In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings. ; Funding Agencies|Swedish Heart and Lung Foundation; Marianne and Marcus Wallenberg Foundation; Wellcome Trust [201344/Z/16/Z]; NIHR Oxford Biomedical Research Centre; NIHR Oxford Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance [HPRU-2012-10041]; Health Innovation Challenge Fund [T5-358, HICF-T5-342, WT098600]; German Center for Infection Research (DZIF); European Union TB-PAN-NET [FP7-223681]; PathoNgenTrace [278864]; UK Department of Health; Pacific Biosciences, Inc.; Illumina, Inc.; Colciencias; Hain Lifescience
Invasive alien species (IAS) are a significant and growing problem worldwide. In Europe, some aspects of IAS have been addressed through existing legal instruments, but these are far from sufficient to tackle the problem comprehensively. The FINS II Conference considered the relevance of Top 20 IAS issues (Top 10 threats and opportunities) for Europe determined at the 1st Freshwater Invasiveness – Networking for Strategy (FINS I) conference held in Ireland in 2013. Using a similar format of sequential group voting, threats from FINS I (lack of funding, of awareness and education, poor communication) and several new threats (lack of lead agencies, of standardized management and of common approach, insufficient monitoring and management on private property) were identified by 80 academics, applied scientists, policy makers and stakeholders from 14 EU and three non-EU countries (including 10 invited speakers) during four workshop break-out sessions (legislation remit in both EU/non-EU countries, best management and biosecurity practice for control, data management and early warning, pathways of introductions and citizen science). Identified opportunities include improved cooperation and communication, education and leadership to enhance public awareness and stakeholder participation, systems establishment for early detection, rapid response, monitoring and management of IAS using standardised methods of data collection, storage and usage. The sets of threats and opportunities identified underline the importance of international cooperation on IAS issues in communication, education and funding as priorities, as well as in standardization of legislation, control methods and best practise of research.
In October, 1985, discussions were held in Santiago in regard to the possibility of organizing a minerals industry conference in Chile in November, 1986, under the auspices of the Institution of Mining and Metallurgy and in association with other bodies and organizations. I, in turn, was asked to chair the Organizing Committee and at our first meeting in London in November, 1985, we realized how little time we had if we were to meet the date proposed. In the event, thanks to considerable support from the Organizing Committee and others, coupled with the very good response from authors, we were able to put together a programme on a variety of topics, with some particular emphasis on operations in South America, and with special reference to Chile, that we regard as attractive. This is the first conference to have been organized by the Institution of Mining and Metallurgy in Chile, but it is intended that it should initiate a series to be held in Latin American countries. Chile has a long and healthy mining tradition and it is fitting, therefore, that it should have been chosen for the first such conference.
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13 Pages, 1 Figure, 4 tables. The authors' affiliations are listed in the Supplementary Appendix, available at NEJM.org. Supplementary Material, available at http://dx.doi.org/10.1056/NEJMoa1800474 ; BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.). ; Supported by grants from the Bill and Melinda Gates Foundation (OPP1133541, to CRyPTIC, plus separate support to Dr. Rodwell), a Wellcome Trust/Newton Fund–MRC Collaborative Award (200205/Z/15/Z, to CRyPTIC), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, the NIHR Biomedical Research Centre at Barts, the NIHR Biomedical Research Centre at Imperial, the NIHR and NHS England (to the 100,000 Genomes Project, which is managed by Genomics England, a wholly owned company of the U.K. Department of Health), the Wellcome Trust, the Medical Research Council, Public Health England, a grant from the National Science and Technology Key Program of China (2014ZX10003002), a grant from the National Basic Research program of China (2014CB744403), a grant from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000), a grant from the European Commission Seventh Framework Program (FP7/2007-2013, to Borstel under grant agreement 278864 in the framework of the Patho-NGen-Trace project), the German Center for Infection Research (to Borstel), Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG), the Belgian Ministry of Social Affairs (to the Belgian Reference Center for Tuberculosis and Mycobacteria from Bacterial Diseases Service through a fund within the Health Insurance System), the French governmental program "Investing for the Future" (to Genoscreen), a grant from the European Commission Seventh Framework Program (FP7/2007-2013, to Genoscreen under grant agreement 278864 in the framework of the Patho-NGen-Trace project), grants from the Drug Resistant Tuberculosis Fund (R015833003, to Dr. Chaiprasert), the Faculty of Medicine, Siriraj Hospital, Mahidol University (to Dr. Chaiprasert), a grant from the Ministry of Economy and Competitiveness (MINECO), Spain (SAF2016-77346-R, to Dr. Comas), a grant from the European Research Council (638553-TB-ACCELERATE, to Dr. Comas), a grant from the BC Centre for Disease Control Foundation for Population and Public Health (to Dr. Gardy), a grant from the British Colombia Lung Association (to Dr. Gardy), grants from the Wellcome Trust and the Royal Society (101237/Z/13/Z and 102541/A/13/Z, to Drs. Wilson and Iqbal [Sir Henry Dale Fellows]), a grant from the National University of Singapore Yong Loo Lin School of Medicine Aspiration Fund (NUHSRO/2014/069/AF-New Idea/04, to Drs. Ong and Teo), a European Commission Seventh Framework Program European Genetic Network (EUROGEN) grant (201483, to Dr. Drobniewski), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to Dr. Rodwell). Dr. T. Walker is an NIHR Academic Clinical Lecturer, and Drs. Crook, Peto, and Caulfield are NIHR Senior Investigators. No potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Stéphanie Duthoy, Carina Hahn, Alamdar Hussain, Yannick Laurent, Mathilde Mairey, Vanessa Mohr, and Mahmood Qadir for technical assistance and George F. Gao, Director of the Chinese Center for Disease Control and Prevention, for directing the Chinese grant and sequencing program ; Peer reviewed
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) ; FINEP (Brazil) ; NSFC (China) ; CNRS/IN2P3 (France) ; BMBF (Germany) ; DFG (Germany) ; HGF (Germany) ; SFI (Ireland) ; INFN (Italy) ; NASU (Ukraine) ; STFC (UK) ; NSF (USA) ; BMWFW (Austria) ; FWF (Austria) ; FNRS (Belgium) ; FWO (Belgium) ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; MES (Bulgaria) ; CAS (China) ; MoST (China) ; COLCIENCIAS (Colombia) ; MSES (Croatia) ; CSF (Croatia) ; RPF (Cyprus) ; MoER (Estonia) ; ERC IUT (Estonia) ; ERDF (Estonia) ; Academy of Finland (Finland) ; MEC (Finland) ; HIP (Finland) ; CEA (France) ; GSRT (Greece) ; OTKA (Hungary) ; NIH (Hungary) ; DAE (India) ; DST (India) ; IPM (Iran) ; NRF (Republic of Korea) ; WCU (Republic of Korea) ; LAS (Lithuania) ; MOE (Malaysia) ; UM (Malaysia) ; CINVESTAV (Mexico) ; CONACYT (Mexico) ; SEP (Mexico) ; UASLP-FAI (Mexico) ; MBIE (New Zealand) ; PAEC (Pakistan) ; MSHE (Poland) ; NSC (Poland) ; FCT (Portugal) ; JINR (Dubna) ; MON (Russia) ; RosAtom (Russia) ; RAS (Russia) ; RFBR (Russia) ; MESTD (Serbia) ; SEIDI (Spain) ; CPAN (Spain) ; MST (Taipei) ; ThEPCenter (Thailand) ; IPST (Thailand) ; STAR (Thailand) ; NSTDA (Thailand) ; TUBITAK (Turkey) ; TAEK (Turkey) ; SFFR (Ukraine) ; DOE (USA) ; MPG (Germany) ; FOM (The Netherlands) ; NWO (The Netherlands) ; MNiSW (Poland) ; NCN (Poland) ; MEN/IFA (Romania) ; MinES (Russia) ; FANO (Russia) ; MinECo (Spain) ; SNSF (Switzerland) ; SER (Switzerland) ; Marie-Curie programme ; European Research Council ; EPLANET (European Union) ; Leventis Foundation ; A. P. Sloan Foundation ; Alexander von Humboldt Foundation ; Belgian Federal Science Policy Office ; Fonds pour la Formation a la Recherche dans l'Industrie et dans l'Agriculture (FRIABelgium) ; Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium) ; Ministry of Education, Youth and Sports (MEYS) of the Czech Republic ; Council of Science and Industrial Research, India ; Foundation for Polish Science ; European Union, Regional Development Fund ; Compagnia di San Paolo (Torino) ; Consorzio per la Fisica (Trieste) ; MIUR (Italy) ; Thalis programme ; Aristeia programme ; EU-ESF ; Greek NSRF ; National Priorities Research Program by Qatar National Research Fund ; EPLANET ; Marie Sklodowska-Curie Actions ; ERC (European Union) ; Conseil general de Haute-Savoie ; Labex ENIGMASS ; OCEVU ; Region Auvergne (France) ; XuntaGal (Spain) ; GENCAT (Spain) ; Royal Society (UK) ; Royal Commission for the Exhibition of 1851 (UK) ; MIUR (Italy): 20108T4XTM ; The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.
Background: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. Methods: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. Results: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. Conclusion: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.