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1. Global Regulatory and Public Health Initiatives to Advance Pediatric Drug Development for Rare Diseases

Author: Carla, Epps, Ralph, Bax, Alysha, Croker, Dionna, Green, Andrea, Gropman, Agnes V, Klein, Hannah, Landry, Anne, Pariser, Marc, Rosenman, Michiyo, Sakiyama, Junko, Sato, Kuntal, Sen, Monique, Stone, Fumi, Takeuchi, and Jonathan M, Davis
Subjects: Biological Products, Rare Diseases, Drug Development, Public Health, Environmental and Occupational Health, Humans, Pharmacology (medical), Public Health, Child, Pandemics, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Ecosystem, COVID-19 Drug Treatment
Abstract: The literature thoroughly describes the challenges of pediatric drug development for rare diseases. This includes (1) generating interest from sponsors, (2) small numbers of children affected by a particular disease, (3) difficulties with study design, (4) lack of definitive outcome measures and assessment tools, (5) the need for additional safeguards for children as a vulnerable population, and (6) logistical hurdles to completing trials, especially with the need for longer term follow-up to establish safety and efficacy. There has also been an increasing awareness of the need to engage patients and their families in drug development processes and to address inequities in access to pediatric clinical trials. The year 2020 ushered in yet another challenge-the COVID-19 pandemic. The pediatric drug development ecosystem continues to evolve to meet these challenges. This article will focus on several key factors including recent regulatory approaches and public health policies to facilitate pediatric rare disease drug development, emerging trends in product development (biologics, molecularly targeted therapies), innovations in trial design/endpoints and data collection, and current efforts to increase patient engagement and promote equity. Finally, lessons learned from COVID-19 about building adaptable pediatric rare disease drug development processes will be discussed.
Published: 2022
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2. Hygienic analysis of violations of sanitary and epidemiological requirements for working conditions in the field of 'Mining' before and after the introduction of a risk-oriented model of control and supervisory activities (on the example of the Perm Region)

Author: Nina V. Zaitseva, Svetlana V. Klein, Ella V. Sedusova, Vitalii G. Kostarev, Vladimir M. Chigvintsev, and Ekaterina V. Maksimova
Subjects: General Medicine
Abstract: In the Russian Federation, "Mining" is a priority activity in the group "Activities in the field of industry and agriculture" for the potential risk of harm to health. The study aims to perform a hygienic analysis of violations of sanitary and epidemiological requirements for working conditions in the field of "Mining" (on the example of the Perm Region) before and after the introduction of a risk-oriented model of control and supervisory activities to manage risks to the health of the working population. Scientists performed a study according to the data of 49 inspection acts by the Rospotrebnadzor Department in the Perm Region to facilities operating in the field of "Mining," before and after the introduction of a risk-based approach (for the periods 2013-2016 and 2017-2019), using standard analysis methods. Implemented in practice in 2016, the risk-oriented approach to the control and supervision of working conditions provides for the attribution of the activities of a legal entity, an individual entrepreneur, and (or) production facilities used by them in the implementation of this activity to a particular risk category under MP 5.1.0116-17. The study used data from the Federal Register of economic entities (legal entities/sole proprietors) subject to sanitary and epidemiological supervision as of 2020; data from Rosstat and Permstat on the number of employees engaged in work with harmful and(or) dangerous working conditions, data from Rospotrebnadzor and the Department of Rospotrebnadzor in the Perm Region on occupational morbidity for 2019. The average number of violations of sanitary and epidemiological requirements to working conditions per year per economic entity in the field of Mining in the Perm Region since 2017 (since the introduction of the risk-based model of sanitary and epidemiological surveillance) has significantly decreased (p
Published: 2021
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3. Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Author: Nicole S. Bryce, Anthony T. S. Lo, Alice V. Klein, Trevor W. Hambley, and Mathew H. Todd
Subjects: Nitrile, 010405 organic chemistry, Lexitropsin, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, Anthraquinone, 0104 chemical sciences, Inorganic Chemistry, Amidine, chemistry.chemical_compound, chemistry, Anthraquinones, Cytotoxicity, Platinum, Pyrrole
Abstract: 1- and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile 'Click' reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients.
Published: 2021
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4. Efficacy and safety of panitumumab in a cohort of patients with metastatic colorectal cancer in France: PANI OUEST, a post–EMA-approval descriptive study with a geriatric oncology focus

Author: Zarrin Alavi, Véronique Guérin Meyer, Olivier Dupuis, Jean-François Ramée, Oana Cojocarasu, Fanny Marhuenda, A. Gourlaouen, Philippe Deguiral, Jean-Philippe Metges, Loïc Campion, Herve Desclos, Isabelle Cumin, Delphine Deniel Lagadec, F. Grude, Remy Barraya, V. Klein, Yann Touchefeu, Julien Edeline, Aurelie Fichet, Jean-Yves Douillard, Hélène Senellart, Xavier Artignan, Karine Bideau, Roger Faroux, Nach Eddine Achour, Marc Porneuf, Claire Stampfli, and Dominique Besson
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Colorectal cancer, Medical Oncology, Proto-Oncogene Proteins p21(ras), Antineoplastic Agents, Immunological, Internal medicine, Pharmacovigilance, Product Surveillance, Postmarketing, medicine, Humans, Panitumumab, Progression-free survival, Aged, Aged, 80 and over, business.industry, Gastroenterology, Cancer, Middle Aged, medicine.disease, Progression-Free Survival, Irinotecan, Treatment Outcome, Geriatric oncology, Geriatrics, Cohort, Female, Original Article, France, Colorectal Neoplasms, business, medicine.drug
Abstract: Background/aims The Bretagne-Pays de la Loire cancer observatory, an oncology network created by the French Ministry of Health, is specifically dedicated to assess the use of new targeted anticancer therapies in routine practice. In line with the French National Cancer III program, our cancer network set up a real-life cohort, which is independent of the pharmaceutical industry, for patients with colorectal cancer to monitor patient safety and quality of care and promote pharmacovigilance. Materials and methods Panitumumab monotherapy was assessed in 243 patients with wild-type Kirsten rat sarcoma who were treated for metastatic colorectal cancer (mCRC) between July 2008 and December 2010 after prior chemotherapy using oxaliplatine and irinotecan. This was a post-European medicine agency marketing (EMA-M) study Results: This study shed light on the best practices, strategic adaptations, clinical results (treatment objective responses, 13%; progression free survival, 2.99 months [2.73-3.15]; and overall survival, 6.8 months [5.49-8.38]) as well as expected or unexpected (grade 3 or 4: 11.5%) secondary effects in the phase IV panitumumab treatment of mCRC. Conclusion Our results are similar to those by Amado whose phase III study led to obtaining EMA-M for panitumumab and tend to confirm the antitumor activity of this antiepidermal growth factor receptor antibody in the treatment of mCRC. In addition, our results opened avenues to further assessment of panitumumab use as monotherapy as well as its benefit-risk ratio while taking into account the patients' general and clinical characteristics. In 2012, the French National Authority for Health appended these data to the panitumumab transparency committee report.
Published: 2020
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5. 'Training of special education teachers in Slovakia and Ukraine: comparative analysis'

Author: V. Šilonová, V Hladush, and V. Klein
Subjects: Medical education, Political science, Automotive Engineering, Special education, Training (civil)
Published: 2020
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6. Regulatory Verification by Health Canada of Content in Recombinant Human Insulin, Human Insulin Analog, and Porcine Insulin Drug Products in the Canadian Market Using Validated Pharmacopoeial Methods Over Nonvalidated Approaches

Author: Barry Lorbetskie, Stewart Bigelow, Lisa Walrond, Agnes V. Klein, Shih-Miin Loo, Nancy Green, Michael Rosu-Myles, Xu Zhang, Huixin Lu, Michel Girard, and Simon Sauvé
Subjects: Endocrinology, Diabetes and Metabolism, Biomedical Engineering, Internal Medicine, Bioengineering
Abstract: Background: For diabetes mellitus treatment plans, the consistency and quality of insulin drug products are crucial for patient well-being. Because biologic drugs, such as insulin, are complex heterogeneous products, the methods for drug product evaluation should be carefully validated for use. As such, these criteria are rigorously evaluated and monitored by national authorities. Consequently, reports that describe significantly lower insulin content than their label claims are a concern. This issue was raised by a past publication analyzing insulin drug products available in Canada, and, as a result, consumers and major patient organizations have requested clarification. Methods: To address these concerns, this study independently analyzed insulin drug products purchased from local Canadian pharmacies—including human insulin, insulin analogs, and porcine insulin—by compendial and noncompendial reversed-phase high-performance liquid chromatography (RP-HPLC) methods. Results: We demonstrated the importance of using methods fit for purpose when assessing insulin quality. In a preliminary screen, the expected insulin peak was seen in all products except two insulin analogs—insulin detemir and insulin degludec. Further investigation showed that this was not caused by low insulin content but insufficient solvent conditions, which demonstrated the necessity for methods to be adequately validated for product-specific use. When drug products were appropriately assessed for content using the validated type-specific compendial RP-HPLC methods for insulin quantitation, values agreed with the label claim content. Conclusions: Because insulin drug products are used daily by over a million Canadians, it is important that researchers and journals present data using methods fit for purpose and that readers evaluate such reports critically.
Published: 2023
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7. Priority risk factors of drinking water and the related with it economical loss

Author: S.A. Vekovshinina, A. S. Sboev, and Svetlana V. Klein
Subjects: 03 medical and health sciences, 0302 clinical medicine, Geography, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, 030211 gastroenterology & hepatology, General Medicine, 030204 cardiovascular system & hematology, Pollution
Abstract: The inadequate water quality of utility and drinking water supply system has been shown to be able to contribute to the additional cases of mortality (approx. 11,0 thousand cases) and morbidity (over 2900 thousand cases) and be the second most important environmental factor. Elevated levels of arsenic, copper, cadmium, organochlorine compounds, nitrates, nitrites and other detrimental impurities can give rise the development of adverse effects on skin and subcutaneous tissue; musculoskeletal system and connective tissue; blood, hematopoietic organs and separate disorders involving the immunity mechanism; urogenital, nervous, endocrine systems, blood circulatory system, digestive organs, both in the population of adults and children. The list of priority risk factors incoming with drinking water and forming negative tendencies of the health state of the population of the Russian Federation changes insignificantly over time. The economic loss due to the negative influence of the priority factors of drinking water pollution on the population’s health accounted for over 50 billion rubles in 2014.
Published: 2019
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8. SCIENTIFIC AND METHODOLOGICAL ASPECTS AND PRACTICAL EXPERIENCE FOR THE FORMATION OF THE EVIDENTIAL BASE OF HAZARD TO HEALTH IN THE POPULATION IN THE ZONE OF INFLUENCE OF WASTE FROM THE PAST ECONOMIC ACTIVITY

Author: S. V. Klein, N. V. Zaitseva, S. S. Khankharev, A. A. Boloshinova, and Irina V. May
Subjects: education.field_of_study, Health, Toxicology and Mutagenesis, Population, Public Health, Environmental and Occupational Health, General Medicine, 010501 environmental sciences, Base (topology), 01 natural sciences, Pollution, Hazard, 03 medical and health sciences, 0302 clinical medicine, Geography, 030212 general & internal medicine, education, Environmental planning, 0105 earth and related environmental sciences
Abstract: There are described an algorithm and methods for collecting the evidential base for causing hazard to the health of the population of Zakamensk (the Republic of Buryatia) in the zone of influence of the waste of the past activities of the Dzhidinsky tungsten-molybdenum combine. The source of danger is lying sands, containing a complex of toxic heavy metals - lead, cadmium, manganese, nickel, chromium, etc. The algorithm for the formation of the evidential base included: a general analysis of the sanitary and hygienic situation; assessment in the dynamics of the quality of atmospheric air, drinking water, soil, food; assessment of the risk to the health of the population; epidemiological studies; in-depth clinical surveys of a representative group of city residents (280 people). In the blood of the examinees, heavy metals were identified as biological markers of the exposure. There was evaluated a complex of the response (effect) adequate to effects of laboratory markers. By methods of mathematical statistics there was established the presence of reliable relationships in the system “source of hazard - the quality of the environment - exposure to risk factors - health status.” The hazard to the health of a citizen, due to the negative impact of the factor, was considered to be proven if it was possible to build a continuous step-by-step logical chain of relationships between the source of the harmful effect, the quality of the habitat and the establishment of the fact of the disease. The quality of the habitat of the population of Zakamensk was shown to give rise in unacceptable risks to the health of residents. The main influencing factor is the pollution of atmospheric air, local food products and drinking water from public and private wells. Risks are realized in terms of a level of the primary morbidity rate of the population of the respiratory diseases, endocrine system, digestive organs that is relatively high compared to the matched area. The relationship between health hazard and environmental factors has been fully proved in 14% of the surveyed persons. At the same time, the territory was shown not be characterized as a zone of “ecological disaster” or “an emergency environmental situation”.
Published: 2019
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9. Advanced results of Fortelyzin® use in the FRIDOM1 study and real clinical practice

Author: V. A. Markov, D. V. Duplyakov, S. L. Konstantinov, G. V. Klein, S. B. Aksentiev, D. Yu. Platonov, E. V. Vyshlov, Е. A. Ponomarev, R. M. Rabinovich, E. L. Makarov, E. V. Kulibaba, D. S. Yunevich, O. V. Kritskaya, E. A. Baranov, O. B. Talibov, V. A. Kutsenko, A. A. Orlovsky, N. L. Vyazova, A. G. Koledinsky, A. M. Semenov, M. P. Semenov, E. B. Yarovaya, T. M. Uskach, R. M. Shakhnovich, S. N. Tereshchenko, and S. S. Markin
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Aim. To study the effectiveness of Fortelyzin® in subgroups with different body weights in patients with ST-segment elevation acute myocardial infarction (STEMI) in the FRIDOM1 study and real clinical practice.Material and methods. Fortelyzin® was administered in a single-bolus dose of 15 mg over 10 seconds, regardless of the body weight of patients. Metalyse® was administered in a single-bolus dose of 30-50 mg over 10 seconds, depending on body weight. The one-year results of the FRIDOM1 study were evaluated by the clinical centers using telephone contact. Monitoring of Fortelyzin® use was carried out by inpatient physicians, emergency doctors and paramedics by filling out a monitoring sheet in the period from June 2013 to December 2021 in 19243 patients with STEMI.Results. In the FRIDOM1 study, the distribution of patients depending on body weight in the Fortelyzin® (n=190) and Metalyse® (n=191) drug groups was as follows: up to 60 kg — 4 people each (p=1,00); from 60 to 70 kg — 21 and 23 (p=0,87); from 70 to 80 kg — 39 and 43 (p=0,71), from 80 to 90 kg — 63 and 47 (p=0,07); from 90 to 100 kg — 30 and 41 (p=0,19); over 100 kg — 33 people (p=1,00) in each group. The effectiveness of thrombolysis according to electrocardiographic (ECG) data in the Fortelyzin® and Metalyse® groups was as follows: up to 60 kg — 75% each (p=1,00); from 60 to 70 kg — 76% vs 83% (p=0,72); from 70 to 80 kg — 82% vs 86% (p=0,76); from 80 to 90 kg — 81% vs 77% (p=0,64); from 90 to 100 kg — 80% vs 81% (p=1,00); over 100 kg — 79% vs 76% (p=1,00); in total — 80% vs 80% (p=0,87). The effectiveness of thrombolysis according to coronary angiography (CAG) (TIMI 2-3) in the Fortelyzin® and Metalyse® groups was as follows: up to 60 kg — 100% vs 50% (p=0,43); from 60 to 70 kg — 81% vs 67% (p=0,48); from 70 to 80 kg — 74% vs 84% (p=0,41); from 80 to 90 kg — 70% vs 72% (p=1,00); from 90 to 100 kg — 67% vs 66% (p=1,00); over 100 kg — 58% vs 64% (p=0,80); in total — 70% vs 71% (p=0,76). The one-year survival rate in the FRIDOM1 study in the Fortelyzin® and Metalyse® groups was 94% (p=0,91). The administration of Fortelyzin® in patients with STEMI caused blood flow restoration according to ECG data in 14624 of 19243 patients (76%), while according to CAG (TIMI 2-3) — in 3422 of 4805 patients (71%). Inhospital mortality was 5% (n=962), while intracranial hemorrhage developed in 0,5% (n=92).Conclusion. The use of Fortelyzin® in the FRIDOM1 study and in real clinical practice in a single-bolus (10 sec) dose of 15 mg in patients with STEMI with any body weight showed its high efficacy and safety, including at the prehospital stage.
Published: 2022
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10. An interreality study of race and homicide news coverage in Baton Rouge, Louisiana

Author: Tim V Klein and Quincy Hodges
Subjects: Cultural Studies, Arts and Humanities (miscellaneous), Communication, Law
Abstract: Building on ethnic blame discourse, the social threat hypothesis, and media bias theories, this article makes a quantitative interreality comparison between homicide news coverage and homicide statistics in Baton Rouge, Louisiana—a city with one of the highest homicide rates in the United States of America. Findings reveal that Whites made up 2% of homicide victims in 2018 in Baton Rouge, but represented almost 40% of homicide victims in the news. Press releases issued by local law enforcement also overrepresented White homicide victims, as did follow-up stories. Findings on homicide suspects showed that Whites and Latinos were overrepresented, and Blacks were underrepresented.
Published: 2022
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11. Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models

Author: Anthony T S, Lo, Nicole S, Bryce, Alice V, Klein, Mathew H, Todd, and Trevor W, Hambley
Subjects: Nylons, Organoplatinum Compounds, Cell Line, Tumor, Amidines, Humans, Anthraquinones, Antineoplastic Agents, Fluorescence, Cell Proliferation
Abstract: 1- and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile 'Click' reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients.
Published: 2020

12. Search for heavy neutral Higgs bosons produced in association with b -quarks and decaying into b -quarks at s=13 TeV with the ATLAS detector

Author: Michael Huebner, Felix Cormier, H. Kagan, Christian Johnson, K. K. Gan, Maria Giovanna Foti, Namig Javadov, Tamar Djobava, K. Ntekas, Domizia Orestano, Tetiana Hrynova, Christopher Anelli, Kristian Gregersen, Richard Bates, Sinan Kuday, Masahiro Morinaga, Mariyan Petrov, L. F. Oleiro Seabra, Adrian Chitan, Benjamin Wynne, Birgit Sylvia Stapf, Carsten Bittrich, Marko Mikuz, W. T. Fedorko, Hans Peter Beck, A. S. Thompson, John Kamal Rizk Meshreki, Markus Nordberg, A. De Salvo, Radek Novotny, Koji Terashi, Andrew Chisholm, Jorge Lopez, Vakhtang Tsiskaridze, J. N. Butler, Anyes Taffard, S. Tokar, Simone Amoroso, Benjamin Paul Jaeger, Bartosz Sebastian Dziedzic, Eric Edward Corrigan, Nicolas Ellis, Craig Buttar, M-S. Barisits, Michele Livan, Q. J. Li, Ulla Blumenschein, Annick Lleres, Catrin Bernius, Tigran Mkrtchyan, Kyungeon Choi, Alan James Taylor, Philip Phillips, Philipp Thomas Koenig, Gino Marceca, Laurent Vacavant, H. H. Williams, Giada Mancini, Corentin Allaire, G. Introzzi, Yee Chinn Yap, Sahal Yacoob, Josh Moss, Enrique Kajomovitz, M. V. Silva Oliveira, Evgenii Baldin, Louis Helary, Yiming Abulaiti, Anna Mastroberardino, Bruno Lenzi, David Kirchmeier, Nathan Peter Readioff, Maximilian Hils, Isabelle Wingerter-Seez, A. Bandyopadhyay, Alessandro Tricoli, Saime Gurbuz, Jyoti Prakash Biswal, Henrik Oppen, Juraj Bracinik, Clara Nellist, Thomas Malte Spieker, Jan Thomas Kuechler, D. Rousseau, K. Potamianos, J. Montejo Berlingen, Christopher Lester, Miha Zgubic, Giancarlo Spigo, Kathleen Whalen, Charles William Kalderon, Raimund Ströhmer, Audrey Ducourthial, Luca Colasurdo, Chase Owen Shimmin, Stefanie Morgenstern, David Paul Yallup, Francesco Cirotto, Ming Chung Chu, Nicola Semprini-Cesari, Andrew Ferrante, Magdalena Slawinska, V. O. Tikhomirov, Konstantin Beloborodov, Alexey Anisenkov, C. Garcia-Argos, Nikita Belyaev, Ann Miao Wang, G. Duckeck, R. Di Nardo, V. Andrei, Federica Legger, Antonia Strubig, Clara Troncon, David DeMarco, You Zhou, Aranzazu Ruiz-Martinez, R. Di Sipio, Chenzheng Zhu, David William Casper, D. Di Valentino, Yang Heng, Cherifa Sabrina Amrouche, F. Cerutti, Xuanhong Lou, Paul Miyagawa, Antonio Ereditato, Michele Pinamonti, Sabine Lammers, Volker Büscher, Kathryn Grimm, A. C. König, Luca Ambroz, Nikolai Marcel Hartmann, M. Morii, Wendy Jane Taylor, A. T. Goshaw, Hernan Wahlberg, Feng Lyu, V. Castillo Gimenez, Emily Nurse, Elizabeth Gallas, M. Kuze, Matthew John Baca, Moritz Kiehn, Forrest Hays Phillips, Shreya Saha, Tomas Komarek, Timothy Barklow, Daria Zieminska, Sebastian Liem, P. C. F. Glaysher, F. Yamane, Jonathan Shlomi, Sergey Kuleshov, Revital Kopeliansky, Harshna Jivan, Colleen Jennifer Treado, L. B. A. H. Hommels, Harinder Singh Bawa, Nathan Allen Grieser, Yang Gao, John Baines, Yanjun Tu, S. Prell, Maosen Zhou, Elliott Cheu, F. Lasagni Manghi, John Huth, Shuyang Hu, Ken-ichi Uchida, Ariella Cattai, Florian Christoph Fischer, Mariya Shiyakova, A. B. Fenyuk, Danilo Giugni, Mohammed Faraj, Robert J. Bielski, C. Adam Bourdarios, Oliver Kortner, Katharina Bierwagen, Denys Denysiuk, Wai Yuen Chan, Brigitte Vachon, Arthur Eugen Bolz, Rohin Narayan, J-P. Meyer, Konstantin Zhukov, Jie Zhang, Vic Vacek, Otmar Biebel, Andrei Snesarev, Elena Murielle Freundlich, Ahmimed Ouraou, Paul Mircea Gravila, Alessandro Ambler, Tobias Bisanz, Izaac Sanderswood, Remco Castelijn, D. P. C. Sankey, Emmanuel Sauvan, H. K. Hadavand, F. A. Jimenez Morales, Daniel Turgeman, Magnar Kopangen Bugge, Marcela Mikestikova, Sascha Caron, Vladimir Sulin, Y. Wu, J. E. Brau, D. Paredes Hernandez, Ren-You Zhang, David Richard Shope, Alan Litke, Jelena Krstic, Y. L. Yamaguchi, Natascha Savic, Sebastian Heer, Jörgen Sjölin, Andre Sopczak, Johnny Raine, Christopher Bee, Petr Vokac, Dingane Reward Hlaluku, Frank Ellinghaus, Yuji Minegishi, J. W. Smith, Nikolaos Rompotis, S. De Castro, Thomas Meideck, Joseph Haley, Thorben Swirski, F. Wang, Daniel Fournier, Uta Klein, Maria Smizanska, Stephen Gibson, Phillip Urquijo, Naoki Kimura, Marija Marjanovic, Friedrich Hoenig, J. S. Lange, Giancarlo Panizzo, Hannah Arnold, M. H. Genest, J. Hrivnac, R. F. Y. Peters, A. Roy, Attilio Picazio, Hasko Stenzel, Djamel Eddine Boumediene, Y. Amaral Coutinho, E. Valdes Santurio, D. Chakraborty, Zhongyukun Xu, Michael Schernau, Clement Camincher, Marzieh Bahmani, P. Grenier, Pavel Tsiareshka, Atanu Pathak, Feiyu Li, Madalyn Ann McKay, Vincent Garonne, Sandro Palestini, Didier Alexandre, Joel Hengwei Foo, Alexander David Sherman, C. H. Wang, Michel Raymond, Remi Lafaye, N. L. Abraham, Are Sivertsen Traeet, Adam Kaluza, Veronique Boisvert, A. Soffer, Antony Fray, Janna Katharina Behr, Zhi Zheng, Roberto Iuppa, Michel Lefebvre, Charles Delporte, Y. W. Liu, Peilong Wang, Takuya Nobe, Steffen Schaepe, R. Richter, Zhen Yan, Gunnar Jakel, S. H. Robertson, Jamal Eddine Derkaoui, Monica Trovatelli, A. A. E. Bannoura, Efstathios Karentzos, Ivan Sykora, Andrew Beddall, Florian Beisiegel, W. Buttinger, David Hohn, Leonardo Merola, A. Hasib, L. M. Mir, Rongkun Wang, Elliot Reynolds, Radim Slovak, Klaus Hamacher, Ludovico Pontecorvo, Alexander Cheplakov, Geert-Jan Besjes, J. P. Dietrich, D Dodsworth, Andrea Sansoni, L. K. Gladilin, Liang Li, Thorsten Wengler, Benedetto Gorini, G. Lehmann Miotto, C. M. Vergel Infante, Jelena Jovicevic, D. G. Charlton, Guy Rosin, Nurfikri Bin Norjoharuddeen, Filippo Ceradini, R. Bartoldus, C. J. S. Young, Masato Aoki, Boping Chen, Namgyun Jeong, Konstantin Belotskiy, Brianna Lynn Stamas, Liaoshan Shi, Steven Juhyung Lee, Robin Hayes, S. R. Hou, Francesco Crescioli, Valerio Vercesi, Wu S. L., Maximiliano Sioli, Marco Delmastro, Fridolin Dittus, Tom McCarthy, K. Nakamura, Aytul Adiguzel, Dmitri Tsybychev, Kim Katrin Heidegger, Dai Kobayashi, S. Chouridou, Tatiana Klioutchnikova, Grzegorz Gach, Noemi Calace, Marko Stamenkovic, Dean T. Yamaguchi, M. I. Gostkin, Deepa Thomas, George Redlinger, G. Rybkin, M. Stegler, Martine Bosman, Sergio Gonzalez-Sevilla, C. Dallapiccola, Johannes Erdmann, Emily McDonald, Josh Mcfayden, G. Mikenberg, Yi Yang, Serhat Oerdek, Leszek Adamczyk, Stephen Weber, X. Sun, Ellis Kay, Kazuki Todome, A. Lopez Solis, Elisabetta Vilucchi, J. Dickinson, J. M. Iturbe Ponce, A. Ramirez Morales, Sara Ghasemi, I. M. Gregor, Tetsuro Mashimo, Hassane Hamdaoui, KT Bauer, Lucrezia Stella Bruni, Stephane Jezequel, S. J. Sekula, Andrea Knue, Miao Liu, Luka Kanjir, Peter Charles Mcnamara, G. H. A. Viehhauser, Tomas Davidek, Michael Pitt, Giulia Gonella, Dalila Salamani, Thomas LeCompte, Philippe Mermod, Shuanggeng Wang, Wing Sheung Chan, Jeffrey David Shahinian, Stewart Martin-Haugh, Kerim Suruliz, Monika Wielers, C. F. Feng, Dimos Sampsonidis, Edson Carquin, W. J. Murray, Cigdem Issever, William James Fawcett, M. Scornajenghi, Muhammad Alhroob, Peter Johannes Falke, K Wakamiya, Oxana Smirnova, Johannes Elmsheuser, B. Martin dit Latour, Filipp Dubinin, Ferdinand Krieter, Mateusz Dyndal, Jovan Mitrevski, M. Barbero, A. Sanchez Pineda, G. Rahal, Christian Johann Riegel, P. Conde Muiño, Michel Vetterli, Adam Edward Barton, Myriam Mondragón, Sandrine Laplace, Lesya Anna Horyn, Amartya Rej, David Lynn, C. M. Robles Gajardo, Vincenzo Cavasinni, B. Pearson, C. Moreno Martinez, Anum Qureshi, Yasuyuki Horii, Vladimir Cindro, Aaron James Armbruster, Marisilvia Donadelli, Gabriele Chiodini, Pavel Murin, S. Willocq, Matthew Glenn Kurth, Nicolas Morange, Hongfang Liu, Sabrina Sacerdoti, Ewelina Lobodzinska, Philipp Horn, Christina Agapopoulou, Eric Drechsler, Leigh Schaefer, Sonia Carra, Eirik Gramstad, Nils Krumnack, D. Hayden, Fabrizio Scuri, Sergey Peleganchuk, Serguei Sivoklokov, Aaron Michael Soffa, Damiano Vannicola, Gaetano Barone, C. P. 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Leite, Hideyuki Oide, Evangelos Gazis, Adomas Jelinskas, Kazuki Motohashi, Karel Cerny, S. Tapia Araya, E Akilli, Alessandro Gabrielli, Claude Guyot, Yasuyuki Okumura, Sinead Farrington, Georg Zobernig, C. P. A. Roland, Mario Spina, Nihal Brahimi, Catalin Agheorghiesei, Yoji Hasegawa, Laura Fabbri, Alexander Emerman, K. Nagai, Iskander Ibragimov, Wen Guan, Declan Andrew Millar, Shayma Wahdan, C. Lampoudis, Andreas Petridis, Alexander Sydorenko, Patrick Fassnacht, M. Li, A. V. Akimov, DF Zhang, Ketevi Assamagan, P. D. Thompson, Herjuno Rah Nindhito, Jonathan Long, Efe Yigitbasi, K. J. R. Cormier, Jolanta Olszowska, S. A. Olivares Pino, Heather Russell, Andrew Pilkington, Vitaliano Chiarella, J. Hobbs, Chiara Grieco, H. A. Neal, Andrey Ryzhov, Guillaume Unal, Georges Azuelos, Philip Bechtle, A. Glazov, Barry King, S. C. Lee, Hannah Herde, A. Artamonov, Daniela Bortoletto, Nello Bruscino, Robert Adam Vallance, C. M. Hawkes, Pavol Bartos, Marina Cobal, Michael Edward Nelson, Fine Fiedler, Evgeny Starchenko, C. Padilla Aranda, Jiri Masik, P. F. Harrison, Oleg Fedin, Christos Leonidopoulos, V. M. M. Cairo, Stamatios Gkaitatzis, Isabel Marian Trigger, N. S. Dann, Mauro Villa, Mathieu Benoit, R. Les, Lewis James Armitage, Amir Farbin, Shigeki Hirose, D. Bakshi Gupta, Veronika Magerl, Liron Barak, Alexander Undrus, M. A. Nomura, L. Masetti, J. C. Hill, Julien-christopher Beyer, Jesse Alan Heilman, R. Piegaia, Verena Herget, Giuseppe Callea, Emma Tolley, Weimin Song, Calum Michael Macdonald, Simon Henry Connell, A. R. Buzykaev, Tatsuya Masubuchi, Oliver Keith Baker, Miroslav Myska, Blake Burghgrave, P. Morettini, A. Di Girolamo, Pavel Podberezko, Siegfried Bethke, Caterina Doglioni, J. Ocariz, Michael Backes, Adrian Buzatu, Jiri Kvita, Tobias Golling, Alexander Held, Michaela Mlynarikova, Lucas Macrorie Flores, Victoria Jane Martin, Cecile Deterre, John Alison, Sara Valentinetti, Tobias Flick, Gabriele D'amen, Val O'Shea, Laura Franconi, Aishik Ghosh, Luca Pizzimento, Pawel Klimek, Frank Winklmeier, L. R. Flores Castillo, Emily Charlotte Graham, A. Abed Abud, Luc Poggioli, R. R. M. Fletcher, F. Peri, R. de Asmundis, Marek Tasevsky, Matthias Danninger, Zara Jane Grout, Oleg Zenin, Miha Muskinja, J. Rothberg, Goetz Gaycken, Jean-Arcady Meyer, Vince Croft, Stavros Maltezos, Stefano Manzoni, Carsten Daniel Burgard, Bernd Stelzer, Maria Florencia Daneri, Kingman Cheung, Z. P. Zhang, Josu Cantero, Yoav Afik, N. B. Sinev, Bogdan Malaescu, Jad Zahreddine, Christine Kourkoumelis, Pedro Jorge, H. J. Cheng, Mauro Iodice, Lingxin Meng, Ruggero Turra, Maia Mosidze, Grigore Tarna, Konstantin Lehmann, and H. Zhu
Subjects: Quark, Physics, Particle physics, 010308 nuclear & particles physics, Atlas detector, High Energy Physics::Lattice, Nuclear Theory, High Energy Physics::Phenomenology, 01 natural sciences, 0103 physical sciences, Higgs boson, High Energy Physics::Experiment, Nuclear Experiment, 010306 general physics, Boson, Minimal Supersymmetric Standard Model
Abstract: A search for heavy neutral Higgs bosons produced in association with one or two b-quarks and decaying to b-quark pairs is presented using 27.8 fb(-1) of root s=13 TeV proton-proton collision data r ...
Published: 2020
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13. Prolonged Successful Cardiopulmonary Resuscitation with Thrombolysis in a Patient with Acute Coronary Syndrome

Author: M. A. Nikolaev, G. V. Klein, S. E. Chukseev, and A. A. Timofeev
Subjects: thrombolysis, Resuscitation, Acute coronary syndrome, business.industry, medicine.medical_treatment, Staphylokinase, recombinant non-immunogenic staphylokinase, RM1-950, Thrombolysis, medicine.disease, cardiopulmonary resuscitation, acute coronary syndrome, medicine.anatomical_structure, RC666-701, Anesthesia, medicine, Diseases of the circulatory (Cardiovascular) system, Pharmacology (medical), Therapeutics. Pharmacology, Cardiopulmonary resuscitation, Cardiology and Cardiovascular Medicine, business, Artery
Abstract: A case of successful cardiopulmonary resuscitation lasting 120 min with a good neurological outcome in a patient with acute coronary syndrome is presented. The protocol of resuscitation with the use of thrombolysis (recombinant non-immunogenic staphylokinase) followed by stenting of the infarct-dependent artery in a patient with acute coronary syndrome is described on the example of this case.
Published: 2019
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14. Fortelyzin® in comparison with Metalyse® for ST-elevated myocardial infarction: one-year results and clinical outcomes of a multicenter randomized study FRIDOM1

Author: V. A. Markov, D. V. Duplyakov, S. L. Konstantinov, G. V. Klein, S. B. Aksentev, D. Yu. Platonov, E. V. Vyshlov, E. A. Ponomarev, R. M. Rabinovich, E. L. Makarov, E. V. Kulibaba, D. S. Yunevich, O. V. Kritskaia, E. A. Baranov, O. B. Talibov, and E. A. Gerasimets
Subjects: medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, 030204 cardiovascular system & hematology, stelevated myocardial infarction, law.invention, metalyse®, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Diseases of the circulatory (Cardiovascular) system, Medicine, pharmacoinvasive strategy, 030212 general & internal medicine, Myocardial infarction, oneyear results, business.industry, Anticoagulant, Percutaneous coronary intervention, Thrombolysis, medicine.disease, RC666-701, Conventional PCI, Russian federation, Patient status, Cardiology and Cardiovascular Medicine, business, fortelyzin®
Abstract: Aim. Evaluate the oneyear results and clinical outcomes of a multicenter randomized clinical trial FRIDOM1.Material and methods. The study FRIDOM1 was conducted in 11 clinical centers of the Russian Federation in the period 20142016. The study included 382 patients with acute STelevated myocardial infarction (STEMI), who were randomly divided into the Fortelyzin® and Metalyse®. Thrombolysis was accompanied by anticoagulant and dual antiplatelet therapy followed by percutaneous coronary intervention (PCI). Oneyear patient status, allcause mortality, including cardiovascular diseases (CVD), hospitalization, and oneyear survival were assessed by telephone contact.Results. The oneyear patient status was determined in 186 out of 191 (97,4%) in the Fortelyzin® group and in 185 out of 191 (96,9%) patients in the Metalyse® group. Oneyear allcause mortality was 5,9% and 6,5% in the Fortelyzin® and Metalyse® groups, respectively (p=0,83; OR 0,91; 95% CI — 0,421,98). Oneyear mortality from CVD in the Fortelyzin® group is 5,4%, in the Metalyse® group — 6,5% (p=0,67; OR 0,83; 95% CI — 0,371,83). Allcause mortality between 30 days and 1 year in the Fortelyzin® group was in 2,2% of patients, CVD — in 1,6%, in the group of Metalise® mortality was in 2,7% of patients (all — CVD). Oneyear survival was 94,1% and 93,5% in the Fortelyzin® and Metalyse® groups, respectively.Conclusion. The oneyear results of the FRIDOM1 study showed the efficacy and safety of a single bolus administration of Fortelyzin® as part of a pharmacoinvasive strategy for treating patients with STEMI, as well as clinical outcomes that are comparable with Metalyse®, including high survival rates and low CVD mortality.
Published: 2018
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15. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author: Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. 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M., Martini, G., Tessitori, M., Cappelli, R., Poli, D., Quintavalla, R., Melone, F., Cosmi, F., Pizzini, A., Piseddu, G., Fanelli, R., Latella, C., Santi, R., Pancaldi, L., De Cristofaro, R., Palareti, G., De Blasio, A., Salerno Uriarte, J., Minetti, F., Pogliani, E. M., Lonati, L. M., Accogli, M., Ciampani, N., Malengo, S., Feola, M., Raisaro, A., Fattore, L., Grilli, P., Germini, F., Settimi, M., Alunni, M., Duranti, G., Tedeschi, L., Baglioni, G., Avanzino, G., Berardi, M., Pannacci, V., Giombolini, A., Nicoli, S., Scarponi, T., Allasia, B., Ricciarini, P., Nasorri, R., Argena, A., Bossolasco, P., Ronchini, P., Filippi, A., Tradati, F., Bulla, C., Donzelli, L., Foppa, L., Bottarelli, M. L., Tomasello, A., Mauric, A., Femiano, C., Reggio, R., Lillo, F., Mariani, A., Forcignanò, F., Volpe, M., D'Avino, M., Bongiorni, M. 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Subjects: Registrie, Male, Time Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, 030204 cardiovascular system & hematology, Electrocardiography, 0302 clinical medicine, Risk Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, India, Prevalence, Prognosis, Prospective Studies, Survival Rate, Thromboembolism, Registries, Risk Assessment, Medicine, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, Risk assessment, Human, medicine.medical_specialty, Time Factor, RD1-811, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Risk factor, Survival rate, Fibrillation, business.industry, Risk Factor, ta3121, medicine.disease, Clinical trial, Prospective Studie, RC666-701, Surgery, Clinical and Preventive Cardiology, business
Abstract: Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
Published: 2018
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16. Alterações do parênquima cerebral durante a senilidade em gatos domésticos

Author: Miriam Harumi Tsunemi, A. V. Klein, Viviam Rocco Babicsak, Luiz Carlos Vulcano, and Universidade Estadual Paulista (Unesp)
Subjects: Aging, Pathology, medicine.medical_specialty, neuroanatomy, 040301 veterinary sciences, senility, Normal aging, parenchymal changes, Senilidade, Senility, Parenchymal changes, 0403 veterinary science, 03 medical and health sciences, Magnetic resonance imaging, 0302 clinical medicine, Atrophy, Parenchyma, medicine, magnetic resonance imaging, Interthalamic adhesion, lcsh:Veterinary medicine, CATS, General Veterinary, medicine.diagnostic_test, business.industry, aging, cats, Brain, 04 agricultural and veterinary sciences, Neuroanatomia, Ressonância magnética, medicine.disease, Parênquima cerebral, Gatos, Neuroanatomy, medicine.anatomical_structure, Encéfalo, Cats, lcsh:SF600-1100, Cerebellar atrophy, business, 030217 neurology & neurosurgery
Abstract: Made available in DSpace on 2018-12-11T17:22:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01. Added 1 bitstream(s) on 2019-10-09T18:31:58Z : No. of bitstreams: 1 S0100-736X2018000601196.pdf: 972631 bytes, checksum: 136b09fbf4352b4105a9385f46ca3445 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This study aimed to identify changes related to brain parenchyma as advancing age in healthy domestic cats. Our hypothesis is that cats suffer cerebral and cerebellar atrophy and show focal changes in signal intensity of the brain parenchyma in accordance with the progression of age. Twelve adult (1 to 6 years), eleven mature (7 to11 years) and ten geriatric non-brachycephalic cats (12 years or more of age) underwent brain magnetic resonance imaging (MRI). There were no changes in signal intensity and contrast uptake in brain parenchyma of the cats. Geriatric animals showed significantly lower average thickness of the interthalamic adhesion and percentage of the cerebral parenchyma volume in relation to intracranial volume than those found in the adult group. No significant differences were found between groups for cerebral volume, cerebellar volume and percentage of cerebellar volume in relation to intracranial volume. The results of this study indicate that atrophy of the cerebral parenchyma, including the interthalamic adhesion, occurs with age in domestic cats, confirming the hypothesis of the study. However, the results did not corroborate the hypothesis that cats show cerebellar atrophy and focal changes in signal intensity of the brain parenchyma with advancing age. Este estudo objetivou a identificação de alterações no parênquima cerebral relacionadas ao avanço da idade em gatos domésticos saudáveis. Nossa hipótese é de que os gatos sofrem atrofia cerebral e cerebelar, além de alterações focais na intensidade do sinal do parênquima cerebral, de acordo com a progressão da idade. Doze gatos não braquicéfalos adultos (1 a 6 anos), onze maduros (7 a 11 anos) e dez geriátricos (12 anos ou mais) foram submetidos à ressonância magnética encefálica. Não foram observadas alterações na intensidade do sinal e na captação de contraste do parênquima encefálico nos gatos. Os animais geriátricos apresentaram médias da espessura da adesão intertalâmica e porcentagem do volume do parênquima cerebral, em relação ao volume intracraniano, significativamente menores a aquelas encontradas no grupo dos adultos. Não foram encontradas diferenças significativas entre os grupos para volume cerebral, volume cerebelar e porcentagem de volume cerebelar em relação ao volume intracraniano. Os resultados deste estudo indicam que a atrofia do parênquima cerebral, incluindo a adesão intertalâmica, ocorre com o avanço da idade em gatos domésticos, confirmando a hipótese do estudo. No entanto, os resultados não corroboraram a hipótese de que os gatos apresentam atrofia cerebelar e alterações focais na intensidade do sinal do parênquima encefálico com a progressão da idade. Departamento de Reprodução Animal e Radiologia Veterinária Faculdade de Medicina Veterinária e Zootecnia (FMVZ) Universidade Estadual Paulista (Unesp) Campus de Botucatu, Rua Prof. Dr. Walter Mauricio Correa s/n Departamento de Bioestatística Instituto de Biociências Universidade Estadual Paulista (Unesp) Campus de Botucatu, Rua Prof. Dr. Walter Mauricio Correa s/n Departamento de Reprodução Animal e Radiologia Veterinária Faculdade de Medicina Veterinária e Zootecnia (FMVZ) Universidade Estadual Paulista (Unesp) Campus de Botucatu, Rua Prof. Dr. Walter Mauricio Correa s/n Departamento de Bioestatística Instituto de Biociências Universidade Estadual Paulista (Unesp) Campus de Botucatu, Rua Prof. Dr. Walter Mauricio Correa s/n FAPESP: 2013/06148-0
Published: 2018
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17. Explosion‐Generated Infrasound Recorded on Ground and Airborne Microbarometers at Regional Distances

Author: Jonathan Lees, C. Ballard, Eliot F. Young, V. Klein, Stephen J. Arrowsmith, and Daniel C. Bowman
Subjects: Geophysics, 010504 meteorology & atmospheric sciences, Infrasound, Environmental science, 010502 geochemistry & geophysics, 01 natural sciences, Seismology, 0105 earth and related environmental sciences
Published: 2018
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18. Membrane-based sample inlet for centrifugal microfluidic cartridges

Author: Roland Zengerle, Sebastian Hin, Mark Keller, F. von Stetten, M. Loskyll, Konstantinos Mitsakakis, V. Klein, and Oliver Strohmeier
Subjects: Analyte, Chromatography, Materials science, Capillary action, 010401 analytical chemistry, Microfluidics, Pipette, 02 engineering and technology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Cartridge, Blood plasma, Laboratory centrifuge, Electrical and Electronic Engineering, 0210 nano-technology, Whole blood
Abstract: Centrifugal microfluidics enables the rapid execution of complex blood sample analyses in a fully automated manner at the point of care. However, during blood sample addition, the cartridge is at rest and centrifugal forces are not present to allocate the sample in a controlled way. We present a versatile approach for the user-friendly, well-controlled and safe sample addition into a centrifugal microfluidic cartridge for use in serology. It features a commercial (plasma separation) membrane stacked into the inlet chamber of the cartridge. This combination of sample inlet and plasma separation in one structural unit brings the advantage of reducing footprint in highly integrated point-of-care testing. By using a pipette the user may add a blood sample (90 μL) to the membrane holding the liquid by capillary forces. Flowing across the membrane, cells separate from blood plasma. The blood plasma releases into the downstream structure upon centrifugation. The mean plasma recovery rate was 57.3 (± 4.7) % and mean plasma purity 99.5 (± 0.6) % from samples of varying hematocrit (36%–59%). Furthermore, the analyte C-reactive protein (CRP) did not significantly adsorb to the membrane. This was concluded, since CRP immunoassay results with plasma from spiked whole blood, obtained from membrane-based plasma separation and from plasma separation on a standard laboratory centrifuge, did not significantly differ. Thus, the suggested approach is promising for simultaneous application as sample inlet holding the sample by capillary forces and as a plasma separation module for centrifugal microfluidics. Potential future applications may include other sample matrices. The use with further blood transfer devices (capillary, directly from fingertip) seems possible, yet requiring further evaluation.
Published: 2018
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19. Effects of cuff size and position on the agreement between arterial blood pressure measured by Doppler ultrasound and through a dorsal pedal artery catheter in anesthetized cats

Author: Natache A. Garofalo, Eutálio Lm. Pimenta, A. V. Klein, Sofia A. Cerejo, Francisco J. Teixeira-Neto, Felipe S. Zanuzzo, Universidade Estadual Paulista (Unesp), and Universidade Federal de Minas Gerais (UFMG)
Subjects: Male, Mean arterial pressure, 040301 veterinary sciences, Tarsus (eyelids), Blood Pressure, 0403 veterinary science, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Catheterization, Peripheral, Medicine, Animals, noninvasive blood pressure, General Veterinary, business.industry, cats, Doppler, Ultrasonography, Doppler, 04 agricultural and veterinary sciences, Circumference, Blood Pressure Monitors, Catheter, Neutering, medicine.anatomical_structure, Blood pressure, Isoflurane, Anesthesia, Cuff, Cats, Female, business, medicine.drug
Abstract: Made available in DSpace on 2020-12-12T01:13:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: To compare the effects of cuff size/position on the agreement between arterial blood pressure measured by Doppler ultrasound (ABPDoppler) and dorsal pedal artery catheter measurements of systolic (SAPinvasive) and mean arterial pressure (MAPinvasive) in anesthetized cats. Study design: Prospective study. Animals: A total of eight cats (3.0–3.8 kg) for neutering. Methods: During isoflurane anesthesia, before surgery, changes in end-tidal isoflurane concentrations and/or administration of dopamine were performed to achieve SAPinvasive within 60–150 mmHg. Cuff sizes 1, 2 and 3 (bladder width: 20, 25 and 35 mm, respectively) were placed on distal third of the antebrachium, above the tarsus and below the tarsus for ABPDoppler measurements. Agreement between ABPDoppler and SAPinvasive or between ABPDoppler and MAPinvasive was compared with reference standards for noninvasive blood pressure devices used in humans and small animals. Results: Mean bias and precision (±standard deviation) between ABPDoppler and SAPinvasive met veterinary standards (≤10 ± 15 mmHg), but not human standards (≤5 ± 8 mmHg), with cuffs 1 and 2 placed on the thoracic limb (7.4 ± 13.9 and –5.8 ± 9.5 mmHg, respectively), and with cuff 2 placed proximal to the tarsus (7.2 ± 12.4 mmHg). Cuff width-to-limb circumference ratios resulting in acceptable agreement between ABPDoppler and SAPinvasive were 0.31 ± 0.04 (cuff 1) and 0.42 ± 0.05 (cuff 2) on the thoracic limb, and 0.43 ± 0.05 (cuff 2) above the tarsus. ABPDoppler showed no acceptable agreement with MAPinvasive by any reference standard. Conclusions and clinical relevance: The agreement between ABPDoppler and SAPinvasive can be optimized by placing the occlusive cuff on the distal third of the antebrachium and above the tarsus. In these locations, cuff width should approach 40% of limb circumference to provide clinically acceptable estimations of SAPinvasive. Doppler ultrasound cannot be used to estimate MAPinvasive in cats. Faculdade de Medicina Veterinária e Zootecnia Universidade Estadual Paulista (UNESP) Escola de Veterinária Universidade Federal de Minas Gerais (UFMG) Faculdade de Medicina Veterinária e Zootecnia Universidade Estadual Paulista (UNESP) FAPESP: 2012/09837-8
Published: 2019

20. One-step, wash-free, bead-based immunoassay employing bound-free phase detection

Author: Michal Karpisek, Konstantinos Mitsakakis, V. Klein, Benita Johannsen, Roland Zengerle, Susanna M. Früh, Nagihan Bostanci, Nils Paust, and Desirée Baumgartner
Subjects: Analyte, Point-of-Care Systems, One-Step, 02 engineering and technology, 01 natural sciences, Biochemistry, Analytical Chemistry, Limit of Detection, medicine, Environmental Chemistry, Spectroscopy, Immunoassay, Detection limit, Reproducibility, Chromatography, medicine.diagnostic_test, Chemistry, 010401 analytical chemistry, Reproducibility of Results, 021001 nanoscience & nanotechnology, Fluorescence, 0104 chemical sciences, C-Reactive Protein, Certified reference materials, Reagent, 0210 nano-technology
Abstract: We present a simple and fast one-step heterogeneous immunoassay, with performance characteristics that can enable easy and versatile adaptation to miniaturized, automated point-of-care systems. This novel analytical method uses magnetic and fluorescent beads as capture and detection agents respectively. Its main feature is the measurement of the fluorescent signal in the bound-free phase for (semi-)quantitative detection of analytes. Thus, no washing is required and the workflow consists only of sample and reagent supply, incubation, separation and detection. The immunoassay concept is demonstrated with C-reactive protein (CRP), a systemic inflammation marker. CRP in only 5 μL of undiluted serum was measured in the range 20–140 mg L−1 (includes clinically relevant cut-off values). The limit of detection (LOD) was 22.1 ± 6.3 mg L−1 (incubation 15 min). A CRP certified reference material was measured on five different days. Intra- and inter-assay coefficients of variation were 4.6 ± 1.9% and 5.6% respectively. To demonstrate the compatibility of the assay concept with additional matrices and concentration ranges, three oral inflammation markers, namely matrix metalloproteinases 8 and 9 (MMP-8, MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1), were measured in saliva in the ranges 0.47–30 ng mL−1 for MMP-8 and MMP-9, and 0.69–44 ng mL−1 for TIMP-1. LODs were 0.24 ng mL−1, 0.38 ng mL−1 and 0.39 ng mL−1 respectively (incubation 20 min). Multiplexing capacity of the assay concept was also shown with these markers. The demonstrated excellent reproducibility of the results, combined with the versatility and low complexity of the introduced immunoassay concept, make it an attractive candidate for applied analytical chemistry and automated point-of-care testing.
Published: 2021
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21. C-reactive protein and interleukin 6 microfluidic immunoassays with on-chip pre-stored reagents and centrifugo-pneumatic liquid control

Author: Y. Zhao, V. Klein, Nils Paust, Gregor Czilwik, Roland Zengerle, and Konstantinos Mitsakakis
Subjects: Microfluidics, Biomedical Engineering, Bioengineering, 02 engineering and technology, 01 natural sciences, Biochemistry, Buffer (optical fiber), Limit of Detection, Lab-On-A-Chip Devices, Humans, Spinning, Immunoassay, Detection limit, Range (particle radiation), Chromatography, Interleukin-6, Chemistry, 010401 analytical chemistry, Reproducibility of Results, Substrate (chemistry), Equipment Design, General Chemistry, Microfluidic Analytical Techniques, 021001 nanoscience & nanotechnology, 0104 chemical sciences, C-Reactive Protein, Reagent, Linear Models, Particle, 0210 nano-technology
Abstract: We present a fully automated centrifugal microfluidic method for particle based protein immunoassays. Stick-pack technology is employed for pre-storage and release of liquid reagents. Quantitative layout of centrifugo-pneumatic particle handling, including timed valving, switching and pumping is assisted by network simulations. The automation is exclusively controlled by the spinning frequency and does not require any additional means. New centrifugal microfluidic process chains are developed in order to sequentially supply wash buffer based on frequency dependent stick-pack opening and pneumatic pumping to perform two washing steps from one stored wash buffer; pre-store and re-suspend functionalized microparticles on a disk; and switch between the path of the waste fluid and the path of the substrate reaction product with 100% efficiency. The automated immunoassay concept is composed of on demand ligand binding, two washing steps, the substrate reaction, timed separation of the reaction products, and termination of the substrate reaction. We demonstrated separation of particles from three different liquids with particle loss below 4% and residual liquid remaining within particles below 3%. The automated immunoassay concept was demonstrated by means of detecting C-reactive protein (CRP) in the range of 1–81 ng ml−1 and interleukin 6 (IL-6) in the range of 64–13500 pg ml−1. The limit of detection and quantification were 1.0 ng ml−1 and 2.1 ng ml−1 for CRP and 64 pg ml−1 and 205 pg ml−1 for IL-6, respectively.
Published: 2017
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22. Changes in pulse pressure variation and plethysmographic variability index caused by hypotension-inducing hemorrhage followed by volume replacement in isoflurane-anesthetized dogs

Author: A. Lagos-Carvajal, M. S. Diniz, A. V. Klein, Francisco J. Teixeira-Neto, Diana Rocío Becerra-Velásquez, and Natache A. Garofalo
Subjects: Mean arterial pressure, 040301 veterinary sciences, Hypovolemia, Autologous blood, Volume replacement, Blood Pressure, 0403 veterinary science, 03 medical and health sciences, Dogs, 0302 clinical medicine, 030202 anesthesiology, medicine, Animals, Plethysmograph, Anesthesia, Infusions, Intravenous, Stroke, Isoflurane, General Veterinary, business.industry, Hemodynamics, 04 agricultural and veterinary sciences, General Medicine, medicine.disease, Pulse pressure, Blood pressure, Anesthesia Recovery Period, Anesthetics, Inhalation, business, medicine.drug
Abstract: OBJECTIVE To compare changes in pulse pressure variation (PPV) and plethysmographic variability index (PVI) induced by hemorrhage followed by volume replacement (VR) in isoflurane-anesthetized dogs. ANIMALS 7 healthy adult dogs. PROCEDURE Each dog was anesthetized with isoflurane and mechanically ventilated. End-tidal isoflurane concentration was adjusted to maintain mean arterial pressure (MAP) at 60 to 70 mm Hg before hemorrhage. Controlled hemorrhage was initiated and continued until the MAP decreased to 40 to 50 mm Hg, then autologous blood removed during hemorrhage was retransfused during VR. Various physiologic variables including PPV and PVI were recorded immediately before (baseline) and after controlled hemorrhage and immediately after VR. RESULTS Mean ± SD PPV and PVI were significantly increased from baseline after hemorrhage (PPV, 20 ± 6%; PVI, 18 ± 4%). After VR, the mean PPV (7 ± 3%) returned to a value similar to baseline, whereas the mean PVI (10 ± 3%) was significantly lower than that at baseline. Cardiac index (CI) and stroke index (SI) were significantly decreased from baseline after hemorrhage (CI, 2.07 ± 0.26 L/min/m2; SI, 20 ± 3 mL/beat/m2) and returned to values similar to baseline after VR (CI, 4.25 ± 0.63 L/min/m2; SI, 36 ± 6 mL/beat/m2). There was a significant positive correlation (r2 = 0.77) between PPV and PVI after hemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that both PPV and PVI may be useful for identification of dogs that respond to VR with increases in SI and CI (ie, dogs in the preload-dependent limb of the Frank-Starling curve).
Published: 2016
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23. Convection and diffusion assisted reactive coupling at incompatible semi-crystalline polymer interfaces

Author: T Barraud, H Hervet, Christophe Poulard, D Brunello, Frédéric Restagno, Liliane Léger, S. Devisme, and V Klein
Subjects: chemistry.chemical_classification, Coupling (electronics), Convection, Materials science, chemistry, Chemical physics, Diffusion, Copolymer, General Materials Science, Polymer, Condensed Matter Physics, Atomic and Molecular Physics, and Optics
Abstract: Based on a specifically designed stretching apparatus, we study the incidence of the stretching parameters on the formation of polypropylene-polyamide-6 (PP-PA6) copolymers acting as adhesion promoters in PP/PA6 multilayer films. The stretching apparatus mimics the stretching conditions found in the air gap of a co-extrusion machine in terms of stretching velocities and distances and of cooling rates. We propose a simplified numerical modeling of these experiments. It allows to explore how the various molecular (concentration in reactive species, diffusion coefficient) and stretching parameters affect the time evolution of the copolymer surface density during stretching. More precisely, we show that even though the contact time for the reaction is large regarding the reaction time, a dilation of the surface can result in a strong lowering of the grafting density at the interface.
Published: 2020
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24. Ultramorfologic spetialities in the placenta at the powerless labour

Author: A. V. Klein, L.G. Tulakina, N.M. Milyaeva, S.V. Pichugova, Y.B. Beykin, and V.V. Kovalev
Subjects: medicine.medical_specialty, medicine.anatomical_structure, Obstetrics, business.industry, Placenta, medicine, business
Published: 2016
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25. EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from 'ERBITUX-OUEST'

Author: Corinne Alleaume, F. Grude, Arnaud Uguen, Nacr Eddine Achour, Daniel Ten Martin, Gilles Lemasson, A. Volant, Joseph Politis, Olivier Capitain, Claire Stampfli, Laurent Miglianico, Jérome Chettrit, Jean-François Ramée, Philippe Deguiral, Véronique Verriele, Claire Magois, Norbert Padilla, Annie Wdowik, Sophie Michalak, Murielle Broyer-Petit, Erick Gamelin, Pierre-Luc Etienne, Pierre Marie Girardot, Jean-Philippe Metges, Jean-Jacques Auger, Christian Laboisse, Roger Faroux, Serge Eloit, V. Klein, Fanny Marhuenda, A. Gourlaouen, Marie-Aude Coulon, Delphine Deniel Lagadec, Isabelle Cumin, Louis-Rémi De Ybarlucea, Christian Riche, Bruno Turlin, Olivier Dupuis, Alain Bargain, Eric Lavoine, Ludovic Rosenfeld, Alain Penchet, Jean-Luc Raoul, Jean-Yves Douillard, Viorel Vasiliu, Nathalie Heresbach, Yann Touchefeu, Karine Bideau, and Frédéric Staroz
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, biology, Cetuximab, business.industry, Colorectal cancer, medicine.disease, digestive system diseases, Egfr expression, Oxaliplatin, Irinotecan, 03 medical and health sciences, Regimen, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, biology.protein, Immunohistochemistry, Epidermal growth factor receptor, business, medicine.drug
Abstract: Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.
Published: 2016
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26. Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Author: Diana Rocío Becerra-Velásquez, A. V. Klein, Carlos A. Dias-Junior, M. S. Diniz, Angie Paola Lagos-Carvajal, Thalita Leone Alves Rocha, and Francisco J. Teixeira-Neto
Subjects: Male, medicine.medical_specialty, Hypertension, Pulmonary, Vasodilator Agents, Cardiac index, Vasodilation, General Biochemistry, Genetics and Molecular Biology, Adrenomedullin, Internal medicine, Cyclic AMP, medicine, Animals, General Pharmacology, Toxicology and Pharmaceutics, Cyclic GMP, Lung, Sheep, business.industry, General Medicine, medicine.disease, Pulmonary hypertension, Pulmonary embolism, Disease Models, Animal, medicine.anatomical_structure, Endocrinology, Acute Disease, Vascular resistance, Pulmonary shunt, medicine.symptom, Pulmonary Embolism, business, hormones, hormone substitutes, and hormone antagonists
Abstract: The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE.Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 per group): animals not subjected to any intervention (Sham), animals with APE induced by microspheres (500 mg, intravenously) treated 30 min later by intravenous physiological saline (Emb group) or intravenous adrenomedullin (50 ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme immunoassay.Variables did not change over time in sham animals. In both embolized groups, microsphere injection significantly (P0.05) increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly increased cardiac index (22%-25%) from values recorded 30 min after APE (E30), without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%) and systemic vascular resistance index (32%-40%). Embolization significantly increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient, and pulmonary shunt fraction from baseline, but these variables were unaffected by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP levels were unaltered.Adrenomedullin induces systemic and pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying the gas exchange impairment associated with APE. The pulmonary anti-hypertensive effect of adrenomedullin may be offset by increases in cardiac index.
Published: 2015
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27. Health Canada’s perspective on the clinical development of biosimilars and related scientific and regulatory challenges

Author: Agnes V Klein, Jian Wang, and Ally Pen
Subjects: Drug Guides, Political science, Perspective (graphical), Biosimilar, Engineering ethics, Pharmacy
Published: 2015
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28. Magnetic chemiluminescent immunoassay for human C-reactive protein on the centrifugal microfluidics platform

Author: V. Klein, Roland Zengerle, Daniel Mark, A. Buderer, Günter Roth, Gregor Czilwik, Sandeep Kumar Vashist, and F. von Stetten
Subjects: Detection limit, High sensitivity crp, Chromatography, medicine.diagnostic_test, Chemistry, General Chemical Engineering, Microfluidics, General Chemistry, Centrifugal microfluidics, Clinical Practice, Chemiluminescent immunoassay, Immunoassay, medicine, Inflammatory biomarker
Abstract: Human C-reactive protein (CRP) has been reported as an inflammatory biomarker with the highest reference for use in clinical practice. However, the existing analytical techniques are lacking automation and simplicity, as desired for a prospective immunoassay format for point-of-care (PoC) analysis. We have developed an automated magnetic chemiluminescent immunoassay (MCIA) on a mobile analyser for rapid PoC determination of CRP. The MCIA is fully automated after the initial loading of sample and immunoreagents at the inlet ports. The automated protocol involves the transportation of magnetic capture microparticles between adjacent reaction compartments using a set of stationary magnets, a microfluidic polymer disposable and a specific centrifugal protocol. The developed MCIA has a sample-to-answer time of 25 min and hands-on time of approximately 5 min. It detects the entire pathophysiological range of CRP, as desired for clinically-relevant high sensitivity CRP immunoassay format, i.e. 3–81 ng mL−1 in diluted human serum with a limit of detection (LOD) and limit of quantification (LOQ) of 1.5 ng mL−1 and 1.8 ng mL−1, respectively.
Published: 2015
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29. Extrapolation of Indications for Biosimilars

Author: Catherine Njue, Jian Wang, Wallace Lauzon, and Agnes V. Klein
Subjects: business.industry, Extrapolation, Medicine, Applied mathematics, Biosimilar, business
Published: 2017
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30. An Environmental Scan of Academic Emergency Medicine at the 17 Canadian Medical Schools: Why Does this Matter to Emergency Physicians? - CORRIGENDUM

Author: G. Stiell, J. D. Artz, E. S. Lang, J. Sherbino, L. J. Morrison, J. Christenson, J. J. Perry, C. Topping, R. Woods, R. S. Green, R. Lim, K. Magee, J. Foote, G. Meckle, M. Mensour, S. Field, B. Chung, M. Kuuskne, J. Ducharme, V. Klein, and J. McEwen
Subjects: Emergency Medicine
Published: 2017

31. Detox diets for toxin elimination and weight management: a critical review of the evidence

Author: A. V. Klein and Hosen Kiat
Subjects: Nutrition and Dietetics, Olestra, business.industry, medicine.medical_treatment, Medicine (miscellaneous), Small sample, Diet, Toxicology, Liver detoxification, Weight loss, Clinical evidence, Environmental health, Detoxification, Weight Loss, Weight management, medicine, Animals, Humans, Obesity, medicine.symptom, business, Dieting
Abstract: Detox diets are popular dieting strategies that claim to facilitate toxin elimination and weight loss, thereby promoting health and well-being. The present review examines whether detox diets are necessary, what they involve, whether they are effective and whether they present any dangers. Although the detox industry is booming, there is very little clinical evidence to support the use of these diets. A handful of clinical studies have shown that commercial detox diets enhance liver detoxification and eliminate persistent organic pollutants from the body, although these studies are hampered by flawed methodologies and small sample sizes. There is preliminary evidence to suggest that certain foods such as coriander, nori and olestra have detoxification properties, although the majority of these studies have been performed in animals. To the best of our knowledge, no randomised controlled trials have been conducted to assess the effectiveness of commercial detox diets in humans. This is an area that deserves attention so that consumers can be informed of the potential benefits and risks of detox programmes.
Published: 2014
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32. Effects of dexmedetomidine on pulse pressure variation changes induced by hemorrhage followed by volume replacement in isoflurane-anesthetized dogs

Author: M. S. Diniz, Felipe S. Zanuzzo, Paulo do Nascimento, A. V. Klein, Francisco J. Teixeira-Neto, L. R. Teixeira, and Thaísa D. Cândido
Subjects: Minimum alveolar concentration, Mean arterial pressure, General Veterinary, business.industry, Blood volume, Pulse pressure, medicine.anatomical_structure, Hypovolemia, Anesthesia, Vascular resistance, Medicine, medicine.symptom, Dexmedetomidine, business, Tidal volume, medicine.drug
Abstract: Objectives To evaluate the effects of dexmedetomidine (DEX) on changes in pulse pressure variation (PPV) induced by hemorrhage followed by volume replacement (VR) during isoflurane (ISO) anesthesia. Design Prospective, randomized, crossover study. Setting Research laboratory at a veterinary teaching hospital. Animals Eight adult dogs. Interventions Anesthesia was maintained with 1.3 times the minimum alveolar concentration (MAC) of ISO alone or ISO with DEX (ISO-DEX, 1.6 μg/kg [bolus], followed by 2 μg/kg/h). Atropine was administered 30 minutes prior to hemorrhage in the ISO-DEX treatment. Ventilation was controlled (tidal volume of 12 mL/kg, positive end-expiratory pressure of 7 cm H2O, respiratory rate of 16–20/min) under neuromuscular blockade. After recording baseline data, progressive withdrawal of 10%, 20%, and 30% of blood volume (HV10, HV20, and HV30, respectively [measurements during hemorrhage, indicating x% of blood volume removed]) was followed by VR with autologous blood. Measurements and Main Results In 4 of 8 ISO dogs, hemorrhage decreased mean arterial pressure (MAP) < 60 mm Hg. Based on mean arterial pressure after hemorrhage, dogs were assigned to hypotensive (HG) and normotensive (NG) groups post hoc. During ISO, stroke index and cardiac index decreased with hemorrhage (P < 0.05), while VR normalized or increased these variables. The PPV (%, mean [range]) was increased by hemorrhage from 7 (5–9) to 20 (12–27) and 27 (17–40) at HV20 and HV30, respectively, only in ISO dogs in the HG; PPV returned to baseline after VR. Dexmedetomidine caused increases in systemic vascular resistance (in dogs in HG and NG), and prevented the increase in PPV with hemorrhage. Conclusions During ISO anesthesia, PPV increases in individuals prone to developing hypotension from hypovolemia. Because DEX prevents the increase in PPV associated with hypovolemia, PPV should not be used to guide VR in dogs that have been given DEX.
Published: 2014
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33. Subsequent entry biologics (biosimilars) in Canada: approaches to interchangeability and the extrapolation of indications and uses

Author: Jian Wang, Patrick Bedford, and Agnes V Klein
Subjects: Risk analysis (engineering), Operations research, business.industry, Drug Guides, Extrapolation, Medicine, Biosimilar, Pharmacy, business, Interchangeability
Published: 2014
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34. Biosimilar monoclonal antibodies: A Canadian regulatory perspective on the assessment of clinically relevant differences and indication extrapolation

Author: Agnes V. Klein, Jian Wang, and Bradley J. Scott
Subjects: Pharmacology, Canada, medicine.medical_specialty, medicine.drug_class, business.industry, Authorization, Antibodies, Monoclonal, Biosimilar, Monoclonal antibody, Biotechnology, Clinical trial, Reference product, Therapeutic Equivalency, Family medicine, Product Surveillance, Postmarketing, medicine, Humans, Pharmacology (medical), Product (category theory), business, Biosimilar Pharmaceuticals, Drug Approval
Abstract: Monoclonal antibodies have become mainstays of treatment for many diseases. After more than a decade on the Canadian market, a number of authorized monoclonal antibody products are facing patent expiry. Given their success, most notably in the areas of oncology and autoimmune disease, pharmaceutical and biotechnology companies are eager to produce their own biosimilar versions and have begun manufacturing and testing for a variety of monoclonal antibody products. In October of 2013, the first biosimilar monoclonal antibody products were approved by the European Medicines Agency (Remsima™ and Inflectra™). These products were authorized by Health Canada shortly after; however, while the EMA allowed for extrapolation to all of the indications held by the reference product, Health Canada limited extrapolation to a subset of the indications held by the reference product, Remicade®. The purpose of this review is to discuss the Canadian regulatory framework for the authorization of biosimilar mAbs with specific discussion around the clinical requirements for establishing (bio)-similarity and to present the principles that are used in the clinical assessment of New Drug Submissions for intended biosimilar monoclonal antibodies. Health Canada's current views regarding indication extrapolation, product interchangeability, and post-market surveillance are discussed as well.
Published: 2014
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35. Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics

Author: C. Riche, J. F. Bouret, N. A. Achour, M. I. Labarre, L. Derenne, A. Ulvoas, D. Martin, Hugues Bourgeois, P. Leynia, T. Matysiak Budnik, G. Piriou, P. L. Etienne, A. M. Vidal, V. Rossi, P. Michel Langlet, D. Déniel Lagadec, Marc Porneuf, M. N. Julien, Olivier Capitain, C. Chouzenoux, E. Jobard, C. Naveau Ploux, Isabelle Cumin, Olivier Dupuis, Loïc Campion, Claire Stampfli, Jean-Yves Douillard, Erick Gamelin, C. Bertrand, A. Brouard, L. Guivarch, V. Guérin Meyer, E. Peguet, Fanny Marhuenda, E. Boucher, Jean-Philippe Metges, L. Miglianico, S. Roussel, A. S. Le Bris Michel, F. Royet, J. Faycal, A. Gourlaouen, P. Thomaré, D. Grasset, F. Riaud, C. Louvigné, Hélène Senellart, S. Barré, S. Rochard, M. Couturier, Oana Cojocarasu, S. Gouva, H. Desclos, J. Egreteau, C. Bertholom, C. Bodin, M. A. Lebot, Jean-Luc Raoul, G. Le Bihan, V. Bicheler, V. Klein, F. Grude, C. Elhannani, R. Largeau, Philippe Deguiral, Roger Faroux, F. Suberville, B. Person, R. Bessard, C. Grollier, E. Crespeau, and Jean-François Ramée
Subjects: Oncology
Abstract: En 2006, bevacizumab-FOLFIRI represente la therapie ciblee administrable des la premiere ligne chez les patients porteurs d’un cancer colorectal metastatique non operable. Une serie homogene de 111 patients colliges en region Bretagne et Pays de la Loire ayant recu du bevacizumab- FOLFIRI en premiere ligne en 2006 revele les resultats suivants: 51 reponses, 29 stabilites, 21 progressions et 10 toxicites avant evaluation. La mediane de survie globale (OS) est de 25,1 mois et la mediane de survie sans progression (PFS) de 10,2 mois. Dans le cas d’une chirurgie secondaire, l’OS median triple de 18,8 mois chez les patients non reseques versus 59,2 mois ceux reseques. En comparant les sujets âges de plus et de moins de 70 ans, aucune difference n’a ete mise en evidence en termes de benefice ou de risque. Bevacizumab-FOLFIRI pourrait etre administre en pratique courante chez les personnes âgees sous couvert d’une evaluation geriatrique et d’une approche multidisciplinaire.
Published: 2014
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36. Perspectives temporelles et satisfaction de vie chez les personnes âgées : test de l’effet médiateur du sentiment d’auto-efficacité

Author: Raphaël Trouillet, Kamel Gana, V. Klein, and Yaël Saada
Subjects: 05 social sciences, 050109 social psychology, 0501 psychology and cognitive sciences, 050105 experimental psychology, Applied Psychology
Abstract: Resume L’objectif de cette recherche etait d’etudier les liens entre les perspectives temporelles telles que definies par Zimbardo et Boyd (1999) et la satisfaction de vie aupres d’un echantillon de personnes âgees (n = 188). Nous faisions l’hypothese que ces liens seraient mediatises par le sentiment d’auto-efficacite generalisee. Pour ce faire, un modele en pistes causales assorti d’une procedure de reechantillonnage fut teste. L’âge, le sexe, la sante subjective et l’humeur depressive y etaient introduites comme variables de controle. Nos resultats ont revele que : seul le present hedoniste exerce un effet indirect positif sur la satisfaction de vie a travers le sentiment d’auto-efficacite ; le passe negatif semble exercer un effet negatif aussi bien direct qu’indirect sur la satisfaction de vie ; le present fataliste exerce un effet negatif exclusivement direct sur la satisfaction de vie ; ni le passe positif ni le futur n’exercent un quelconque effet sur la satisfaction de vie. Ces resultats ainsi que leurs limites ont fait l’objet d’une discussion.
Published: 2013
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37. Facile Preparation of Mono-, Di- and Mixed-Carboxylato Platinum(IV) Complexes for Versatile Anticancer Prodrug Design

Author: Dan Gibson, Ezequiel Wexselblatt, Alice V. Klein, Yousef Najajreh, Trevor W. Hambley, Paul D. Bonnitcha, and Jenny Z. Zhang
Subjects: Molecular Structure, Organoplatinum Compounds, Organic Chemistry, chemistry.chemical_element, Antineoplastic Agents, General Chemistry, Peroxide, Combinatorial chemistry, Catalysis, chemistry.chemical_compound, chemistry, Carboxylation, Drug Design, Molecule, Organic chemistry, Prodrugs, Carboxylate, Azide, Pendant group, Platinum, Oxidation-Reduction, Carbodiimide
Abstract: Facile strategies were developed for the versatile functionalization of platinum(IV) axial sites, allowing for easy accessibility to unsymmetric mono- and mixed-carboxylato, as well as symmetric di-substituted platinum(IV) complexes. The first method involves the direct oxidation and carboxylation of the platinum(II) center using an appropriate peroxide and the carboxylate of choice to firstly yield a monocarboxylato monohydroxido platinum(IV) complex. This platinum(IV) intermediate can undergo further carboxylation to give rise to a mixed-carboxylato platinum(IV) complex. The second method involves the activation of the carboxylate of choice by a common carbodiimide coupling reagent, and its reaction with a dihydroxido platinum(IV) precursor to give the monocarboxylato platinum(IV) complex. Uronium salts can be employed to promote efficient dicarboxylation of the dihydroxido platinum(IV) precursor. Lastly, an axial azide pendant group was demonstrated to be suitable for orthogonal "click" conjugation reactions.
Published: 2012
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38. Combined excision and intralesional bevacizumab for sebaceous carcinoma of the eyelid in an Amur tiger (Panthera tigris altaica)

Author: Lin V. Klein, Mary L. Utter, Kathryn L. Wotman, and Michele L. Edelmann
Subjects: medicine.medical_specialty, General Veterinary, Bevacizumab, Histology, Eyelid Neoplasm, Biology, medicine.disease, eye diseases, Surgery, Vascular endothelial growth factor, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, medicine, Histopathology, sense organs, Eyelid, Antiangiogenic drug, Sebaceous carcinoma, medicine.drug
Abstract: An 18-year-old zoo-kept female Amur tiger presented with an approximately 5 mm diameter lateral canthal eyelid mass in the left eye which grossly appeared red and irregular. The mass was completely excised via lateral canthoplasty. Histopathologic evaluation was consistent with a diagnosis of sebaceous cell carcinoma, which is a potentially aggressive cutaneous neoplasm. The sebaceous carcinoma recurred within 3 months and slowly increased in size until a second surgical excision was performed 9 months following the first surgery. The second surgical excision was combined with intralesional injection of 10 mg of the antiangiogenic drug bevacizumab. Histology confirmed the diagnosis. The tiger was euthanized 16 months postoperatively for reasons unrelated to, and without recurrence of, the eyelid neoplasm. At postmortem, no gross periocular or metastatic lesions were noted, and histopathology of the lateral canthus provided no evidence of recurrence. Surgical excision combined with intralesional bevacizumab treatment induced life-long resolution of the sebaceous carcinoma. Bevacizumab treatment may be associated with the regression of periocular angiogenic proliferative conditions, including neoplasia, by inhibiting angiogenesis.
Published: 2012
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39. Communication courte - Le rôle de l'insuline d'origine animale dans le traitement du diabète de type 1 et sa disponibilité

Author: E. Griffiths, Duc Vu, C. Legaré, A. V. Klein, and E. Taylor
Abstract: En raison d'un certain nombre de facteurs, on traite désormais davantage le diabète insulinodépendant au moyen de préparations d'insuline recombinante (biosynthétique) qu'au moyen d'insuline d'origine bovine et porcine. Cependant, certaines personnes atteintes du diabète de type 1 parviennent à mieux prendre leur diabète en charge à l'aide d'insuline d'origine animale. Malgré la disponibilité de plus en plus réduite de l'insuline d'origine animale et le déclin de sa production, on peut encore s'en procurer sur le marché canadien, en particulier l'insuline porcine. Cette communication décrit les mesures prises par Santé Canada relativement à la disponibilité de l'insuline d'origine animale.
Published: 2014
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40. Platinum Drug Distribution in Cancer Cells and Tumors

Author: Alice V. Klein and Trevor W. Hambley
Subjects: business.industry, MEDLINE, chemistry.chemical_element, Antineoplastic Agents, General Chemistry, Models, Biological, Text mining, chemistry, Neoplasms, Cancer cell, Cancer research, Animals, Humans, business, Platinum
Published: 2009
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41. Pathological manifestations of feline immunodeficiency virus (FIV) infection in wild African lions

Author: Jill Pecon-Slattery, Dahlem Smith, Paolo Martelli, Kathleen A. Alexander, Meredith A. Brown, Karthiyani Krishnasamy, Jennifer L. Troyer, Hanlie Evelyn Kathleen Winterbach, Stephen J. O'Brien, Christiaan W. Winterbach, Randall C. Johnson, Lin V. Klein, Melody E. Roelke, Graham Hemson, and Alfred L. Roca
Subjects: Lions, Male, Feline immunodeficiency virus, 040301 veterinary sciences, Lymphoid Tissue, Prevalence, Wild, Animals, Wild, Immunodeficiency Virus, Feline, Article, Serology, 0403 veterinary science, 03 medical and health sciences, Species Specificity, Free-ranging, Seroepidemiologic Studies, biology.animal, Virology, Pathology, Seroprevalence, Animals, 030304 developmental biology, Mouth neoplasm, 0303 health sciences, Botswana, biology, Papilloma, Lentivirus, virus diseases, Lentivirus Infections, 04 agricultural and veterinary sciences, biology.organism_classification, Gingivitis, FIV, Immune depletion, 3. Good health, Immunology, Female, Mouth Neoplasms, Panthera
Abstract: Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple-infected lions and anecdotal reports of lion morbidity associated with FIV seroprevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple-negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple-infected lions displayed a significant elevation in the prevalence of AIDS-defining conditions: lymphadenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters, depressed serum albumin, and elevated liver enzymes and gamma globulin. Spleen and lymph node biopsies from free-ranging FIVple-infected lions (N=9) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodeficiency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca).
Published: 2009
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42. Ultrastructural analysis application for spermatozoa study in male infertility

Author: A. V. Klein, L. G. Tulakina, S. V. Pichugova, and Beykin YaB
Subjects: Andrology, business.industry, Ultrastructure, Medicine, business, medicine.disease, Male infertility
Published: 2016
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43. Effects of Intrauterine Devices in Mares: A Histomorphological and Immunohistochemical Evaluation of the Endometrium

Author: V. Klein, K. Müller, Tiina Reilas, M. M. Rivera del Alamo, Terttu Katila, and Heinz-Adolf Schoon
Subjects: endocrine system, medicine.medical_specialty, 040301 veterinary sciences, Receptor expression, media_common.quotation_subject, Biopsy, Uterus, Luteal phase, Luteal Phase, Endometrium, 0403 veterinary science, Andrology, Endocrinology, Pregnancy, Internal medicine, medicine, Animals, Uteroglobin, Horses, Ovulation, reproductive and urinary physiology, Insemination, Artificial, media_common, medicine.diagnostic_test, biology, urogenital system, business.industry, Tartrate-Resistant Acid Phosphatase, 0402 animal and dairy science, 04 agricultural and veterinary sciences, 040201 dairy & animal science, Immunohistochemistry, Lipocalins, medicine.anatomical_structure, Ki-67 Antigen, Receptors, Estrogen, biology.protein, Animal Science and Zoology, Female, business, Receptors, Progesterone, Biotechnology, Endometrial biopsy, Intrauterine Devices
Abstract: Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and IUD-N groups, respectively. On Day 15 after ovulation, an endometrial biopsy was obtained to study histomorphological and immunohistochemical expression patterns of uterine proteins (uteroferrin, UF; uterocalin, UC; uteroglobin, UG), oestrogen and progesterone receptors (ER, PR), proliferation marker Ki-67 and content of inflammatory cells. Expression of UF was higher in IUD mares; the difference between pregnant and IUD-P mares was significant. Mares exhibiting a prolonged luteal phase (AI-P, IUD-P) showed only mild angiosclerosis and lower expression of both ER and PR than mares with a normal luteal phase (AI-N, IUD-N). No significant differences were detected in the numbers of inflammatory cells, with the exception of macrophages, which were more numerous in AI-P than AI-N mares. Although inflammatory cells were not detected in IUD mares, increased UF levels may indicate chronic inflammation. Young age and normality of the endometrial blood vessels may improve the efficacy of IUDs.
Published: 2015

44. Historical Development of Bromelain in the Treatment of Burn Wounds

Author: Gerold K. V. Klein
Subjects: Traditional medicine, Bromelain (pharmacology), business.industry, Medicine, business
Published: 2015
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45. Physicochemical Requirements Regarding Reacting Solutions for the Determination of Haemoglobin as Haemiglobincyanide

Author: A. v. Klein-Wisenberg
Published: 2015
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46. Electronic Raman Scattering from Superconductors in the Vortex State: Experimental Features and Theoretical Issues

Author: M. V. Klein
Subjects: Superconductivity, Superfluidity, Abrikosov vortex, Physics, Condensed matter physics, Condensed Matter::Superconductivity, Momentum transfer, Electron, Condensed Matter Physics, Vortex state, Electronic, Optical and Magnetic Materials, Magnetic field, Vortex
Abstract: In a superconductor, single-particle excitations created by adding or removing an electron require a minimum energy given by the absolute value | | of the superconducting energy gap . An applied magnetic field enters a type II superconductor in the form of Abrikosov vortices. Around the core of each vortex the super current flows with a circulation equal to h. For conventional superconductors the cores are believed to contain only “normal” metallic electrons. These potentially offer sources of damping for various excitations. The gap may depend on the wavevector k of the added or removed particle, and in the vortex state, on its position. Indeed, according to Ginzburg–Landau theory, is proportional to the superconducting order parameter, which acquires a position-dependent phase, the “winding phase,” that changes by 2π around any closed path that winds once around a vortex. In 1961, Abrikosov and Falkovskii [1] predicted that electronic Raman scattering at small momentum transfer from a clean BCS superconductor should reveal the gap as a discontinuous sharp rise to a peak at an energy transfer equal to twice the gap, i.e. at 2 . Sometimes referred to as a “pair-breaking peak,” the 2 feature results from the creation during the lightscattering process of an electron–hole pair, each part of which requires a minimum energy of [2]. Subsequent theoretical work was based on Greens function approaches. See [3–5] for examples. This paper presents a brief survey of the few experiments that probed the effect of a magnetic field
Published: 2006
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47. Resonance Raman study of 2Δ-gap like features in superconducting BI-2212 and YBCO

Author: D. A. Bonn, D. Budelmann, Walter Hardy, Michael Rübhausen, Benjamin L. Schulz, Miles V. Klein, Mark S. Williamsen, Prasenjit Guptasarma, and Ruixing Liang
Subjects: Superconductivity, Superconducting energy gap, Materials science, Condensed matter physics, Spectral weight, Doping, General Chemistry, Photon energy, Condensed Matter Physics, symbols.namesake, Nuclear magnetic resonance, symbols, General Materials Science, Raman spectroscopy
Abstract: We studied the variation of the 2 Δ -gap like peaks with incident photon energy E i in two superconducting samples, optimally doped YBCO ( T c =93.6 K) and overdoped Bi-2212 ( T c =82 K). Our results highlight the composite nature of the 2 Δ -gap like peaks in the HTS. Below the superconducting T c we see a redistribution of spectral weight and the appearance of the 2 Δ -gap like features. In B 1 g Raman symmetry these features change their shape, peak position, and intensity with increasing E i . For E i ∼3.5 eV we find little redistribution, only a strong new peak at a Raman frequency well above the accepted values of twice Δ max .
Published: 2006
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48. Resonance Raman study of the phonon spectra in superconducting Bi-2212 and Y-123

Author: Miles V. Klein, M.S. Williamsen, Prasenjit Guptasarma, Michael Rübhausen, Benjamin L. Schulz, Ruixing Liang, D. Bonn, D. Budelmann, and Walter Hardy
Subjects: Superconductivity, Condensed matter physics, Phonon, Chemistry, Doping, Analytical chemistry, Resonance, General Chemistry, Photon energy, Condensed Matter Physics, Zero-phonon line and phonon sideband, symbols.namesake, Condensed Matter::Superconductivity, symbols, Condensed Matter::Strongly Correlated Electrons, General Materials Science, Cuprate, Raman spectroscopy
Abstract: We studied the variation of phonon spectra with incident photon energy E i in two superconducting samples, optimally doped YBCO ( T c =93.6 K) and overdoped Bi-2212 ( T c =82 K). Our results highlight the layered nature of the cuprates. Especially the buffer layers that are thought to be responsible for the doping of the CuO 2 planes show complex phonon spectra. In Bi-2212 we find an activation of up to 13 phonon modes for a resonance that allows transitions into the Bi–O layers at 3.8 eV. For Y-123 we find also an activation of phonon modes as well as a huge matrix element when transitions into the chains at around 4.1 eV are possible. We also investigate the variation of the line shape of the O(II)–O(III) mode as a function of incident photon energy.
Published: 2006
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49. CT directed diagnostic and therapeutic pericardiocentesis: 8-year experience at a single institution

Author: Bret F. Coughlin, S. V. Klein, H. Afridi, D. Agarwal, and L. H. Schielke
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Radiography, Interventional, medicine, Humans, Radiology, Nuclear Medicine and imaging, Major complication, Single institution, Child, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Medical record, Infant, Newborn, Infant, Pericardiocentesis, Retrospective cohort study, Middle Aged, Symptomatic relief, Surgery, Cardiothoracic surgery, Child, Preschool, Emergency Medicine, Female, Radiology, Tamponade, Tomography, X-Ray Computed, business
Abstract: A retrospective review of the 8-year experience at a single institution performing more than 300 CT directed pericardiocenteses was performed. The technique, results, and complications were determined. Comparative data from the literature relating to cardiology and thoracic surgery are reviewed. A CPT code data base search was performed to identify all imaging directed pericardiocenteses at a 550 bed regional medical center between 1993 and 2001. Medical records, imaging studies, and reports as well as pertinent laboratory, chemistry and hematology values were reviewed. Demographics, results, fluid analyses, techniques, systems used and complications were recorded. Results: Three hundred and nineteen pericardiocenteses using CT localization were attempted on 261 patients. One hundred and forty-two men were included and mean age was 61 years (range 6 months to 89 years). Mean volume aspirated was 418 cc (range 0–1,875 cc). The major complication rate was 0.3%; the minor complication rate was 6.9%. Technical success was achieved in 98.4% procedures. Emergent pericardiocentesis was performed on anticoagulated patients without significant bleeding. Seventy-nine percent of patients with echocardiographic evidence of tamponade had symptomatic improvement. Patients with marked shortness of breath without other evidence of tamponade benefited symptomatically in 78%. Pericardiocenteses with CT localization is relatively safe and many patients achieve symptomatic relief.
Published: 2005
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50. TWO-DIMENSIONAL CORRELATION ANALYSIS OF SUPERCONDUCTING YNi2B2C RAMAN SPECTRA

Author: M. V. Klein, Seung Bin Kim, Young Mee Jung, and In Sang Yang
Subjects: Superconductivity, symbols.namesake, Materials science, Condensed matter physics, Phonon, Two-dimensional correlation analysis, Correlation analysis, symbols, Statistical and Nonlinear Physics, Condensed Matter Physics, Raman spectroscopy, Single crystal
Abstract: Two-dimensional (2D) correlation analysis is applied to the temperature dependence on the Raman spectra of superconducting YNi 2 B 2 C single crystal. 2D correlation analysis on the temperature dependence of the B 1g superconducting gap peak shows strong correlation with the Ni B 1g phonon peak near 200 cm -1. The analysis on the B 1g phonon peak itself shows that the peak is composed of essentially two peaks at 197 and 203 cm -1, and only the weight of the two peaks changes as the temperature changes. The result suggests that there are two distinctive environments of the Ni - B bonds in YNi 2 B 2 C system at the superconducting state.
Published: 2005
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