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Browsing by Author "Technische Universität Dresden"

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    Alcohol consumption and attributable harm in middle-income South-East Asian countries: Epidemiology and policy options
    (2020-09-01) Bundit Sornpaisarn; Kevin Shield; Jakob Manthey; Yuriko Limmade; Wah Yun Low; Vo Van Thang; Jürgen Rehm; University Medicine and Pharmacy, Hue University; University of Malaya; Technische Universität Dresden; University of Toronto; Centre for Addiction and Mental Health; Mahidol University; Sechenov First Moscow State Medical University; Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät
    © 2020 Elsevier B.V. Background Factors and policies which potentially explain the changes in alcohol consumption and related harms from 2010 to 2017 in 11 middle-income countries in the South-East Asian region (Cambodia, Lao PDR, Indonesia, the Philippines, Malaysia, Maldives, Myanmar, Sri Lanka, Thailand, Timor-Leste, and Vietnam) were examined. Methods Using secondary data from UN agencies, we analyzed trends in alcohol consumption, alcohol-attributable deaths and the burden of disease. Results Starting from a level of consumption significantly below the global average—especially among the Muslim-majority countries (Maldives, Indonesia, and Malaysia)—the majority of the countries in this region had markedly increased their alcohol consumption along with the economic development they experienced between 2010 and 2017. In fact, five middle-income countries in this region (Vietnam, Lao PDR, Cambodia, Myanmar, and Timor-Leste) were in the top 12 countries globally based on absolute increases in adult alcohol per capita consumption (APC). The Philippines and Malaysia were the exceptions, as they had reduced their APC over this period. The majority of South-East Asian countries had parallel increasing trends in the age-standardized alcohol-attributable deaths and DALYs since 2010, in contrast to global trends. While all countries put some alcohol control policies in place, there were differences in the number and strength of the policies applied, commensurate with trends in consumption. In particular, three of the countries which were most successful in reducing consumption and harm (Malaysia, Philippines, and Sri Lanka) applied more effective tax methods based on specific taxation alone or in combination with another taxation method, applying higher taxation rates and regularly increasing them over time. Conclusion To achieve the global target and the Sustainable Development Goal in reducing alcohol consumption worldwide, middle-income countries, especially lower-middle-income countries, should employ stricter alcohol control policies, and apply an appropriate excise tax on alcohol products with regular increases to reflect inflation.
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    Alcohol use and injury risk in Thailand: A case-crossover emergency department study
    (2020-07-01) Bundit Sornpaisarn; Sarnti Sornpaisarn; Kevin D. Shield; Jürgen Rehm; The Campbell Family Cancer Research Institute; McMaster University; Organisation Mondiale de la Santé; Technische Universität Dresden; University of Toronto; Centre for Addiction and Mental Health; Mahidol University; Sechenov First Moscow State Medical University
    © 2020 Australasian Professional Society on Alcohol and other Drugs Introduction and Aims: While injuries and alcohol contribute to a large proportion of the disease burden in Thailand, no well-designed underlying study has yet been published. This study aims to evaluate the relationship between acute alcohol consumption and injury risk in Thailand. Design and Methods: Using the case-crossover design, this study examined 520 injured patients aged 18 years and older from two emergency departments in Meuang District, Chiang-Mai Province, Thailand, from June to August of 2016. The case period was defined as 6 h prior to injury, the two control periods as the same 6-h period at 1 day and 7 days prior to injury. Alcohol exposure and the amount consumed were measured for these periods. Results: Twenty percent of injured patients consumed alcohol within the 6 h prior to injury, averaging 6.9 drinks during that time. The odds of injury for those individuals consuming alcoholic beverages was 5.0 (95% confidence interval 3.0, 8.2) times greater compared to non-exposure individuals; every additional drink consumed increased the odds of injury by 1.3 (95% confidence interval 1.2, 1.4). Alcohol use significantly increased the odds of sustaining an unintentional injury, intentional injury inflicted by someone else or experiencing a road traffic injury (among drivers). The dose–response analysis indicated alcohol use significantly increased the risks of unintentional injury and road traffic injuries (among drivers). Discussion and Conclusions: Exposure to alcohol increased the odds of injury in a dose-dependent fashion; hence, comprehensive, cost-effective strategies should be implemented in Thailand to reduce alcohol exposure, binge drinking and drunk driving.
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    The association between the time of alcohol drinking and injury risk in Thailand: a cross‐sectional emergency department study
    (2021-12-01) Bundit Sornpaisarn; Sarnti Sornpaisarn; Jürgen Rehm; McMaster University; Universität Hamburg; Organisation Mondiale de la Santé; Technische Universität Dresden; University of Toronto; Centre for Addiction and Mental Health; Mahidol University; Sechenov First Moscow State Medical University
    Background: Although the relationship between acute alcohol consumption and injuries is well recognized, studies exploring how the time of day the drinking commences affects alcohol-related injuries have been scarce. This contribution examines the associations between the time at which the drinking began and the duration of the drinking, the volume of alcohol consumed, the injury type, and the blood alcohol concentration (BAC) level. Method: This study employed a cross-sectional survey, which was conducted in two hospital emergency departments (ED) in Chiangmai Province, Thailand. The sample was composed of 519 injured patients aged 18 years and older. Outcome measures included the BAC and type of injury. Exposures included the quantity of alcohol consumed, the time the drinking commenced, and the pattern of drinking involved. Results: The injured patients who drank alcohol within six hours prior to sustaining their injury were more likely to get injured and present themselves at the ED at night (20:00–04:00) compared to those who sustained an injury but did not drink in the hours prior. However, this relationship was only true for unintentional injuries, not intentional ones. The majority of participants consumed their first drink between 16:00 and 20:00. On average, among the 104 patients who drank prior to sustaining an injury, the total amount of alcohol consumed was 6.9 drinks, the duration of drinking was 2.6 h, the rate of drinking was 6.0 drinks/hour, and the BAC was 0.119 gm%. Every drink increased the BAC by 0.012 gm% and each year of increasing age increased the BAC by 0.003 gm%. People who were older, less educated, and drank more frequently tended to have their first drink earlier than other drinkers. An earlier start to their drinking resulted in a faster pace of drinking and a higher BAC. Conclusions: BAC increased with the total amount of alcohol consumed and the age of the drinker. Different groups of people had their first drink at different times of the day, resulting in differences in the rate of drinking, the BAC, the time of injury, and the time they presented to the ED after injury.
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    The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients – a posthoc propensity score–weighted cohort analysis of the LAS VEGAS study
    (2021-12-01) Guido Mazzinari; Ary Serpa Neto; Sabrine N.T. Hemmes; Goran Hedenstierna; Samir Jaber; Michael Hiesmayr; Markus W. Hollmann; Gary H. Mills; Marcos F. Vidal Melo; Rupert M. Pearse; Christian Putensen; Werner Schmid; Paolo Severgnini; Hermann Wrigge; Oscar Diaz Cambronero; Lorenzo Ball; Marcelo Gama de Abreu; Paolo Pelosi; Marcus J. Schultz; Wolfgang Kroell; Helfried Metzler; Gerd Struber; Thomas Wegscheider; Hans Gombotz; Bernhard Urbanek; David Kahn; Mona Momeni; Audrey Pospiech; Fernande Lois; Patrice Forget; Irina Grosu; Jan Poelaert; Veerle van Mossevelde; Marie Claire van Malderen; Dimitri Dylst; Jeroen van Melkebeek; Maud Beran; Stefan de Hert; Luc De Baerdemaeker; Bjorn Heyse; Jurgen Van Limmen; Piet Wyffels; Tom Jacobs; Nathalie Roels; Ann De Bruyne; Stijn van de Velde; Brigitte Leva; Sandrine Damster; Benoit Plichon; Marina Juros-Zovko; Dejana Djonovic-Omanovic; Selma Pernar; Josip Zunic; Petar Miskovic; Antonio Zilic; Slavica Kvolik; Dubravka Ivic; Darija Azenic-Venzera; Sonja Skiljic; Hrvoje Vinkovic; Ivana Oputric; Kazimir Juricic; Vedran Frkovic; Jasminka Kopic; Ivan Mirkovic; Nenad Karanovic; Mladen Carev; Natasa Dropulic; Jadranka Pavicic Saric; Gorjana Erceg; Matea Bogdanovic Dvorscak; Branka Mazul-Sunko; Anna Marija Pavicic; Tanja Goranovic; Branka Maldini; Tomislav Radocaj; Zeljka Gavranovic; Inga Mladic-Batinica; Mirna Sehovic; Petr Stourac; Hana Harazim; Olga Smekalova; Martina Kosinova; Tomas Kolacek; Kamil Hudacek; Michal Drab; Jan Brujevic; Katerina Vitkova; Katerina Jirmanova; Ivana Volfova; Paula Dzurnakova; Katarina Liskova; Radovan Dudas; Radek Filipsky; Samir el Kafrawy; Hisham Hosny Abdelwahab; Tarek Metwally; Ahmed Abdel-Razek; Ahmed Mostafa El-Shaarawy; Wael Fathy Hasan; Université de Montpellier; IRCCS San Martino Polyclinic Hospital; Hospital Universitari i Politècnic La Fe; Universitätsklinikum Bonn; Massachusetts General Hospital; Università degli Studi di Genova; Queen Mary University of London; Technische Universität Dresden; Hospital Israelita Albert Einstein; Mahidol University; Medizinische Universität Wien; Nuffield Department of Medicine; Universidade de São Paulo; BG-Kliniken Bergmannstrost Halle; Università degli Studi dell'Insubria; Uppsala Universitet; The University of Sheffield; Amsterdam UMC - University of Amsterdam
    Background: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time–weighted average ΔP (ΔPTW) with PPCs. We also tested the association of ΔPTW with intraoperative adverse events. Methods: Posthoc retrospective propensity score–weighted cohort analysis of patients undergoing open or closed abdominal surgery in the ‘Local ASsessment of Ventilatory management during General Anaesthesia for Surgery’ (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events. Results: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔPTW was not different between groups. The association of ΔPTW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P < 0.001 versus 1.05 [95%CI 1.05 to 1.05], P < 0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P < 0.001). The association of ΔPTW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12– to 1.14], P < 0.001 versus 1.07 [95%CI 1.05 to 1.10], P < 0.001; risk difference 0.05 [95%CI 0.030.07], P < 0.001). Conclusions: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery. Trial registration: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223).
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    Dissecting the low catalytic capability of flavin-dependent halogenases
    (2021-01-01) Aisaraphon Phintha; Kridsadakorn Prakinee; Aritsara Jaruwat; Narin Lawan; Surawit Visitsatthawong; Chadaporn Kantiwiriyawanitch; Warangkhana Songsungthong; Duangthip Trisrivirat; Pirom Chenprakhon; Adrian Mulholland; Karl Heinz van Pée; Penchit Chitnumsub; Pimchai Chaiyen; Vidyasirimedhi Institute of Science and Technology; University of Bristol; Technische Universität Dresden; Mahidol University; Thailand National Center for Genetic Engineering and Biotechnology; Chiang Mai University
    Although flavin-dependent halogenases (FDHs) are attractive biocatalysts, their practical applications are limited because of their low catalytic efficiency. Here, we investigated the reaction mechanisms and structures of tryptophan 6-halogenase (Thal) from Streptomyces albogriseolus using stopped-flow, rapid-quench flow, quantum/mechanics molecular mechanics calculations, crystallography, and detection of intermediate (hypohalous acid [HOX]) liberation. We found that the key flavin intermediate, C4a-hydroperoxyflavin (C4aOOH-FAD), formed by Thal and other FDHs (tryptophan 7-halogenase [PrnA] and tryptophan 5-halogenase [PyrH]), can react with I−, Br−, and Cl− but not F− to form C4a-hydroxyflavin and HOX. Our experiments revealed that I− reacts with C4aOOH-FAD the fastest with the lowest energy barrier and have shown for the first time that a significant amount of the HOX formed leaks out as free HOX. This leakage is probably a major cause of low product coupling ratios in all FDHs. Site-saturation mutagenesis of Lys79 showed that changing Lys79 to any other amino acid resulted in an inactive enzyme. However, the levels of liberated HOX of these variants are all similar, implying that Lys79 probably does not form a chloramine or bromamine intermediate as previously proposed. Computational calculations revealed that Lys79 has an abnormally lower pKa compared with other Lys residues, implying that the catalytic Lys may act as a proton donor in catalysis. Analysis of new X-ray structures of Thal also explains why premixing of FDHs with reduced flavin adenine dinucleotide generally results in abolishment of C4aOOH-FAD formation. These findings reveal the hidden factors restricting FDHs capability which should be useful for future development of FDHs applications.
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    An efficient highly flexible strain sensor: Enhanced electrical conductivity, piezoresistivity and flexibility of a strongly piezoresistive composite based on conductive carbon black and an ionic liquid
    (2018-10-01) Jirawat Narongthong; Amit Das; Hai Hong Le; Sven Wießner; Chakrit Sirisinha; Technische Universität Dresden; Mahidol University; Tampere University of Technology; Leibniz-Institut für Polymerforschung Dresden e.V.
    © 2018 Elsevier Ltd Flexible strain sensors based on conductive carbon black (CB) filled styrene-butadiene rubber were developed. The use of ionic liquid (IL) allows improvement of the filler dispersion, rubber-filler interaction and flexibility of the sample that finally enhances the piezoresistive performance and the sensibility. At filler loading close to the percolation threshold, the electrical conductivity increases by two orders of magnitude when the IL/CB ratio is increased from 0 to 1.5. In contrast to the use of normal plasticisers, the loss in piezoresistivity at low strains is overcome. The sensitivity at 2.5% strain using an IL/CB ratio of 1.5 is about 600% higher compared with the sample without IL. Also, the response consistency becomes better with higher IL/CB ratios. Moreover, the use of IL allows the composites to be deformed more easily while still providing high responsivity to small strains. This enables the construction of better flexible strain sensors with long-term stability.
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    Fewer Cancer Cases in 4 Countries of the WHO European Region in 2018 through Increased Alcohol Excise Taxation: A Modelling Study
    (2021-05-01) Pol Rovira; Carolin Kilian; Maria Neufeld; Harriet Rumgay; Isabelle Soerjomataram; Carina Ferreira-Borges; Kevin D. Shield; Bundit Sornpaisarn; Jürgen Rehm; Agencia de Salut Publica de Barcelona; International Agency for Research on Cancer; Technische Universität Dresden; University of Toronto; Centre for Addiction and Mental Health; Mahidol University; Sechenov First Moscow State Medical University; WHO European Office for Prevention and Control of Noncommunicable Diseases
    Introduction: Prevention of cancer has been identified as a major public health priority for Europe, and alcohol is a leading risk factor for various types of cancer. This contribution estimates the number of cancer cases that could have potentially been averted in 2018 in 4 European countries if an increase in alcohol excise taxation had been applied. Methods: Current country and beverage-specific excise taxation of 4 member states of the WHO European Region (Germany, Italy, Kazakhstan, and Sweden) was used as a baseline, and the potential impacts of increases of 20, 50, and 100% to current excise duties were modelled. A sensitivity analysis was performed, replacing the current tax rates in the 4 countries by those levied in Finland. The resulting increase in tax was assumed to be fully incorporated into the consumer price, and beverage-specific price elasticities of demand were obtained from meta-analyses, assuming less elasticity for heavy drinkers. Model estimates were applied to cancer incidence rates for the year 2018. Results: In the 4 countries, >35,000 cancer cases in 2018 were caused by alcohol consumption, with the highest rate of alcohol-attributable cancers recorded in Germany and the lowest in Sweden. An increase in excise duties on alcohol would have significantly reduced these numbers, with between 3 and 7% of all alcohol-attributable cancer cases being averted if taxation had been increased by 100%. If the 4 countries were to adopt an excise taxation level equivalent to the one currently imposed in Finland, an even higher proportion of alcohol-attributable cancers could be avoided, with Germany alone experiencing 1,600 fewer cancer cases in 1 year. Discussion/Conclusion: Increasing excise duties can markedly reduce cancer incidence in European countries.
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    The fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature
    (2018-05-01) G. Mazzinari; L. Ball; A. Serpa Neto; C. L. Errando; A. M. Dondorp; L. D. Bos; M. Gama de Abreu; P. Pelosi; M. J. Schultz; Ospedale Policlinico San Martino; Hospital Universitari i Politècnic La Fe; Technische Universität Dresden; Hospital Israelita Albert Einstein; Hospital General Universitario de Valencia; Mahidol University; Amsterdam UMC - University of Amsterdam
    © 2018 British Journal of Anaesthesia The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow-up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter-quartile range) sample size was 150 (70–300) patients. The FI was 4 (2–17) and 3 (2–7), and the number of patients lost to follow-up was 0 (0–18) and 0 (0–6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow-up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P-values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow-up could possibly have changed the reported effect.
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    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
    (2021-01-01) Daniel J. Klionsky; Amal Kamal Abdel-Aziz; Sara Abdelfatah; Mahmoud Abdellatif; Asghar Abdoli; Steffen Abel; Hagai Abeliovich; Marie H. Abildgaard; Yakubu Princely Abudu; Abraham Acevedo-Arozena; Iannis E. Adamopoulos; Khosrow Adeli; Timon E. Adolph; Annagrazia Adornetto; Elma Aflaki; Galila Agam; Anupam Agarwal; Bharat B. Aggarwal; Maria Agnello; Patrizia Agostinis; Javed N. Agrewala; Alexander Agrotis; Patricia V. Aguilar; S. Tariq Ahmad; Zubair M. Ahmed; Ulises Ahumada-Castro; Sonja Aits; Shu Aizawa; Yunus Akkoc; Tonia Akoumianaki; Hafize Aysin Akpinar; Ahmed M. Al-Abd; Lina Al-Akra; Abeer Al-Gharaibeh; Moulay A. Alaoui-Jamali; Simon Alberti; Elísabet Alcocer-Gómez; Cristiano Alessandri; Muhammad Ali; M. Abdul Alim Al-Bari; Saeb Aliwaini; Javad Alizadeh; Eugènia Almacellas; Alexandru Almasan; Alicia Alonso; Guillermo D. Alonso; Nihal Altan-Bonnet; Dario C. Altieri; Élida M.C. Álvarez; Sara Alves; Cristine Alves da Costa; Mazen M. Alzaharna; Marialaura Amadio; Consuelo Amantini; Cristina Amaral; Susanna Ambrosio; Amal O. Amer; Veena Ammanathan; Zhenyi An; Stig U. Andersen; Shaida A. Andrabi; Magaiver Andrade-Silva; Allen M. Andres; Sabrina Angelini; David Ann; Uche C. Anozie; Mohammad Y. Ansari; Pedro Antas; Adam Antebi; Zuriñe Antón; Tahira Anwar; Lionel Apetoh; Nadezda Apostolova; Toshiyuki Araki; Yasuhiro Araki; Kohei Arasaki; Wagner L. Araújo; Jun Araya; Catherine Arden; Maria Angeles Arévalo; Sandro Arguelles; Esperanza Arias; Jyothi Arikkath; Hirokazu Arimoto; Aileen R. Ariosa; Darius Armstrong-James; Laetitia Arnauné-Pelloquin; Angeles Aroca; Daniela S. Arroyo; Ivica Arsov; Rubén Artero; Dalia Maria Lucia Asaro; Michael Aschner; Milad Ashrafizadeh; Osnat Ashur-Fabian; Atanas G. Atanasov; Alicia K. Au; Patrick Auberger; Holger W. Auner; Laure Aurelian; Departement Cellulaire en Moleculaire Geneeskunde; Université Côte d'Azur; The Francis Crick Institute; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Indian Institute of Technology Ropar; Centre du Cancer Segal; Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences; Universidade Nove de Julho; TIGEM Telethon Institute of Genetics and Medicine; Biotech Research & Innovation Centre; Islamic University of Gaza; Gulf Medical University; Universidad de Sevilla; NOVA Medical School - Faculdade de Ciências Médicas, Universidade Nova de Lisboa; Tokyo University of Pharmacy and Life Sciences; Stanford University School of Medicine; Sapienza Università di Roma; The Jikei University School of Medicine; Johannes Gutenberg-Universität Mainz; Istituto Europeo di Oncologia; Aarhus Universitet; Alma Mater Studiorum Università di Bologna; Universidad del Pais Vasco; Universite Paul Sabatier Toulouse III; Ben-Gurion University of the Negev; The University of Alabama at Birmingham; Università degli Studi di Camerino; Universität Wien; University of Michigan, Ann Arbor; The University of Sydney; Osaka University; University of Cologne; University of California, San Francisco; UC Davis School of Medicine; National Institute of Neuroscience, Kodaira; CSIC - Instituto Cajal (IC); Leibniz Institut fur Pflanzenbiochemie; UiT The Arctic University of Norway; Cleveland Clinic Foundation; University of Bristol; Imperial College Faculty of Medicine; Università della Calabria; Rajshahi University; Institutionen för Experimentell Medicinsk Vetenskap; Technische Universität Dresden; Kræftens Bekæmpelse; Università degli Studi di Palermo; University of Toronto; Ain Shams University; Cedars-Sinai Medical Center; Wilmer Eye Institute; Medical Research Council; The University of Tennessee, Knoxville; Università degli Studi di Pavia; Universidade Federal de São Paulo; UT Medical Branch at Galveston; Universidade Federal de Vicosa; University of Maryland School of Medicine; University of Crete Medical School; Hospital Universitari de Bellvitge; Medizinische Universität Wien; Max Rady College of Medicine, University of Manitoba; The Wistar Institute; The Institute of Cancer Research; Sabancı Üniversitesi; University of Dundee; Tohoku University; Medizinische Universitat Innsbruck; Howard University College of Medicine; Hebrew University of Jerusalem; National Eye Institute (NEI); City of Hope National Med Center; Universidade do Porto; City University of New York; Safar Center for Resuscitation Research; Koç Üniversitesi; Medizinische Universität Graz; Newcastle University; Universidad Mayor; Colby College; Tel Aviv University; Pasteur Institute of Iran; National Heart, Lung, and Blood Institute (NHLBI); Iowa State University; The Ohio State University; Universidad de la Laguna; Helsingin Yliopisto; Universitat de València; Nihon University; Albert Einstein College of Medicine of Yeshiva University; Universitat de Barcelona; Universidad de Buenos Aires; Northeastern Ohio Universities Colleges of Medicine and Pharmacy; Inserm; Universidad Nacional de Córdoba; Save as Ravi Manjithaya; Interdisciplinary Research Structure for Biotechnology and Biomedicine (ERI BIOTECMED); Inflammation Research Center
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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    Intraabdominal pressure targeted positive end-expiratory pressure during laparoscopic surgery: An open-label, nonrandomized, crossover, clinical trial
    (2020-01-01) Guido Mazzinari; Oscar Diaz-Cambronero; Jose Miguel Alonso-Iñigo; Nuria Garcia-Gregorio; Begoña Ayas-Montero; Jose Luis Ibañez; Ary Serpa Neto; Lorenzo Ball; Marcelo Gama De Abreu; Paolo Pelosi; Javier Maupoey; Maria Pilar Argente Navarro; Marcus J. Schultz; Ospedale Policlinico San Martino; Hospital Universitari i Politècnic La Fe; Università degli Studi di Genova; Instituto do Coracao do Hospital das Clinicas; Technische Universität Dresden; Hospital Israelita Albert Einstein; Mahidol University; Nuffield Department of Clinical Medicine; Amsterdam UMC - University of Amsterdam
    Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved. Background: Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumo-peritoneum-related rises in driving pressure. Methods: Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. results: Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. conclusions: Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.
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    Ionic liquid enabled electrical-strain tuning capability of carbon black based conductive polymer composites for small-strain sensors and stretchable conductors
    (2019-04-12) Jirawat Narongthong; Hai Hong Le; Amit Das; Chakrit Sirisinha; Sven Wießner; Technische Universität Dresden; Mahidol University; Tampere University of Technology; Leibniz-Institut für Polymerforschung Dresden e.V.
    © 2019 Elsevier Ltd Conductive carbon black (CB) filled styrene-butadiene rubber composites with tuneable electrical-strain behaviour were prepared based on the use of ionic liquid (IL). The addition of IL is also capable of improving electrical conductivity and flexibility, thus, enabling use in applications such as small-strain sensors and stretchable conductors. For small-strain sensors, at small strains up to 9%, the composite with IL/CB ratio of 1.5 gives sensitivity up to about 700% higher than that without IL. Also, the sensing consistency is enhanced with increased IL/CB ratios. For stretchable conductors, the use of IL makes the alignment of the aggregate more effective, thus allowing an extension of the maximum conducting strain. This can be extended from less than 40% to approximately 180% using an IL/CB ratio of 1.5 in combination with an adjusted mixing time.
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    Modeling intra-abdominal volume and respiratory driving pressure during pneumoperitoneum insufflation — A patient-level data meta-analysis
    (2021-03-01) Guido Mazzinari; Oscar Diaz-Cambronero; Ary Serpa Neto; Antonio Cañada Martínez; Lucas Rovira; María Pilar Argente Navarro; Manu L.N.G. Malbrain; Paolo Pelosi; Marcelo Gama De Abreu; Markus W. Hollmann; Marcus J. Schultz; Faculteit Geneeskunde en Farmacie; IRCCS San Martino Polyclinic Hospital; Instituto de Investigación Sanitaria La Fe; Universitair Ziekenhuis Brussel; Hospital Universitari i Politècnic La Fe; Università degli Studi di Genova; Technische Universität Dresden; Hospital Israelita Albert Einstein; Hospital General Universitario de Valencia; Mahidol University; Nuffield Department of Medicine; Universidade de São Paulo; Amsterdam UMC - University of Amsterdam; International Fluid Academy; Spanish Clinical Research Network (SCReN); Outcomes Research Consortium
    During pneumoperitoneum, intra-abdominal pressure (IAP) is usually kept at 12–14 mmHg. There is no clinical benefit in IAP increments if they do not increase intra-abdominal volume IAV. We aimed to estimate IAV (DIAV) and respiratory driving pressure changes (DPRS) in relation to changes in IAP (DIAP). We carried out a patient-level meta-analysis of 204 adult patients with available data on IAV and DPRS during pneumoperitoneum from three trials assessing the effect of IAP on postoperative recovery and airway pressure during laparoscopic surgery under general anesthesia. The primary endpoint was DIAV, and the secondary endpoint was DPRS. The endpoints’ response to DIAP was modeled using mixed multivariable Bayesian regression to estimate which mathematical function best fitted it. IAP values on the pressure–volume (PV) curve where the endpoint rate of change according to IAP decreased were identified. Abdomino-thoracic transmission (ATT) rate, that is, the rate DPRS change to DIAP was also estimated. The best-fitting function was sigmoid logistic and linear for IAV and DPRS response, respectively. Increments in IAV reached a plateau at 6.0 [95%CI 5.9–6.2] L. DIAV for each DIAP decreased at IAP ranging from 9.8 [95%CI 9.7–9.9] to 12.2 [12.0–12.3] mmHg. ATT rate was 0.65 [95%CI 0.62–0.68]. One mmHg of IAP raised DPRS 0.88 cmH2O. During pneumoperitoneum, IAP has a nonlinear relationship with IAV and a linear one with DPRS. IAP should be set below the point where IAV gains diminish. NEW & NOTEWORTHY We found that intra-abdominal volume changes related to intra-abdominal pressure increase reached a plateau with diminishing gains in commonly used pneumoperitoneum pressure ranges. We also found a linear relationship between intra-abdominal pressure and respiratory driving pressure, a known marker of postoperative pulmonary complications.
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    P−P Condensation and P−N/P−P Bond Metathesis: Facile Synthesis of Cationic Tri- and Tetraphosphanes
    (2020-02-24) Clemens Taube; Kai Schwedtmann; Medena Noikham; Ekasith Somsook; Felix Hennersdorf; Robert Wolf; Jan J. Weigand; Universität Regensburg; Technische Universität Dresden; Mahidol University
    © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. [LCRP((PhP)2C2H4)][OTf] (4 a,b[OTf]) and [LCiPrP(PPh2)2][OTf] (5 b[OTf]) were prepared from the reaction of imidazoliumyl-substituted dipyrazolylphosphane triflate salts [LCRP(pyr)2][OTf] (3 a,b[OTf]; a: R=Me, b=iPr; LCR=1,3-dialkyl-4,5-dimethylimidazol-2-yl; pyr=3,5-dimethylpyrazol-1-yl) with the secondary phosphanes PhP(H)C2H4P(H)Ph) and Ph2PH. A stepwise double P−N/P−P bond metathesis to catena-tetraphosphane-2,3-diium triflate salt [(Ph2P)2(LCMeP)2][OTf]2 (7 a[OTf]2) is observed when reacting 3 a[OTf] with diphosphane P2Ph4. The coordination ability of 5 b[OTf] was probed with selected coinage metal salts [Cu(CH3CN)4]OTf, AgOTf and AuCl(tht) (tht=tetrahydrothiophene). For AuCl(tht), the helical complex [{(Ph2PPLCiPr)Au}4][OTf]4 (9[OTf]4) was unexpectedly formed as a result of a chloride-induced P−P bond cleavage. The weakly coordinating triflate anion enables the formation of the expected copper(I) and silver(I) complexes [(5 b)M(CH3CN)3][OTf]2 (M=Cu, Ag) (10[OTf]2, 11[OTf]2).
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    Pentabromopseudilin: a myosin V inhibitor suppresses TGF-β activity by recruiting the type II TGF-β receptor to lysosomal degradation
    (2018-01-01) Wang Shih-Wei; Chung Chih-Ling; Yu Chen Kao; René Martin; Hans Joachim Knölker; Meng Shin Shiao; Chun Lin Chen; Technische Universität Dresden; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; National Sun Yat-Sen University Taiwan
    © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial–mesenchymal transition in epithelial cells. PBrP inhibits TGF-β signalling by reducing the cell-surface expression of type II TGF-β receptor (TβRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TβRII turnover and the subsequent reduction of TGF-β signalling. Because, TGF-β signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.
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    Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT
    (2018-12-01) Fabienne D. Simonis; Carmen S.V. Barbas; Antonio Artigas-Raventós; Jaume Canet; Rogier M. Determann; James Anstey; Goran Hedenstierna; Sabrine N.T. Hemmes; Greet Hermans; Michael Hiesmayr; Markus W. Hollmann; Samir Jaber; Ignacio Martin-Loeches; Gary H. Mills; Rupert M. Pearse; Christian Putensen; Werner Schmid; Paolo Severgnini; Roger Smith; Tanja A. Treschan; Edda M. Tschernko; Marcos F. Vidal Melo; Hermann Wrigge; Marcelo Gama de Abreu; Paolo Pelosi; Marcus J. Schultz; Ary Serpa Neto; Barry Dixon; Uniklinik Düsseldorf; KU Leuven– University Hospital Leuven; Universitäts-Klinikum Bonn und Medizinische Fakultät; Massachusetts General Hospital; Hospital Universitari Germans Trias i Pujol; Hopital Saint-Eloi; Dresden University Faculty of Medicine and University Hospital Carl Gustav Carus; Università degli Studi di Genova; KU Leuven; Barts and The London School of Medicine and Dentistry; Technische Universität Dresden; Hospital Israelita Albert Einstein; Mahidol University; Medizinische Universitat Wien; Trinity College Dublin; Hospital de Sabadell; Universidade de Sao Paulo - USP; Universität Leipzig; Università degli Studi dell'Insubria; Uppsala Universitet; St. Vincent's Hospital Melbourne; Amsterdam UMC - University of Amsterdam; Irish Centre for Vascular Biology; Sheffield Teaching Hospital
    © 2018, The Author(s). Background: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients. Methods: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality. Results: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the ‘Lung Injury Prediction Score’ and received lower maximum airway pressure (Pmax), driving pressure (ΔP), positive end-expiratory pressure, and FiO2 levels. Tidal volume size was similar between the groups. Higher Pmax was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence. Conclusions: Higher Pmax was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS. Trial Registration ClinicalTrials.gov (NCT01868321).
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    Pre-clinical validation of a turbine-based ventilator for invasive ventilation–The ACUTE-19 ventilator
    (2021-01-01) J. M. Alonso-Iñigo; G. Mazzinari; M. Casañ-Pallardó; J. I. Redondo-García; J. Viscasillas-Monteagudo; A. Gutierrez-Bautista; J. Ramirez-Faz; P. Alonso-Pérez; S. Díaz-Lobato; A. S. Neto; O. Diaz-Cambronero; P. Argente-Navarro; M. Gama de Abreu; P. Pelosi; M. J. Schultz; IRCCS San Martino Polyclinic Hospital; Hospital Universitari i Politècnic La Fe; Università degli Studi di Genova; Cleveland Clinic Foundation; Technische Universität Dresden; Hospital Israelita Albert Einstein; Mahidol University; Hospital General de Castellon; Nuffield Department of Medicine; Universidade de São Paulo; Universidad Cardenal Herrera-CEU; Universidad de Córdoba; Amsterdam UMC - University of Amsterdam; Nippon Gases HealthCare & Oximesa NG
    Background: The severe acute respiratory syndrome-coronavirus 2 pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. Methods: Validation consisted of (a) testing tidal volume delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (−0.3 cmH2O [95% CI −0.9 to 0.3]; P = .409), and positive end-expiratory pressure was marginally different (0.3 cmH2O [95% CI 0.2 to 0.3]; P < .001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias −0.29 [limits of agreement 0.82 to −1.42], and mean bias 0.56 [limits of agreement 1.94 to −0.81], at a plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome induction. Conclusions: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The ACUTE-19 can provide the basis for the development of a future affordable commercial ventilator.
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    Risk stratification in pulmonary arterial hypertension using Bayesian analysis
    (2020-08-01) Manreet K. Kanwar; Mardi Gomberg-Maitland; Marius Hoeper; Christine Pausch; David Pittow; Geoff Strange; James J. Anderson; Carol Zhao; Jacqueline V. Scott; Marek J. Druzdzel; Jidapa Kraisangka; Lisa Lohmueller; James Antaki; Raymond L. Benza; Cornell University College of Engineering; University of Notre Dame Australia; West Penn Allegheny Health System; Carnegie Mellon University; School of Medicine and Health Sciences; Medizinische Hochschule Hannover (MHH); Technische Universität Dresden; The Ohio State University Wexner Medical Center; Mahidol University; Bialystok University of Technology; Sunshine Coast University Hospital; A Janssen Pharmaceutical Company of Johnson & Johnson
    © ERS 2020 Background: Current risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network (BN) based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0. Methods: We derived a Tree Augmented Naïve Bayes model (titled PHORA) to predict one-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in COMPERA and PHSANZ registry). Patients were classified as low, intermediate and high-risk (<5%, 5-20% and > 10% 12-month mortality, respectively) based on the 2015 ESC/ERS guidelines. Results: PHORA had an AUC of 0.80 for predicting one-year survival, which was an improvement over REVEAL 2.0 (AUC of 0.76). When validated in COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80 respectively. One-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (P<.001), with excellent separation between low-, intermediate-, and high-risk groups in all three registries. Conclusion: Our BN derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of BN based model’s ability to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.
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    A STING antagonist modulating the interaction with STIM1 blocks ER-to-Golgi trafficking and inhibits lupus pathology
    (2021-04-01) Thaneas Prabakaran; Anne Troldborg; Sarinya Kumpunya; Isara Alee; Emilija Marinković; Samuel J. Windross; Ramya Nandakumar; Ryo Narita; Bao cun Zhang; Mikkel Carstensen; Pichpisith Vejvisithsakul; Mikkel H.S. Marqvorsen; Marie B. Iversen; Christian K. Holm; Lars J. Østergaard; Finn Skou Pedersen; Trairak Pisitkun; Rayk Behrendt; Prapaporn Pisitkun; Søren R. Paludan; Ramathibodi Hospital; Aarhus Universitet; Chulalongkorn University; Aarhus Universitetshospital; Technische Universität Dresden
    Background: Nucleic acids are potent stimulators of type I interferon (IFN-I) and antiviral defense, but may also promote pathological inflammation. A range of diseases are characterized by elevated IFN-I, including systemic lupus erythematosus (lupus). The DNA-activated cGAS-STING pathway is a major IFN-I-inducing pathway, and activation of signaling is dependent on trafficking of STING from the ER to the Golgi. Methods: Here we used cell culture systems, a mouse lupus model, and material from lupus patients, to explore the mode of action of a STING antagonistic peptide, and its ability to modulate disease processes. Findings: We report that the peptide ISD017 selectively inhibits all known down-stream activities of STING, including IFN-I, inflammatory cytokines, autophagy, and apoptosis. ISD017 blocks the essential trafficking of STING from the ER to Golgi through a mechanism dependent on the STING ER retention factor STIM1. Importantly, ISD017 blocks STING activity in vivo and ameliorates disease development in a mouse model for lupus. Finally, ISD017 treatment blocks pathological cytokine responses in cells from lupus patients with elevated IFN-I levels. Interpretation: These data hold promise for beneficial use of STING-targeting therapy in lupus. Funding: The Novo Nordisk Foundation, The European Research Council, The Lundbeck Foundation, European Union under the Horizon 2020 Research, Deutsche Forschungsgemeinschaft, Chulalongkorn University.
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    Strain-rate independent small-strain-sensor: Enhanced responsiveness of carbon black filled conductive rubber composites at slow deformation by using an ionic liquid
    (2020-03-01) Jirawat Narongthong; Sven Wießner; Sakrit Hait; Chakrit Sirisinha; Klaus Werner Stöckelhuber; Technische Universität Dresden; Mahidol University; Leibniz-Institut für Polymerforschung Dresden e.V.
    © 2019 Elsevier Ltd Small-strain-sensors, based on conductive carbon black (CB) filled conductive rubber composites (CRCs), have been developed. An ionic liquid (IL) was used to improve the way that the piezoresistive response is independent of strain rate at small strains. Cyclic sensing behaviour at small strains was investigated under a sequential alteration of strain rates. At small strains, the CRCs without IL respond inefficiently to slow deformation cycles, giving a strain-rate dependent sensitivity. On the contrary, the presence of IL enhances the response to slow deformations. At elongations up to 3%, the loosely packed conducting parts and the sufficient rubber-filler interaction achieved with the use of an IL/CB ratio of 1.0 make the piezoresistive responses efficiently independent of the strain rates. Also, the sensitivity is at least threefold higher, compared with CRCs without IL. So, the IL enables the construction of strain-rate independent small-strain-sensor.
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    Strategies used to initiate the first alcohol control law in Thailand: Lessons learned for other low- and middle-income countries
    (2020-12-01) Bundit Sornpaisarn; Jürgen Rehm; Technische Universität Dresden; University of Toronto; Centre for Addiction and Mental Health; Mahidol University; Sechenov First Moscow State Medical University
    © 2020 Elsevier B.V. Thailand enacted its first-ever alcohol control law in February of 2008. The process, from its inception to enactment, took a total of two years and eight months. Using an historical analysis approach, the authors describe the policy advocates’ activities aimed at gaining acceptance for the alcohol control policy, and provide advice for policy advocates attempting to pass similar laws in other countries. The advocacy process went through three distinct stages: an agenda-setting stage, followed by a policy-formulation stage and a legitimization stage. The agenda-setting stage involved educating the public about the harmful use of alcohol and its effect on society; during the second stage, an appropriate policy response was drafted and, lastly, during the legitimization phase, policy advocates navigated the political landscape in order to win final approval for the proposed policy. A tri-party coalition strategy (known as the ‘triangle that moves the mountain’ strategy) was employed which synchronized the work of three forces, each representing one of the three points of a triangle—of policy, knowledge, and civic expertise—coupled with media advocacy activities in order to increase the public and government acceptance of the proposed law. The public's view of the proposed law was critical to influence politicians to favour its adoption. While the knowledge and civic forces play a larger role during the agenda-setting and policy-formulation stages, the policy force was more active during the legitimization stage. Lastly, having a funding agency in place, such as Thai Health in this example, to provide a sustained source of funds for health promotion initiatives was critically important for policy advocates. Economic growth is an important determinant of increased consumption of alcohol per capita, and Thailand's experience of passing its first alcohol control law may serve as a useful guide for other low- or middle-income countries wishing to put a national alcohol control law in place.

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