The complete genome sequence of Escherichia coli EC958: a high quality reference sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131 clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage.

Global dissemination of a multidrug resistant Escherichia coli clone

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000–2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL–resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen.

Characterisation of a cell wall-anchored protein of Staphylococcus saprophyticus associated with linoleic acid resistance

The Gram-positive bacterium Staphylococcus saprophyticus is the second most frequent causative agent of community-acquired urinary tract infections (UTI), accounting for up to 20% of cases. A common feature of staphylococci is colonisation of the human skin. This involves survival against innate immune defenses including antibacterial unsaturated free fatty acids such as linoleic acid which act by disrupting bacterial cell membranes. Indeed, S. saprophyticus UTI is usually preceded by perineal skin colonisation.

Intersectionality, rural criminology, and re-imaging the boundaries of critical criminology

One of the significant shortcomings of the criminological canon, including its critical strands – feminist, cultural and green – has been its urbancentric bias. In this theoretical model, rural communities are idealised as conforming to the typical small-scale traditional societies based on cohesive organic forms of solidarity and close density acquaintance networks. This article challenges the myth that rural communities are relatively crime free places of ‘moral virtue’ with no need for a closer scrutiny of rural context, rural places, and rural peoples about crime and other social problems. This challenge is likewise woven into the conceptual and empirical narratives of the other articles in this Special Edition, which we argue constitute an important body of innovative work, not just for reinvigorating debates in rural criminology, but also critical criminology. For without a critical perspective of place, the realities of context are too easily overlooked. A new criminology of crime and place will help keep both critical criminology and rural criminology firmly anchored in the sociological and the criminological imagination. We argue that intersectionality, a framework that resists privileging any particular social structural category of analysis, but is cognisant of the power effects of colonialism, class, race and gender, can provide the theoretical scaffolding to further develop such a project.

Pharmacokinetics and tumor disposition of PEGylated, methotrexate conjugated poly-l-lysine dendrimers

Dendrimers have potential for delivering chemotherapeutic drugs to solid tumours via the enhanced permeation and retention (EPR) effect. The impact of conjugation of hydrophobic anticancer drugs to hydrophilic PEGylated dendrimer surfaces, however, has not been fully investigated. The current study has therefore characterised the effect on dendrimer disposition of conjugating α-carboxyl protected methotrexate (MTX) to a series of PEGylated 3H-labelled poly-L-lysine dendrimers ranging in size from generation 3 (G3) to 5 (G5) in rats. Dendrimers contained 50% surface PEG and 50% surface MTX. Conjugation of MTX generally increased plasma clearance when compared to conjugation with PEG alone. Conversely, increasing generation reduced clearance, increased metabolic stability and reduced renal elimination of the administered radiolabel. For constructs with molecular weights >20 kDa increasing the molecular weight of conjugated PEG also reduced clearance and enhanced metabolic stability but had only a minimal effect on renal elimination. Tissue distribution studies revealed retention of MTX conjugated smaller (G3-G4) PEG570 dendrimers (or their metabolic products) in the kidneys. In contrast, the larger G5 dendrimer was concentrated more in the liver and spleen. The G5 PEG1100 dendrimer was also shown to accumulate in solid Walker 256 and HT1080 tumours and comparative disposition data in both rats (1 to 2% dose/g in tumour) and mice (11% dose/g in tumour) are presented. The results of this study further illustrate the potential utility of biodegradable PEGylated poly-L-lysine dendrimers as long circulating vectors for the delivery and tumour-targeting of hydrophobic drugs.

Blended learning : meeting the needs of distance education students

This thesis involved research into the barriers and enablers that existed for a cohort of mature-aged education support students engaging with blended learning through distance education. The findings that emerged from this research indicated that a flexible model of blended learning is possible in this context. The findings shed light on the experiences of novice technology users' participation in blended learning. The study highlighted the significance of factors such as isolation, technology, communication, connectivity, prior learning, and the growth of self-efficacy that influenced learner engagement.

Media Arts should be at the core of the Australian Curriculum

The Final Report of the Review of the Australian Curriculum is seriously flawed. Many aspects of the report have attracted comment – but the recommendation that schools do away with a major, world-leading innovation has not. For the first time, Media Arts, one of the five strands of the Arts curriculum, was to become a compulsory subject for primary school students. This will no longer be the case if the Review’s recommendations are adopted by the government.

Metal Skin and the cinema of noise

In traditional communication and information theory, noise is the demon Other, an unwelcome disruption in the passage of information. Noise is "anything that is added to the signal between its transmission and reception that is not intended by the source...anything that makes the intended signal harder to decode accurately". It is in Michel Serres' formulation, the "third man" in dialogue who is always assumed, and whom interlocutors continually struggle to exclude. Noise is simultaneously a condition and a by-product of the act of communication, it represents the ever present possibility of disruption, interruption, misunderstanding. In sonic or musical terms noise is cacophony, dissonance. For economists, noise is an arbitrary element, both a barrier to the pursuit of wealth and a basis for speculation. For Mick (Jeremy Sims) and his mate Kev (Ben Mendelsohn) in David Caesar's Idiot Box (1996), as for Hando (Russell Crowe) and his gang of skinheads in Geoffrey Wright's Romper Stomper (1992), or Dazey (Ben Mendelsohn) and Joe (Aden Young) in Wright's Metal Skin (1994) and all those like them starved of (useful) information and excluded from the circuit - the information poor - their only option, their only point of intervention in the loop, is to make noise, to disrupt, to discomfort, to become Serres' "third man", "the prosopopoeia of noise" (5).

The effects of metabolic work rate and ambient environment on physiological tolerance times while wearing explosive and chemical personal protective equipment

This study evaluated the physiological tolerance times when wearing explosive and chemical (>35kg) personal protective equipment (PPE) in simulated environmental extremes across a range of differing work intensities. Twelve healthy males undertook nine trials which involved walking on a treadmill at 2.5, 4 and 5.5 km.h-1 in the following environmental conditions, 21, 30 and 37 °C wet bulb globe temperature (WBGT). Participants exercised for 60 min or until volitional fatigue, core temperature reached 39 °C, or heart rate exceeded 90% of maximum. Tolerance time, core temperature, skin temperature, mean body temperature, heart rate and body mass loss were measured. Exercise time was reduced in the higher WBGT environments (WBGT37of trials (85/108; 78.7%) were terminated due to participant’s heart rate exceeding 90% of their maximum. A total of eight trials (7.4%) lasted the full duration. Only nine (8.3%) trials were terminated due to volitional fatigue and six (5.6%) due to core temperatures in excess of 39 °C. These results demonstrate that physiological tolerance times are influenced by the external environment and workload, and that cardiovascular strain is the limiting factor to work tolerance when wearing this heavy multi layered PPE.

The Catlin Seaview Survey – kilometre-scale seascape assessment, and monitoring of coral reef ecosystems

1.Marine ecosystems provide critically important goods and services to society, and hence their accelerated degradation underpins an urgent need to take rapid, ambitious and informed decisions regarding their conservation and management. 2.The capacity, however, to generate the detailed field data required to inform conservation planning at appropriate scales is limited by time and resource consuming methods for collecting and analysing field data at the large scales required. 3.The ‘Catlin Seaview Survey’, described here, introduces a novel framework for large-scale monitoring of coral reefs using high-definition underwater imagery collected using customized underwater vehicles in combination with computer vision and machine learning. This enables quantitative and geo-referenced outputs of coral reef features such as habitat types, benthic composition, and structural complexity (rugosity) to be generated across multiple kilometre-scale transects with a spatial resolution ranging from 2 to 6 m2. 4.The novel application of technology described here has enormous potential to contribute to our understanding of coral reefs and associated impacts by underpinning management decisions with kilometre-scale measurements of reef health. 5.Imagery datasets from an initial survey of 500 km of seascape are freely available through an online tool called the Catlin Global Reef Record. Outputs from the image analysis using the technologies described here will be updated on the online repository as work progresses on each dataset. 6.Case studies illustrate the utility of outputs as well as their potential to link to information from remote sensing. The potential implications of the innovative technologies on marine resource management and conservation are also discussed, along with the accuracy and efficiency of the methodologies deployed.

The many meanings of live coding

The ten-year anniversary of TOPLAP presents a unique opportunity for reflection and introspection. In this essay we ask the question, what is the meaning of live coding? Our goal is not to answer this question, in absolute terms, but rather to attempt to unpack some of live coding's many meanings. Our hope is that by exploring some of the formal, embodied, and cultural meanings surrounding live-coding practice, we may help to stimulate a conversation that will resonate within the live-coding community for the next ten years