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Comparison of the in vitro antibacterial activity of Ramizol, fidaxomicin, vancomycin, and metronidazole against 100 clinical isolates of Clostridium difficile by broth microdilution
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available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyAntibiotic drug development remains a major challenge with few candidates in clinical development. Ramizol, a first-in-class styrylbenzene antibiotic, is under development for the treatment of Clostridium difficile associated disease. Here, we investigate the in vitro antibacterial activity of Ramizol in comparison to fidaxomicin, vancomycin and metronidazole against 100 clinical isolates of C. difficile by the broth microdilution method. We show there is no apparent impact of ribotype, toxin-production, or resistance to fidaxomicin, vancomycin or metronidazole on the activity of Ramizol. Moreover, we show Ramizol has a narrower MIC range translating to potentially better control over the therapeutic dose. Together, these results support the further development of Ramizol for the treatment of C. difficile associated disease.The authors acknowledge funding from Boulos & Cooper Pharmaceuticals for this research
Impacts of groundwater depth on regional scale soil gleyization under changing climate in the Poyang Lake Basin, China
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available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 24 month embargo from date of publication (November 2018) in accordance with the publisher’s archiving policyVarious natural and anthropogenic factors affect the formation of gleyed soil. It is a major challenge to identify the key hazard factors and evaluate the dynamic evolutionary process of soil gleyization at a regional scale under future climate change. This study addressed this complex challenge based on regional groundwater modelling for a typical agriculture region located in the Ganjiang River Delta (GRD) of Poyang Lake Basin, China. We first implemented in-situ soil sampling analysis and column experiments under different water depths to examine the statistical relationship between groundwater depth (GD) and gleyization indexes including active reducing substance, ferrous iron content, and redox potential. Subsequently, a three-dimensional groundwater flow numerical model for the GRD was established to evaluate the impacts of the historical average level and future climate change on vadose saturation and soil gleyization (averaged over 2016–2050) in the irrigated farmland. Three climate change scenarios associated with carbon dioxide emission (A1B, A2, and B1) were predicted by the ECHAM5 global circulation model published in IPCC Assessment Report (2007). The ECHAM5 outputs were applied to quantify the variation of groundwater level and to identify the potential maximum gleyed zones affected by the changes of meteorological and hydrological conditions. The results of this study indicate that GD is an indirect indicator for predicting the gradation of soil gleyization at the regional scale, and that the GRD will suffer considerable soil gleyization by 2050 due to fluctuations of the water table induced by future climate changes. Compared with the annually average condition, the climate scenario B1 will probably exacerbate soil gleyization with an 8.8% increase in total gleyed area in GRD. On average, the highly gleyed areas will increase in area by 29.7 km2, mainly on the riverside area, and the medium-slightly gleyed area will increase by 19.2 km2 in the middle region.This work was partially supported by the National Key R&D Program of China (No. 2016YFC0402800), the National Natural Science Foundation of China (Nos. 41772254, 41502226, and 41402198), and the Fundamental Research Funds for the Central Universities (No. 2018B18714). We are grateful to Jiangxi Institute of Survey and Design, who provides the detailed hydrogeological data of PLB for establishing three-dimensional groundwater flow model. Yun Yang gratefully acknowledges financial support from China Scholarship Council (CSC No. 201706715023) during the visit to National Centre for Groundwater Research and Training (NCGRT), Australia. Behzad Ataie-Ashtiani and Craig T. Simmons acknowledge support from the National Centre for Groundwater Research and Training, Australia
Insomnia and mortality: A meta-analysis
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available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (November 2018) in accordance with the publisher’s archiving policyThe purpose of this review was to evaluate the strength of evidence for a relationship between risk of mortality and frequent and ongoing insomnia using a meta-analytic strategy.
Seventeen studies, including a total of 36,938,981 individuals followed up for a mean of 11.6 y, reporting the investigation of the association between mortality and frequent (≥3 nights/wk), ongoing (≥1 mo) insomnia were identified.
There was no difference in the odds of mortality for those individuals with symptoms of insomnia when compared to those without symptoms (OR = 1.06, 95%CI = 0.61–1.84, p = .84). This finding was echoed in the assessment of the rate of mortality in those with and without symptoms of insomnia using the outcomes of multivariate models, with the most complete adjustment for potential confounders, as reported by the individual studies included in this meta-analysis (HR = 1.07, 95%CI = .96–.1.19, p = .22). Additional analyses revealed a tendency for an increased risk of mortality associated with hypnotic use.
The current evidence reinforces the use of cognitive therapy, within a CBTi framework, as a frontline non-pharmacological treatment for insomnia to reassure patients their longevity will not be impacted as a consequence of suffering from insomnia
A whole of systems approach to improved understanding of the environmental, economic and social values of a frontier marine oil and gas field: Establishment, success factors and lessons learnt
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This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2018) in accordance with the publisher’s archiving policyThe Great Australian Bight is one of Australia's most valuable marine ecosystems supporting globally significant populations of marine mammals, seabirds, and diverse and highly endemic benthic assemblages, as well as important fishing, aquaculture and ecotourism industries. The region is also considered a significant frontier for potential offshore petroleum resources and is actively being explored for oil and gas. The Great Australian Bight Research Program (GABRP) was an innovative, multi-year, $20 million, inter-disciplinary research collaboration involving BP Developments Australia (BP), CSIRO, the South Australian Research and Development Institute (SARDI), the University of Adelaide and Flinders University, that was developed in response to exploration activities in the region. The Program was the first large-scale, integrated study of the Great Australian Bight that involved more than 100 of Australia's leading scientists to generate a whole-of-system understanding of the region's environmental, economic and social values. We outline the processes to establish this strategic research collaboration, identify the key areas for success, and critically the lessons learned in order to guide future initiatives in regions open to exploration and development. As a result of the GABRP, there is now a legacy of data, information and models to inform future sustainable development in the Great Australian Bight; leading to the region now being one of the better understood deep water Australian marine systems
Advances in Carbon Nanotube n-type Doping: Methods, Analysis and Applications
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This author accepted manuscript is made available following 24 month embargo from date of publication (Oct 2017) in accordance with the publisher’s archiving policyGreat advances in semiconductor technologies continue to be made with the demand for cheap, non-toxic, easily processed and environmentally friendly technologies on the rise. Single-walled carbon nanotubes (SWCNTs) are viewed as a promising candidate that satisfies these criteria however proper doping of the SWCNTs to provide n-type behaviour has been a persistent issue. In recent years, great advances have been made in providing air stable and efficient n-type doping of SWCNTs. This review presents the most recent and promising methods of n-type doping SWCNTs highlighted for their simplicity and quality of electrical properties. The analysis and major applications of these semiconductors with a focus on thermoelectric devices and transistors are discussed
Dysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment. Validation in PCa cell lines revealed that AUY922 caused marked alterations to cell morphology, and suppressed cell motility and invasion compared to vehicle or 17-AAG, concomitant with dysregulation of key extracellular matrix proteins such as fibronectin (FN1). Interestingly, while the expression of FN1 was increased by AUY922, FN1 secretion was significantly decreased. This resulted in cytosolic accumulation of FN1 protein within late endosomes, suggesting that AUY922 disrupts vesicular secretory trafficking pathways. Depletion of FN1 by siRNA knockdown markedly reduced the invasive capacity of PCa cells, phenocopying AUY922. These results highlight a novel mechanism of action for AUY922 beyond its established effects on cellular mitosis and survival and, furthermore, identifies extracellular matrix cargo delivery as a potential therapeutic target for the treatment of aggressive PCa
Polysulfides made from re-purposed waste are sustainable materials for removing iron from water
No full textThis article is licensed under a Creative Commons Attribution 3.0 Unported Licence.Water contaminated with Fe3+ is undesirable because it can result in discoloured plumbing fixtures, clogging, and a poor taste and aesthetic profile for drinking water. At high levels, Fe3+ can also promote the growth of unwanted bacteria, so environmental agencies and water authorities typically regulate the amount of Fe3+ in municipal water and wastewater. Here, polysulfide sorbents—prepared from elemental sulfur and unsaturated cooking oils—are used to remove Fe3+ contaminants from water. The sorbent is low-cost and sustainable, as it can be prepared entirely from waste. The preparation of this material using microwave heating and its application in iron capture are two important advances in the growing field of sulfur polymers
To Issue a Firefly’s Glow: Wormhole Geographies and Positionality in Mohsin Hamid's The Reluctant Fundamentalist
Get PDFHamid’s novelistic project is a creative examination of the relationship between the micro movements of individuals and the macro processes of globalisation. The micro movements of individual human agents are related to their political being-in-the-world and their geographical location. Using Sheppard’s notion of 'wormhole travel', I examine how geographical location affects political agency. In particular, I employ the notion of 'positionality' to say something meaningful about the way location and connectivity of cities, global conglomerates, and populations, affect the ability to develop individual political agency in a globalised world. Hamid’s novel questions the popular notion that globalisation is an external factor, which affects everything from the way we conceive of planetary geography to national and global economies and social action as such. I argue that political agency in this novel involves an increase in ideologically-informed will to affect one’s life as a citizen, or, to use Hamid’s own metaphor, to an ability to create 'a firefly’s glow bright enough to transcend the boundaries of continents and civilizations'