The anti-virulence effect of cranberry active compound proanthocyanins (PACs) on the expression of genes in the third-generation cephalosporin-resistant Escherichia coli CTX-M-15 associated with urinary tract infection.

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Beta-lactam resistant urinary tract infections: prevalence, the development of rapid diagnostics and novel treatments

Background The 21st century has seen antibiotic resistance rise to be a major public health concern. The O’Neill report in 2016 reiterated the importance of antibiotic resistance and proposed many actions, including strengthening surveillance systems, the development of rapid diagnostics, and investment in new classes of antibiotics and alternatives. Urinary tract infections (UTIs) are one of the most common infections diagnosed in the United Kingdom with uropathogenic Escherichia coli (UPEC) the most common cause. It is thought that the main reason why UPEC is so successful at causing UTIs, is its expression of a wide range of virulence factors including adhesins, capsules, toxins and iron-acquisition systems. Overuse of beta-lactam antibiotics to treat UTIs has led to selection for extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae, a major cause of antibiotic resistant urinary tract infections (UTIs). The prevalence of ESBL producing UTIs has dramatically risen, limiting treatment options. The most common ESBL types seen today are CTX-M, TEM, OXA and SHV. The emergence and spread of these types of ESBLs is thought to be through the horizontal transmission of antibiotic resistance plasmids IncL/M, IncF, IncN and IncI1. These conjugative plasmids have been directly linked to major outbreaks of antibiotic resistance. Standard detection methods for ESBL-producing UTIs are time-consuming, with disputed accuracy. Patients are often treated empirically with broad-spectrum antibiotics. Reducing the time spent on broad-spectrum antibiotics by prescribing a more appropriate treatment, increases the favorability of the outcome of the patient and shortens the stay in hospital. Aims This study had three aims: to investigate the prevalence of ESBLs and the relationship between plasmids and ESBLs in Leicestershire; to develop a rapid, accurate method to detect ESBLs (TEM, SHV, OXA, and CTX-M) using real-time PCR and to investigate the effect of cranberry (Cysticlean®) on the expression of 10 virulence genes. Methods A total of 236 uropathogenic E. coli ESBL-producing isolates were collected from the Leicester Royal Infirmary. This study identified ESBL genes (CTX-M, SHV, TEM and OXA) and multiple CTX-M gene subtypes by multiplex PCR. A multiplex PCR-based replicon typing assay identified IncFIA, IncI1, IncL/M, IncN and IncFII. A real-time PCR assay was designed using amplicon melting analysis and the Plexor system to detect the ESBL family. A CTX-M-producing E.coli isolate was treated with the cranberry extract Cysticlean®. Taqman qRT-PCR was used to detect the relative expression of the virulence genes SAT, USP, ChuA, SoxS, KPSM, TraT, RecA, IdfB and HcaT and the antibiotic resistance gene CTX-M. Results ESBL genes were identified as follows: CTX-M (71.6%), OXA (7.6%), TEM (3.8%) and SHV (3.8%) with multiple genes detected in 10.2% of isolates. CTX-M-1 (84.1%) was the most frequently detected CTX-M subtype. Replicon typing results were as follows: IncL/M (29.2%), IncN (14.4%), IncI1 (5.1%), IncFII (27.5%) and IncFIA (23.3%). A combination of IncL/M, IncFII and IncFIA was the most common at 9.8%. A positive correlation between CTX-M and all plasmids except IncI1 was found. The qualitative real-time PCR assay correctly identified 97.7% isolates tested, with a sensitivity and specificity of 98.7% and 83.3% respectively. The positive predictive value was 97.5% and the negative predictive value was 90.9%. Results from the qRT-PCR assay showed that Cysticlean® was able to significantly reduce the expression of all the genes investigated. Conclusions This is the first study to analyse the prevalence of uropathogenic ESBLs in Leicestershire. The ability to rapidly and accurately detect ESBL genes is an important step in improving antimicrobial stewardship and reducing morbidity and mortality as a result of ESBL-producing pathogenic infections. The ability to reduce the expression of critical virulence factors, could lead to the development of alternatives to antibiotics

How the Trans Pacific Partnership Agreement could undermine PHARMAC and threaten access to affordable medicines and health equity in New Zealand

New Zealand\u27s Pharmaceutical Management Agency (PHARMAC) has been highly successful in facilitating affordable access to medicines through a combination of aggressive price negotiations, innovative procurement mechanisms, and careful evaluation of value for money. Recently the US government, through the establishment of a series of bilateral and plurilateral “free” trade agreements, has attempted to constrain the pharmaceutical access programs of other countries in order to promote the interests of the pharmaceutical industry. The Trans Pacific Partnership Agreement (TPPA) represents the latest example; through the TPPA the US is seeking to eliminate therapeutic reference pricing, introduce appeals processes for pharmaceutical companies to challenge formulary listing and pricing decisions, and introduce onerous disclosure and “transparency” provisions that facilitate industry involvement in decision-making around coverage and pricing of medicines (and medical devices). This paper argues that the US agenda, if successfully prosecuted, would be likely to increase costs and reduce access to affordable medicines for New Zealanders. This would in turn be likely to exacerbate known inequities in access to medicines and thus disproportionately affect disadvantaged population groups, including Māori and Pacific peoples

The Use of Matrix Technique in an Analysis of Atta Personal Pronouns

All Philippine languages have multiple pronoun sets, differing in distribution within the clause, and differing in internal complexity. Traditionally, pronoun sets have been listed and their distribution stated, but few attempts have been made to describe their internal structuring. Smearing of morpheme boundaries has made conventional morpheme analysis of the pronouns a difficult and often unproductive exercise. It will be demonstrated in this paper, however, that by using the techniques of matrix permutation and conflation, the ranking of pronouns and a display of their internal structure is entirely possible. The purpose of this paper is, first, to demonstrate how this was accomplished for the Atta pronouns, and second, to show how on the basis of these matrices meanings can be attributed to each of the pronoun formatives

Chemical stratification of the crust : isotope, trace element, and major element constraints from crustally contaminated lavas and lower crustal xenoliths

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric and Planetary Sciences, 1987.Microfiche copy available in Archives and Science.Includes bibliographies.by Mary Ruth Reid.Ph.D

A Multiple case study of college first-year seminars

John N. Gardner in 1972 advocated a new concept called the first-year seminar to increase academic performance and retention for freshmen students. The term first-year seminar defined a fairly diverse instructional construct, but the goal was clear and focused. It was to improve student retention rates. Research trends indicated a positive and almost always statistically significant relationship between first-year seminar participation and college achievement and higher persistence rates. Existing studies reflected a variety of significant methodological issues. Also; few cross-institutional research studies were reported and far fewer considered the content of the construct called a first-year seminar. The purpose of this investigation was to address these shortfalls by defining the multiple dimensions of first-year seminars and a prescription for future success. Case study methodology was used to investigate the process aspects of first-year seminar programs at three different institutional sites. The sites selected were research universities in the southeastern United States, the Rocky Mountains, and the southwestern United States. Results suggested that first-year seminar programs were very diverse across the three campuses. For example, two course designators were used to identify three different types of courses at the Rocky Mountain institution. Senior faculty members were the preferred instructors. The southeastern site had a dedicated management structure and course identifier, published the primary textbook, established well-defined instructional requirements, and hired the course\u27s instructors from across the campus. These instructors were drawn predominately from the institution\u27s professional staff. The southwestern institution\u27s program rested upon the rise and fall of independent instructional efforts within several different Colleges. Instructors varied and ranged from graduate students to staff members to faculty. A multitude of reasons were identified for why a seminar should be established, but student retention was one of the least cited reasons. The evidence indicated the cases shared some inter-site and intra-site commonalities and differences in their expectations and courses. The cases emphasized, either directly or indirectly, one or more aspects associated with students\u27 development of self-regulation. This emphasis on self-regulatory strategies suggests a different theoretical basis for first-year seminars. A first-year seminar model based on the social-cognitive perspective of self-regulation is proposed

Fire performance of Fibre Reinforced Polymer (FRP) bars in reinforced concrete: an experimental approach

During the past two decades, Fibre Reinforced Polymer (FRP) bars have been applied as viable alternatives to internal steel reinforcement of concrete, owing to their numerous benefits over steel reinforcement including comparatively high tensile strength and non-corrosive properties. However, there are limitations on the use of FRP as reinforcement, where fire resistance of structures is required, due to a lack of understanding of the behaviour of FRP materials at elevated temperature. This hinders application of FRP materials in many cases. To understand the complexities of FRP bars’ response at elevated temperature, this thesis examines current design guidance and literature to highlight gaps in understanding. The experimental work within the thesis focusses on three commercially available FRP bars; two Glass FRP (GFRP) bars and one Carbon FRP (CFRP) bar. Bench-scale characterisation tests using Dynamic Mechanical analysis (DMA) and Thermogravimetric analysis (TGA) have been performed to understand the deterioration of FRP bars at elevated temperature. The experimental work has defined a glass transition (Tg) and decomposition temperature (Td) range for each of the FRP bars. Using the results from the bench-scale characterisation tests and direct tensile tests, a novel predictive model for the reduction in tensile strength of FRP materials at high temperature has been proposed. A study on the bond capacity of fibre reinforced polymer (FRP) bars in concrete at elevated temperature demonstrated the requirement for cold anchorage of the reinforcement. To further determine the impact of cold anchorage on FRP reinforced concrete (RC) beams, tests were carried out with both continuous and lap spliced FRP at ambient temperature and under sustained load with transient localised heating. Cold anchorage of the reinforcement was maintained throughout testing and confirmed with local temperature measurements. The results demonstrate that cold anchorage (i.e. maintained below the onset of the glass transition range) of FRP bars is necessary to ensure their safe use as internal reinforcement in concrete, unless unrealistically deep concrete cover is provided. Cold anchorage may be provided in a number of ways; continuity of reinforcement across compartments, bent bars in the anchorage zone or increased concrete cover at anchorage zones. Where this is provided the performance of FRP bars is demonstrated – for the particular conditions of the current study – to be satisfactory under full service loads and at reinforcement temperatures exceeding the decomposition of the polymer matrix (>380°C for the bars in the current study). The research has identified a minimum suite of tests necessary to characterize thermo-mechanical behaviour of proprietary FRP bars. By understanding the effects of temperature on the polymer resin matrix and on the FRPs’ tensile and bond properties, and by rationally optimizing the placement and anchorage of the bars, this thesis has demonstrated FRP reinforcements may be designed as fire-safe alternatives to steel reinforcement for concrete

Overstory and understory vegetation interact to alter soil community composition and activity

Aim: To test if there is an interactive effect between tree and understory species on the soil microbial community (SMC), community level physiological profiles (CLPP) and soil micro-fauna. Method: A replicate pot experiment with five sapling tree species (Betula pendula, Betula pubescens, Sorbus aucuparia, Quercus petraea and Pinus sylvestris) and a no-tree treatment with and without Calluna vulgaris was established. After 21 months samples were taken for phospholipid fatty acid (PLFA) analysis, CLPP and soil microfauna assessment. Results: There was an interactive effect of tree species and Calluna on the SMC, CLPP and nematode densities. Calluna addition changed the SMC composition (increase in fungal PLFAs) and the CLPP (lower utilisation of most carbon sources but greater utilisation of phenolic acids). A multivariate test for homogeneity of dispersion showed that while Calluna addition resulted in the presence of an altered microbial composition, it did not result in there being less variability among the samples with Calluna than among the samples without Calluna. Sapling trees with Calluna present grew less well than trees without Calluna. Structural equation modelling showed that it is possible that Calluna had an indirect effect on the SMC via below-ground tree biomass as well as a direct effect. Conclusion: Interactions between trees and understory vegetation can impact on the composition of soil biota and their activity