Print and Refractory Concrete: new opportunities in scale, surface and durability.

The conference presentation will discuss a recent collaboration between artist printmaker Tracy Hill and ceramic researcher Dr Alasdair Bremner. The aim was to create large format 3D relief prints that retained a print quality, yet were rendered in a durable material. The presentation will discuss the compromises and opportunities that developed from the cross-disciplinary activity. Tracy has been developing a way of translating the marks from etched metal plates and silkscreen images onto the surface of cast plaster. The direct interaction with this surface and the relationship which resulted between the oil based ink of the etched plate and the surface layer of the water based ink laid down by the silk screen, offered many potential combinations, creating a versatile and unique medium that was printed, yet retained a relief surface. The disadvantage of this process was the fragility of the resulting works. A potential solution was to translate the process into ceramic. Alasdair’s research using castable refractory concrete to create large format architectural ceramics presented a way to achieve pieces that would have the scale and durability that was required. This industrial technology offers the opportunity to achieve the creation of objects that do not conform to some of the traditional limitations of conventional clay yet can make use of a range of ceramic surface treatments. The challenge of the project was to translate the techniques that Tracy had developed for use in plaster to refractory concrete material, combining the print quality with ceramic glaze qualities. They will discuss the processes developed and highlight the advantages print making in refractory concrete can offer in terms of the interaction of glaze and oxide; the scales possible and finally the durability and permanency. This collaboration opens up new possibilities for printmaking beyond the conventional print within a gallery space

Planning problems as types, plans as programs : a dependent types infrastructure for verification and reasoning about automated plans in Agda

Historically, the Artificial Intelligence and programming language fields have had a mutually beneficial relationship. Typically, theoretical results in the programming language field have practical utility in the Artificial Intelligence field. One example of this that has roots in both declarative languages and theorem proving is AI planning. In recent years, new programming languages have been developed that are founded on dependent type theory. These languages are not only more expressive than traditional programming languages but also have the ability to represent and prove mathematical properties within the language. This thesis will explore how dependently typed languages can benefit the AI planning field. On one side this thesis will show how AI planning languages can be enriched with more expressivity and stronger verification guarantees. On the other, it will show that AI planning is an ideal field to illustrate the practical utility of largely theoretical aspects of programming language theory. This thesis will accomplish this by implementing multiple inference systems for plan validation in the dependently-typed programming language Agda. Importantly, these inference systems will be automated, and embody the Curry-Howard correspondence where plans will not only be proof-terms but also executable functions. This thesis will then show how the dependently-typed implementations of the inference systems can be further utilised to add enriched constraints over plan validation

A transmission model for Salmonella in grower-finisher pigs

This paper presents a model describing the dynamic transmission of Salmonella Typhimurium between pigs on a typical, British pig grower-finisher farm. A modified Reed-Frost discrete-time model was used to estimate the probability of infection for susceptible pigs

Opening the Woods: Towards a Quantification of Neolithic Clearance Around the Somerset Levels and Moors

Environmental reconstructions from pollen records collected within archaeological landscapes have traditionally taken a broadly narrative approach, with few attempts made at hypothesis testing or formal assessment of uncertainty. This disjuncture between the traditional interpretive approach to palynological data and the requirement for detailed, locally specific reconstructions of the landscapes in which people lived has arguably hindered closer integration of palaeoecological and archaeological datasets in recent decades. Here we implement a fundamentally different method for reconstructing past land cover from pollen records to the landscapes of and around the Somerset Levels and Moors — the Multiple Scenario Approach (MSA) — to reconstruct land cover for a series of 200-year timeslices covering the period 4200–2000 cal BC. Modelling of both archaeological and sediment chronologies enables integration of reconstructed changes in land cover with archaeological evidence of contemporary Neolithic human activity. The MSA reconstructions are presented as a series of land cover maps and as graphs of quantitative measures of woodland clearance tracked over time. Our reconstructions provide a more nuanced understanding of the scale and timing of Neolithic clearance than has previously been available from narrative based interpretations of pollen data. While the archaeological record tends to promote a view of long-term continuity in terms of the persistent building of wooden structures in the wetlands, our new interpretation of the palynological data contributes a more dynamic and varying narrative. Our case study demonstrates the potential for further integration of archaeological and palynological datasets, enabling us to get closer to the landscapes in which people lived

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM):pragmatic, parallel group, open label, randomised controlled trial

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Unknow

Identification of Novel Antimalarial Chemotypes via Chemoinformatic Compound Selection Methods for a High-Throughput Screening Program against the Novel Malarial Target, PfNDH2: Increasing Hit Rate via Virtual Screening Methods

Malaria is responsible for approximately 1 million deaths annually; thus, continued efforts to discover new antimalarials are required. A HTS screen was established to identify novel inhibitors of the parasite's mitochondrial enzyme NADH:quinone oxidoreductase (PfNDH2). On the basis of only one known inhibitor of this enzyme, the challenge was to discover novel inhibitors of PfNDH2 with diverse chemical scaffolds. To this end, using a range of ligand-based chemoinformatics methods, ~17000 compounds were selected from a commercial library of ~750000 compounds. Forty-eight compounds were identified with PfNDH2 enzyme inhibition IC(50) values ranging from 100 nM to 40 μM and also displayed exciting whole cell antimalarial activity. These novel inhibitors were identified through sampling 16% of the available chemical space, while only screening 2% of the library. This study confirms the added value of using multiple ligand-based chemoinformatic approaches and has successfully identified novel distinct chemotypes primed for development as new agents against malaria

Transcriptional Infidelity Promotes Heritable Phenotypic Change in a Bistable Gene Network

Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms. Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise. It is becoming clear that noise in gene expression can influence cell fate. Although the origins and consequences of noise have been studied, the stochastic and transient nature of RNA errors during transcription has not been considered in the origin or modeling of noise nor has the capacity for such transient errors in information transfer to generate heritable phenotypic change been discussed. We used a classic bistable memory module to monitor and capture transient RNA errors: the lac operon of Escherichia coli comprises an autocatalytic positive feedback loop producing a heritable all-or-none epigenetic switch that is sensitive to molecular noise. Using single-cell analysis, we show that the frequency of epigenetic switching from one expression state to the other is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases or to the absence of auxiliary RNA fidelity factors GreA and GreB (functional analogues of eukaryotic TFIIS). Therefore, transcription infidelity contributes to molecular noise and can effect heritable phenotypic change in genetically identical cells in the same environment. Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour