Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

A phase II study of glembatumumab vedotin for metastatic uveal melanoma

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease \u3e100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release

FAIR Data Pipeline: provenance-driven data management for traceable scientific workflows

Modern epidemiological analyses to understand and combat the spread of disease depend critically on access to, and use of, data. Rapidly evolving data, such as data streams changing during a disease outbreak, are particularly challenging. Data management is further complicated by data being imprecisely identified when used. Public trust in policy decisions resulting from such analyses is easily damaged and is often low, with cynicism arising where claims of "following the science" are made without accompanying evidence. Tracing the provenance of such decisions back through open software to primary data would clarify this evidence, enhancing the transparency of the decision-making process. Here, we demonstrate a Findable, Accessible, Interoperable and Reusable (FAIR) data pipeline developed during the COVID-19 pandemic that allows easy annotation of data as they are consumed by analyses, while tracing the provenance of scientific outputs back through the analytical source code to data sources. Such a tool provides a mechanism for the public, and fellow scientists, to better assess the trust that should be placed in scientific evidence, while allowing scientists to support policy-makers in openly justifying their decisions. We believe that tools such as this should be promoted for use across all areas of policy-facing research

Morality and progress:IR narratives on international revisionism and the status quo

Scholars debate the ambitions and policies of today’s ‘rising powers’ and the extent to which they are revising or upholding the international status quo. While elements of the relevant literature provide valuable insight, this article argues that the concepts of revisionism and the status quo within mainstream International Relations (IR) have always constituted deeply rooted, autobiographical narratives of a traditionally Western-dominated discipline. As ‘ordering narratives’ of morality and progress, they constrain and organize debate so that revisionism is typically conceived not merely as disruption, but as disruption from the non-West amidst a fundamentally moral Western order that represents civilizational progress. This often makes them inherently problematic and unreliable descriptors of the actors and behaviours they are designed to explain. After exploring the formations and development of these concepts throughout the IR tradition, the analysis is directed towards narratives around the contemporary ‘rise’ of China. Both scholarly and wider political narratives typically tell the story of revisionist challenges China presents to a US/Western-led status quo, promoting unduly binary divisions between the West and non-West, and tensions and suspicions in the international realm. The aim must be to develop a new language and logic that recognize the contingent, autobiographical nature of ‘revisionist’ and ‘status quo’ actors and behaviours

Crop Updates 2002 - Oilseeds

This session covers twenty seven papers from different authors: 1. Forward and acknowledgements, Dave Eksteen, ACTING MANAGER OILSEEDS PRODUCTIVITY AND INDUSTRY DEVELOPMENT Department of Agriculture PLENARY SESSION 2. GMO canola - Track record in Canada, K. Neil Harker and George W. Clayton,Agriculture and Agri-Food Canada, Lacombe Research Centre, Lacombe, Alberta, R. Keith Downey, Agriculture and Agri-Food Canada, Saskatoon Research Centre, Saskatoon, Saskatchewan 3. GMO canola – Prospects in Western Australia farming systems, Keith Alcock, Crop Improvement Institute, Department of Agriculture 4. Diamondback moth (DBM) in canola, Kevin Walden, Department of Agriculture CANOLA AGRONOMY 5. Getting the best out of canola in the low rainfall central wheatbelt, Bevan Addison and Peter Carlton, Elders Ltd 6. Canola variety performance in Western Australia, Kevin Morthorpe, Stephen Addenbrooke and Alex Ford, Pioneer Hi-Bred Australia P/L 7. Relative performance of new canola varieties in Department of Agriculture variety trials in 2000 and 2001, S. Hasan Zaheer, GSARI, Department of Agriculture, G. Walton, Crop Improvement Institute, Department of Agriculture 8. Which canola cultivar should I sow? Imma Farré, CSIRO Plant Industry, Floreat, Bill Bowden,Western Australia Department of Agriculture 9. The effect of seed generation and seed source on yield and quality of canola, Paul Carmody, Department of Agriculture 10. The accumulation of oil in Brassica species, J.A. Fortescue and D.W. Turner, Plant Biology, Faculty of Natural and Agricultural Sciences, The University of Western Australia, B. Tan, PO Box 1249, South Perth 11. Potential and performance of alternative oilseeds in WA, Margaret C. Campbell, Centre for Legumes in Mediterranean Agriculture 12. Comparison of oilseed crops in WA, Ian Pritchard and Paul Carmody, Department of Agriculture, Centre for Cropping Systems, Margaret Campbell, Centre for Legumes in Mediterranean Agriculture 13. Identifying constraints to canola production, Dave Eksteen, Canola Development Officer, Department of Agriculture 14. Boron – should we be worried about it? Richard W. BellA, K. FrostA, Mike WongB, and Ross BrennanC , ASchool of Environmental Science, Murdoch University, BCSIRO Land and Water, CDepartment of Agriculture PEST AND DISEASE 15. Yield losses caused when Beet Western Yellows Virus infects canola, Roger Jones and Jenny Hawkes, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture 16. Influence of climate on aphid outbreaks and virus epidemics in canola, Debbie Thackray, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Department of Agriculture 17. The annual shower of blackleg ascospores in canola: Can we predict and avoid it? Moin U. Salam, Ravjit K. Khangura, Art J. Diggle and Martin J. Barbetti, Department of Agriculture 18. Environmental influences on production and release of ascospores of blackleg and their implications in blackleg management in canola, Ravjit K. Khangura, Martin J. Barbetti , Moin U. Salam and Art J. Diggle, Department of Agriculture 19. WA blackleg resistance ratings on canola varieties form 2002, Ravjit Khangura, Martin J. Barbetti and Graham Walton, Department of Agriculture 20. Bronzed field beetle management in canola, Phil Michael, Department of Agriculture 21. DBM control in canola: Aerial versus boom application, Paul Carmody, Department of Agriculture 22. Effect of single or multiple spray trearments on the control of Diamondback moth (Plutella xylostella) and yield of canola at Wongan Hills, Françoise Berlandier, Paul Carmody and Christiaan Valentine, Department of Agriculture ESTABLISHMENT 23. GrainGuardÔ - A biosecurity plan for the canola industry, Greg Shea, Department of Agriculture 24. Large canola seed is best, particularly for deep sowing, Glen Riethmuller, Rafiul Alam, Greg Hamilton and Jo Hawksley, Department of Agriculture 25. Canola establishment with seed size, tines and discs, with and without stubble, Glen Riethmuller, Rafiul Alam, Greg Hamilton and Jo Hawksley, Department of Agriculture WEEDS 26. Role of Roundup ReadyÒ canola in the farming system, Art Diggle1, Patrick Smith2, Paul Neve3, Felicity Flugge4, Amir Abadi5, Stephen Powles3 1Department of Agriculture, 2CSIRO, Sustainable Ecosystems, 3Western Australian Herbicide Resistance Initiative, University of Western Australia, 4Centre for Legumes in Mediterranean Agriculture, University of Western Australia, 5Touchstone Consulting, Mt Hawthorn FEED 27. Getting value from canola meals in the animal feed industries: Aquaculture, Brett Glencross and John Curnow, Department of Fisheries - Government of Western Australia and Wayne Hawkins, Department of Agricultur

Predicting Functional Alternative Splicing by Measuring RNA Selection Pressure from Multigenome Alignments

High-throughput methods such as EST sequencing, microarrays and deep sequencing have identified large numbers of alternative splicing (AS) events, but studies have shown that only a subset of these may be functional. Here we report a sensitive bioinformatics approach that identifies exons with evidence of a strong RNA selection pressure ratio (RSPR) —i.e., evolutionary selection against mutations that change only the mRNA sequence while leaving the protein sequence unchanged—measured across an entire evolutionary family, which greatly amplifies its predictive power. Using the UCSC 28 vertebrate genome alignment, this approach correctly predicted half to three-quarters of AS exons that are known binding targets of the NOVA splicing regulatory factor, and predicted 345 strongly selected alternative splicing events in human, and 262 in mouse. These predictions were strongly validated by several experimental criteria of functional AS such as independent detection of the same AS event in other species, reading frame-preservation, and experimental evidence of tissue-specific regulation: 75% (15/20) of a sample of high-RSPR exons displayed tissue specific regulation in a panel of ten tissues, vs. only 20% (4/20) among a sample of low-RSPR exons. These data suggest that RSPR can identify exons with functionally important splicing regulation, and provides biologists with a dataset of over 600 such exons. We present several case studies, including both well-studied examples (GRIN1) and novel examples (EXOC7). These data also show that RSPR strongly outperforms other approaches such as standard sequence conservation (which fails to distinguish amino acid selection pressure from RNA selection pressure), or pairwise genome comparison (which lacks adequate statistical power for predicting individual exons)

A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites

Background: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event. Results: microRNAs differentially expressed during the early post-infective stages of Brugia pahangi L3 were identified by microarray analysis. One of these, bpa-miR-5364, was selected for further study as it is upregulated ~12-fold at 24 hours post-infection, is specific to clade III nematodes, and is a novel member of the let-7 family, which are known to have key developmental functions in the free-living nematode Caenorhabditis elegans. Predicted mRNA targets of bpa-miR-5364 were identified using bioinformatics and comparative genomics approaches that relied on the conservation of miR-5364 binding sites in the orthologous mRNAs of other filarial nematodes. Finally, we confirmed the interaction between bpa-miR-5364 and three of its predicted targets using a dual luciferase assay. Conclusions: These data provide new insight into the molecular mechanisms underpinning the transmission of third stage larvae of filarial nematodes from vector to mammal. This study is the first to identify parasitic nematode mRNAs that are verified targets of specific microRNAs and demonstrates that post-transcriptional control of gene expression via stage-specific expression of microRNAs may be important in the success of filarial infection

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. OBJECTIVES: To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and risk of bias and extracted data. MAIN RESULTS: We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. AUTHORS' CONCLUSIONS: The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment

La Grange Comprehensive Plan 2018 - 2038

In the Fall of 2017, the City of La Grange and Texas Target Communities partnered to create a task force to represent the community. The task force was integral to the planning process, contributing the thoughts, desires, and opinions of community members—as well as their enthusiasm about La Grange’s future. This fifteen-month planning process ended in August 2018. The result of this collaboration is the La Grange Comprehensive Plan, which is the official policy guide for the community’s growth over the next twenty years.La Grange Comprehensive Plan 2018 - 2038 provides a guide for the future growth of the City. This document was developed by Texas Target Communities in partnership with the City of La Grange.Texas Target Communitie

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys