisierung der Lendenwirbelsaule erortert. Hierbei kommt der transversalen Stabilisierung der Lumbalregion mittels tiefer Bauch- und Ruckenmuskeln eine besondere Bedeutung zu. Funktionsgymnastische Konzeptionen zielen primar auf die Verbesserung muskularer (Dys-) Balanceverhaltnisse auserer, globaler Muskeln. Apparative Konzeptionen sind durch Ubungen mit muskularem Isolationscharakter und guter Dosierbarkeit gekennzeichnet, was insbesondere beim Leistungssport und in der Ruckenrehabilitation von Bedeutung ist.

Published
2004

40. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin

Author

Jesper Lundström, Stefan Rosfors, Arno Ruusalepp, Peri Noori, Josefin Skogsberg, Johan Björkegren, Mehran Salehpour, Göran Possnert, Peter Konrad, Sara Hägg, Jesper Tegnér, and Rabbe Takolander

Subjects
Carotid Artery Diseases, Male, Pathology, Anatomy and Physiology, Microarrays, medicine.medical_treatment, lcsh:Medicine, Cardiovascular, Mass Spectrometry, Blood plasma, Insulin, Carotid Stenosis, Myocardial infarction, lcsh:Science, Stroke, Multidisciplinary, Physics, Genomics, Immunohistochemistry, Plaque, Atherosclerotic, Medicine, Female, Plasma insulin, Immunohistochemical Analysis, Research Article, Nuclear Decay, medicine.medical_specialty, Histology, Immunology, Endocrine System, In Vitro Techniques, Vascular Biology, Internal medicine, medicine, Humans, Thrombus, Biology, Aged, Nuclear Physics, Endocrine Physiology, business.industry, lcsh:R, Computational Biology, medicine.disease, Atherosclerosis, Stenosis, Endocrinology, Immunologic Techniques, lcsh:Q, business, Genome Expression Analysis
Abstract

Background: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric C-14-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques. Methodology/Principal Finding: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for C-14 content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6+/-3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p=0.0014). Most plaques were echo-lucent rather than echo-rich (2.2460.97, range 1-5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8+/-12.4 vs. 50.4+/-6.2, p=0.00005; 57.6+/-26.1 vs. 39.8+/-25.7, p

Published
2011

41. Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study

Author

Ulf Lockowandt, Björn Brinne, Sara Hägg, Anders Hamsten, Jesper Lundström, Johan Björkegren, Lee M. Kaplan, Eric E. Schadt, Jesper Tegnér, Ulf de Faire, Maria Bradshaw, Bruna Gigante, Ming-Mei Shang, Peter Konrad, Karin Leander, Vladimir B. Bajic, Angela Silveira, Roland Nilsson, Ann Samnegård, Rabbe Takolander, Peri Noori, Jan Liska, Shohreh Maleki, Anders Franco-Cereceda, Torbjörn Ivert, Stefan Rosfors, Josefin Skogsberg, and Hua Zhong

Subjects
Male, Cancer Research, Pathology, Cardiovascular Disorders/Coronary Artery Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, Cohort Studies, Coronary artery bypass surgery, Mice, 0302 clinical medicine, Cell Movement, Gene cluster, Gene expression, Leukocytes, Cluster Analysis, Gene Regulatory Networks, Genetics (clinical), Regulation of gene expression, 0303 health sciences, Genetics and Genomics/Gene Expression, Anatomy, LIM Domain Proteins, 3. Good health, Carotid Arteries, Organ Specificity, Female, medicine.symptom, Research Article, medicine.medical_specialty, lcsh:QH426-470, Inflammation, Biology, Computational Biology/Molecular Genetics, 03 medical and health sciences, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Coronary atherosclerosis, 030304 developmental biology, Aged, Sweden, Gene Expression Profiling, Computational Biology, Endothelial Cells, Reproducibility of Results, medicine.disease, Atherosclerosis, Gene expression profiling, lcsh:Genetics, Gene Expression Regulation, Transcription Factors
Abstract

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P, Author Summary The WHO predicts that coronary artery disease (CAD) will become the leading cause of death worldwide in 2010. Currently, major research efforts are focused on understanding the genetics of CAD through multi-center, genome-wide association studies of tens of thousands of patients and controls. Such studies can identify common variants of general importance throughout the entire population, which are likely relatively few. The number of rare genetic variants and variants that act in the context of environmental risk factors for CAD is probably much higher. We performed whole-genome expression analyses in several organs to identify functionally associated genes important for CAD development. We found an atherosclerosis module (A-module) consisting of 128 genes, enriched with genetic risk for CAD, involving transendothelial migration of leukocytes (TEML) and LIM domain binding 2 (LDB2) as its high-hierarchy regulator. Our study design represents a novel way of understanding the molecular underpinnings of CAD, focusing on genome-wide expression sensing both environmental and genetic influences. Investigating the relative enrichment of genetic CAD risk in functional groups (modules and networks) is an alternative approach to extract additional relevant information from genome-wide association studies. The A-module and LDB2 are attractive targets for treatments to modulate TEML and atherosclerosis development.

Published
2009

42. Combined optical and electrical stimulation of neural tissue in vivo

Author

Peter Konrad, Jonathan M. Cayce, E. Duco Jansen, Austin R. Duke, Anita Mahadevan-Jansen, and Jonathan D. Malphrus

Subjects
Male, Materials science, genetic structures, Infrared Rays, Models, Neurological, Biomedical Engineering, Stimulation, Stimulus (physiology), law.invention, Biomaterials, Rats, Sprague-Dawley, Optics, law, Animals, Nerve Tissue, Subthreshold conduction, business.industry, Depolarization, Neural engineering, Neurophysiology, JBO Letters, Laser, Sciatic Nerve, Atomic and Molecular Physics, and Optics, Electric Stimulation, Electronic, Optical and Magnetic Materials, Rats, Sensory Thresholds, Electrode, business, Photic Stimulation, Biomedical engineering
Abstract

Low-intensity, pulsed infrared light provides a novel nerve stimulation modality that avoids the limitations of traditional electrical methods such as necessity of contact, presence of a stimulation artifact, and relatively poor spatial precision. Infrared neural stimulation (INS) is, however, limited by a 2:1 ratio of threshold radiant exposures for damage to that for stimulation. We have shown that this ratio is increased to nearly 6:1 by combining the infrared pulse with a subthreshold electrical stimulus. Our results indicate a nonlinear relationship between the subthreshold depolarizing electrical stimulus and additional optical energy required to reach stimulation threshold. The change in optical threshold decreases linearly as the delay between the electrical and optical pulses is increased. We have shown that the high spatial precision of INS is maintained for this combined stimulation modality. Results of this study will facilitate the development of applications for infrared neural stimulation, as well as target the efforts to uncover the mechanism by which infrared light activates neural tissue.

Published
2009

43. A new method for creating electrophysiological maps for DBS surgery and their application to surgical guidance

Author

Srivatsan, Pallavaram, Pierre-Francois, D'Haese, Chris, Kao, Hong, Yu, Michael, Remple, Joseph, Neimat, Peter, Konrad, and Benoit, Dawant

Subjects
Prosthesis Implantation, Brain Mapping, Models, Statistical, Surgery, Computer-Assisted, Deep Brain Stimulation, Models, Neurological, Brain, Humans, Computer Simulation, Electrodes, Implanted
Abstract

Electrophysiological maps based on a Gaussian kernel have been proposed as a means to visualize response to stimulation in deep brain stimulation (DBS) surgeries. However, the Gaussian model does not represent the underlying physiological phenomenon produced by stimulation. We propose a new method to create physiological maps, which relies on spherical shell kernels. We compare our new maps to those created with Gaussian kernels and show that, on simulated data, this new approach produces more realistic maps. Experiments we have performed with real patient data show that our new maps correlate well with the underlying anatomy. Finally, we present preliminary results on an ongoing study assessing the value of these maps as pre-operative planning and intra-operative guidance tools.

Published
2008

47. Biophysical mechanisms responsible for pulsed low-level laser excitation of neural tissue

Author

E. Duco Jansen, Chris Kao, Jonathon D. Wells, Anita Mahadevan-Jansen, and Peter Konrad

Subjects
Materials science, business.industry, Free-electron laser, Depolarization, Laser, Temperature measurement, law.invention, Thermoelastic damping, law, Electric field, Optoelectronics, Irradiation, business, Excitation
Abstract

Background/Objective: The traditional method of stimulating neural activity has been based on electrical methods and remains the gold standard to date despite inherent limitations. We have previously shown a new paradigm to in vivo neural activation based on pulsed infrared light, which provides a contact-free, spatially selective, artifact-free method without incurring tissue damage that may have significant advantages over electrical stimulation in a variety of diagnostic and therapeutic applications. The goal of this study was to investigate the physical mechanism of this phenomenon, which we propose is a photo-thermal effect from transient tissue temperature changes resulting in direct or indirect activation of transmembrane ion channels causing propagation of the action potential. Methods: Rat sciatic nerve preparation was stimulated in vivo with the Holmium:YAG laser (2.12μm), Free Electron Laser (2.1μm), Alexandrite laser (690nm), and the prototype for a solid state commercial laser nerve stimulator built by Aculight (1.87μm) to determine contributions of photobiological responses from laser tissue interactions, including temperature, pressure, electric field, and photochemistry, underlying the biophysical mechanism of stimulation. Single point temperature measurements were made with a microthermocouple adjacent to the excitation site, while an infrared camera was used for 2-D radiometry of the irradiated surface. Displacement from laser-induced pressure waves or thermoelastic expansion was measured using a PS-OCT system. Results: Results exclude a direct photochemical, electric field, or pressure wave effect as the mechanism of optical stimulation. Measurements show relative small contributions from thermoelastic expansion (300 nm) with the laser parameters used for nerve stimulation. The maximum change in tissue temperature is about 9°C (average increase of 3.66 °C) at stimulation threshold radiant exposures. Conclusion: Neural activation with pulsed laser-light occurs by a transient thermally induced mechanism. Future experiments will reveal if this effect is through direct membrane interaction or facilitated through an indirect effect leading to membrane depolarization.

Published
2006

48. Juvenile Diabetes Mellitus-a Risk Factor for Postoperative Venous Thromboembolism?

Author

Siv Bornmyr, David Bergqvist, Peter Konrad, Tore Lindholm, B. Husberg, Margaret Arnadottir, and Sven-Erik Bergentz

Subjects
Adult, Male, Risk, medicine.medical_specialty, Postoperative Complications, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Prospective Studies, Risk factor, Kidney transplantation, Retrospective Studies, business.industry, Thrombophlebitis, medicine.disease, Kidney Transplantation, Thrombosis, humanities, Uremia, Surgery, Young age, Diabetes Mellitus, Type 1, Juvenile diabetes mellitus, Female, business, Venous thromboembolism
Abstract

In a retrospective analysis of 125 patients and a prospective evaluation of 83 patients with terminal uremia undergoing kidney transplantation, juvenile diabetes mellitus was found to be a significant risk factor for the development of postoperative thromboembolism. We found a high frequency of objectively verified thromboembolism despite the relatively young age of the patients. Besides diabetes, no other clinical risk factor differed between patients with and without thrombosis.

Published
2009

49. T

Author

Ludwig Nastansky, Oliver Kundt, Karin Anstötz, Peter Konrad, Olaf S. Geiss, Indra Harijono, Christian Weiser, Andrea Back, Bernd Scholz-Reiter, Hans Czap, Werner Mellis, Hartmut Wedekind, Rainer Unland, Wolfgang Hoffmann, Matthias Schumann, Erich Bahke, and Stephan Meyer

Published
1997

50. Das Projekt BTÖV: Bedarf für Telekooperation in öffentlichen Verwaltungen

Author

Dietrich Seibt, Joachim Niemeier, Dirk Hoyer, Helmut Krcmar, Karin Gräslund, Peter Konrad, Gerhard Schwabe, Brigitte Baldi, and Werner Brettreich-Teichmann

Abstract

Die neuen Technologien fur die Telekooperation — speziell multimediale Teledienste — eroffnen Chancen fur eine bessere Organisation der Arbeit. Zukunftig wird es moglich sein, schneller, flexibler, effizienter und effektiver uber grosere Entfernungen zu kommunizieren und zusammenzuarbeiten. Deshalb werden seit dem Bundestagsbeschlus uber die Aufteilung der Hauptstadtfunktionen zwischen Bonn und Berlin die Moglichkeiten der Technikunterstutzung des “Informationsverbundes Bonn - Berlin (IVBB)” und daruber hinaus der Telekooperation zwischen geographisch verteilten Verwaltungen, Amtern, Ministerien etc. nicht nur intensiv diskutiert, sondern in konkreten Pilotprojekten vorangetrieben.

Published
1995

Catalog

Books, media, physical & digital resources
See catalog results