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- Sartelli, Massimo, et al.
(author)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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In: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Research review (peer-reviewed)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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- Tosh, Kerrie, et al.
(author)
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Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa
- 2006
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:27, s. 10364-10368
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Journal article (peer-reviewed)abstract
- The sst1 locus has been identified in a mouse model to control resistance and susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have now identified Ipr1 (intracellular pathogen resistance 1) to be the gene responsible. Ipr1 is encoded within the sst1 locus and is expressed in the tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1-susceptible mice. We have therefore examined the closest human homologue of Ipr1, SP110, for its ability to control susceptibility to M. tuberculosis infection in humans. In a study of families from The Gambia we have identified three polymorphisms that are associated with disease. On examination of additional families from Guinea-Bissau and the Republic of Guinea, two of these associations were independently replicated. These variants are in strong linkage disequilibrium with each other and lie within a 31-kb block of low haplotypic diversity, suggesting that a polymorphism within this region has a role in genetic susceptibility to tuberculosis in humans.
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- Barack, Leor, et al.
(author)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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In: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Research review (peer-reviewed)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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- Cooke, Graham S, et al.
(author)
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Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis
- 2006
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In: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 174:3, s. 339-343
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Journal article (peer-reviewed)abstract
- RATIONALE: Interferon-gamma (IFN-gamma) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-gamma signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear. METHODS: A total of 1,301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding IFN-gamma and its receptor subunits (IFNG, IFNGR1, and IFNGR2). RESULTS: Within the IFNG gene, two promoter variants showed evidence of novel disease association: -1616GG (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.11-2.00; p = 0.008) and +3234TT (OR, 1.40; 95% CI, 1.09-1.80; p = 0.009). The +874AA genotype was not significantly more frequent among cases over control subjects (OR, 1.16; 95%CI, 0.89-1.51; p = 0.25). In addition, novel disease association was also found with the -56CC genotype of the IFNGR1 promoter (OR, 0.75; 95% CI, 0.57-0.99; p = 0.041). No disease association was seen with the IFNGR2 locus. CONCLUSIONS: These results provide evidence of a significant role for genetic variation at the IFNG locus and provide detailed understanding of the genetic mechanisms underlying this association. The disease association with IFNGR1 is novel, and together these findings support the hypothesis that genetically determined variation in both IFN-gamma production and responsiveness influences the risk of developing tuberculosis.
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