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Contains fulltext : 291657.pdf (Publisher’s version ) (Open Access) BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p

A body of research has shown that there are linguistic differences in the way people with epilepsy talk about their seizures when compared to those with non-epileptic seizures. We extend this line of research by presenting the results of a phonetic analysis comparing speech samples from people with a confirmed diagnosis of epilepsy (7 patients), to those with a confirmed diagnosis of non-epileptic seizures (8 patients). Variables considered include features of pitch, intensity, duration and pausing in their responses to questions from a neurologist during medical history-taking. We find only limited evidence of differences between the two diagnostic groups (epilepsy vs. non-epileptic seizures). We discuss possible reasons for this lack of evidence.

Invasive trees are a major problem in South Africa. Many species are well established whereas others are still in the early stages of invasion. The management of invasive species is most cost effective at the early stages of invasion; it is thus essential to target and contain naturalizing invaders before they spread across the landscape. Multi-scale species distribution models (SDMs) provide useful insights to managers; they combine species-occurrence observations with climatic variables to predict potential distributions of alien species. Applying SDMs in human-dominated ecosystems is complicated because many factors associated with human actions interact in complex ways with climatic and edaphic factors to determine the potential suitability of sites for species. The aim of this study was to determine the degree to which a worldwide invader, A. altissima (Simaroubaceae) has occupied its potential range in South Africa, to identify areas at risk of future invasion. To do this we built a set of SDMs at both global and country scales using climatic, land use and human-footprint data. Climatic data best explained the distribution of A. altissima at the global scale whereas variables reflecting human-mediated disturbances were most influential at the national scale. Our analyses show the importance of human-mediated disturbances at a global scale and human occupancy at a country scale in determining the range limits of A. altissima. Populations of this tree species are already present in most parts of South Africa that are environmentally suitable for the species, and management actions need to focus on preventing increases in density in these areas.

Visual representations of acoustic data are becoming more common in Conversation Analysis (CA) and Interactional Linguistics (IL) research. This article provides a survey of visual representations of acoustic data in the journal Research on Language and Social Interaction. Shortcomings in their preparation and use are identified and discussed. Comparisons are made with visual representations prepared by expert phoneticians. Suggestions are made as to how visual representations could be prepared and used more effectively to support CA/IL researchers’ claims and to allow readers to independently verify them.

South Africa has a major problem with invasive plant species. Many species have long residence times, are well established, and have large invasive ranges, whereas others are still in the early stages of invasion. Predicting the full extent of invasions for species that have only recently started spreading is important for guiding management strategies. Ailanthus altissima is a widespread invasive species in many parts of the world. Although it has had a long residence time in South Africa, it is yet to replicate the extent of invasiveness and major impacts reported for the species in other parts of its adventive range. We mapped the countries in which A . altissima has been reported and evaluated the invasion status of the species in each (i.e. the position of the species on the introduction-naturalization-invasion continuum as conceptualized by Richardson and Pysek, 2012). We then mapped the current distribution in more detail for South Africa. The species is known to be present in at least 51 countries and is invasive in 23 countries. Ailanthus altissima is present in all South African provinces except Limpopo and is most common and abundant in the Western Cape, Gauteng, Eastern Cape, and the Free State. We applied species distribution modelling using global distribution data to determine parts of the world, and in particular regions within South Africa, that are climatically suitable for the species. Large parts of Africa are potentially invasible by this species. Seven regions in South Africa were identified as high-risk areas for invasion by A . altissima . The species is already far too widespread in South Africa for eradication at the national scale to be feasible. A national strategy for managing the species should focus on: 1) early detection and rapid response in areas identified as climatically suitable and where the species is not already present; and 2) local and regional-scale initiatives based on objective prioritization in terms of feasibility of management success and asset protection.

Techniques of conversation analysis are employed to reach a better understanding of the interactional competencies of young children. Drawing on audio–video recordings of mother–child interactions, this paper examines laughter by young children after questions by the child's mother. It is argued that by laughing the child is showing an orientation to the conditional relevance of a second pair part of an adjacency pair on the production of a first pair part. It is argued that possible bases for young children using laughter after a question are the child's inability to answer a question in full, and their unwillingness to do so. The children studied are in the second year of life and are making the transition from the single to multiword stage. All participants are native speakers of English and speak English throughout the recordings.

The diagnosis of Mild Cognitive Impairment (MCI) characterises patients at risk of dementia and may provide an opportunity for disease-modifying interventions. Identifying persons with MCI (PwMCI) from adults of a similar age without cognitive complaints is a significant challenge. The main aims of this study were to determine whether generic speech differences were evident between PwMCI and healthy controls (HC), whether such differences were identifiable in responses to recent or remote memory questions, and to determine which speech variables showed the clearest between-group differences. This study analysed recordings of 8 PwMCI (5 females, 3 males) and 14 HC of a similar age (8 females, 6 males). Participants were recorded interacting with an intelligent virtual agent: a computer-generated talking head on a computer screen which asks pre-recorded questions when prompted by the interviewee through pressing the next key on a computer keyboard. Responses to recent and remote memory questions were analysed. Mann-Whitney U tests were used to test for statistically significant differences between PwMCI and HC on each of 12 speech variables, relating to temporal characteristics, number of words produced and pitch. It was found that compared to HC, PwMCI produce speech for less time and in shorter chunks, they pause more often and for longer, take longer to begin speaking and produce fewer words in their answers. It was also found that the PwMCI and HC were more alike when responding to remote memory questions than when responding to recent memory questions. These findings show great promise and suggest that detailed speech analysis can make an important contribution to diagnostic and stratification systems in patients with memory complaints.

Background and Aims The causes of microscopic colitis are currently poorly understood. Previous reports have found clinical associations with coeliac disease and genetic associations at the human leukocyte antigen [HLA] locus on the ancestral 8.1 haplotype. We investigated pharmacological and genetic factors associated with microscopic colitis in the UK Biobank. Methods In total, 483 European UK Biobank participants were identified by ICD10 coding, and a genome-wide association study was performed using BOLT-LMM, with a sensitivity analysis performed excluding potential confounders. The HLA*IMP:02 algorithm was used to estimate allele frequency at 11 classical HLA genes, and downstream analysis was performed using FUMA. Genetic overlap with inflammatory bowel disease [Crohn’s disease and ulcerative colitis] was investigated using genetic risk scores. Results We found significant phenotypic associations with smoking status, coeliac disease and the use of proton-pump inhibitors but not with other commonly reported pharmacological risk factors. Using the largest sample size to date, we confirmed a recently reported association with the MHC Ancestral 8.1 Haplotype. Downstream analysis suggests association with digestive tract morphogenesis. By calculating genetic risk scores, we also report suggestive evidence of shared genetic risk with Crohn’s disease, but not with ulcerative colitis. Conclusions This report confirms the role of genetic determinants in the HLA in the pathogenesis of microscopic colitis. The genetic overlap with Crohn’s disease suggests a common underlying mechanism of disease.

The political economy of urban water management demands the interrogation of a highly socialised and engineered space. Many approaches are available to the researcher, yet they are often based on their own claims concerning the nature of society and space, which are contradictory and incommensurate with the next. This makes a synthesis of theory problematic, suggesting an ‘either/or’ decision to the researcher. This paper provides a critical genealogy of theoretical approaches to the political economy of urban water management and a framework through which their synthesis may be discussed. It employs a critical realist philosophy, mapping each approach to its respective ontological and epistemic grounding. A metaphorical ‘walk’ is then taken across the resulting map in order to provide a coherent and logical survey of theory. Finally, critical realism is employed to argue that struggles to synthesise theory are rooted in their competing ontological claims. Critical realism and in particular Bob Jessop’s Strategic Relational Approach are assessed as means of reconciling tensions uncovered during the walk.

Can very young children deploy laughter interactionally? Using data from video recordings of 52 interactions between six mothers and their young children, this article examines one particular kind of sequence in which interactionally ordered child laughter occurs. In that sequence, the young child commits some kind of potential transgression (e.g., breaking wind, standing on objects on the floor, or playing in a proscribed location). The child's mother then draws attention to the potential transgression in some way (e.g., by admonishing the child, requesting a change to the child's behavior, issuing a particular kind of child-directed gaze), thus treating the child's action as constituting a transgression. At some point following the potential transgression, the child laughs. What is shown is that even young children can fit their laughter to the ongoing interactional sequence. It is argued that the child's laughter provides for a display of affiliation from the mother.

Demand modelling plays a vital role in water resource management yet has rarely been critically reviewed. This paper adopts a critical realist framework for a historical analysis of demand modelling practices and their role in long-term water resource management in England and Wales from 1945 to 2010. It then focuses on recent domestic demand models in the English and Welsh private water sector. A critique of scientific realist assumptions regarding demand models is presented and the role of the current regulatory environment in encouraging a highly strategic use of demand models is discussed. Policy recommendations toward more effective modelling practices are made.

Since its inception in 1989, the private water sector of England and Wales has been enlisted as a centrepiece in debates concerning the merits of privatisation. Advocates point to increased environmental performance and increased investment. Critics note a significant retraction of the early free market aspirations and increasingly prescriptive regulation. However, market mechanisms and liberalisation are once again being emphasised in policy, reigniting the debate surrounding the commoditisation of water. This thesis engages directly and critically with Karen Bakker's 'Uncooperative Commodity' approach to the 'reregulation' of the industry, arguing its tenants must be adapted to accommodate these recent developments. While Bakker's earlier accounts of the reregulation of the water industry placed a great emphasis on the geography and biophysical properties of water, later work by both her and her contemporaries have developed more refined and socialised models of how water and society interact to produce temporary regularities in the material world. This thesis argues that an appropriate means of developing Bakker's original thesis would be a greater focus on socio-historical context when exploring the materiality of water, and hence the degree to which water may be transformed into a private commodity. Bob Jessop's Strategic Relational Approach (Jessop 2008) is deployed as a means of describing and relating: (1) the degree to which research can identify underlying mechanisms which govern the outcomes of attempts to commoditise water under capitalist modes of production, (2) the role of the state and politics in flanking or supporting the commoditisation of water and (3) the role of existing discursive-institutional structures in introducing path-dependencies and uneven power geometries which in turn effect the outcomes of collective action towards the commoditisation of water. The thesis documents historical developments in English and Welsh resource planning, regulation, and policy from 1945 to 2012 in order to explain the current structure of the industry, its response to water scarcity, and the origins of the current reform programme. It then focuses on the conflicts and tensions between actors in the industry generated by the current reform programme and their role in affecting the degree of success of the programme itself.

Linguists, and other analysts of discourse, regularly make appeal to affectual states in determining the meaning of utterances. We examine two kinds of sequence that occur in everyday conversation. The first involves one participant making an explicit lexical formulation of a co-participant's affectual state (e.g., ‘you sound happy’, ‘don't sound so depressed’). The second involves responses to ‘positive informings’ and ‘negative informings’. Through consideration of sequential organization, participant orientation, and phonetic detail, we suggest that the attribution of analytic categories of affect is problematic. We argue that phonetic characteristics which might be thought to be associated with affect may better be accounted for with reference to the management of particular sequential-interactional tasks. The finding that stance does not inhere in any single turn at talk or any single linguistic aspect leads us to suggest that future investigations into stance and affect will need to pay attention simultaneously to matters of both linguistic-phonetic and sequential organization.

An auspicious but unexplored environment for studying phonetic variation in naturalistic interaction is where two or more participants say the same thing at the same time. Working with a core dataset built from the multimodal Augmented Multi-party Interaction corpus, the principles of conversation analysis were followed to analyze the sequential organization of the talk and to explain the phonetic variation observed. Acoustic divergence and equivalence between simultaneous responses are described. Phonetic features discussed include duration and timing, pitch, loudness, and phonation type. The interactional factors that explain the acoustic divergences are established through turn-by-turn analysis and consideration of gaze direction and other visible features. It is argued that any research on phonetic variation in naturalistic talk that disregards the local organization of interaction will always be incomplete.

Repetition poses certain problems for pragmatics, as evidenced by Sperber and Wilson's claim that “the effects of repetition on utterance interpretation are by no means constant”. This is particularly apposite when we examine repetitions produced in naturally occurring talk. As part of an ongoing study of how phonetics relates to the dynamic evolution of meaning within the sequential organisation of talk-in-interaction, we present a detailed phonetic and pragmatic analysis of a particular kind of self-repetition. The practice of repetition we are concerned with exhibits a range of forms: “have another go tomorrow … have another go tomorrow”, “it might do … it might do”, “it's a shame … it's a shame”. The approach we adopt emphasises the necessity of exploring participants’ displayed understandings of pragmatic inferences and attempts not to prejudge the relevance of phonetic (prosodic) parameters. The analysis reveals that speakers draw on a range of phonetic features, including tempo and loudness as well as pitch, in designing these repetitions. The pragmatic function of repetitions designed in this way is to close sequences of talk. Our findings raise a number of theoretical and methodological issues surrounding the prosody–pragmatics interface and participants’ understanding of naturally occurring discourse.

The migration behaviour of americium through Boom Clay, which is rich in organic matter, has been investigated by complexing 241 Am with 14 C-labelled Boom Clay natural organic matter (NOM) and passing the resulting 241 Am- 14 CNOM through undisturbed Boom Clay cores contained in columns. In the presence of soluble organic matter, the total concentration of Am in solution increases several orders of magnitude above the solubility limit due to NOM complexation/colloids formation which could lead to an increased americium mobility in Boom Clay. The mobility of these complexes depends strongly on their stability and on their interaction with the solid phase (sorption, filtration, etc.). Upon contacting the 241 Am- 14 CNOM mobile complexes with Boom Clay, the major part of Am becomes almost instantaneously dissociated and immobilised, while only a small fraction persists as “stabilised complex” which migrates along with the mobile NOM. By increasing the travel time in the clay, the recovery of these complexes was observed to decrease. This decrease could be fitted to a first order kinetic model with a rate of 8 × 10 −8 s −1 indicating a slow dissociation of these “stabilised” mobile complexes.

Investigations into the management of turn-taking have typically focussed on pitch and other prosodic phenomena, particularly pitch-accents. Here, non-pitch phonetic features and their role in turn-taking are described. Through sustained phonetic and interactional analysis of a naturally occurring, 12-minute long telephone call between two adult speakers of British English, sets of talk-projecting and turn-projecting features are identified. Talk-projecting features include the avoidance of durational lengthening, articulatory anticipation, continuation of voicing, the production of talk in maximally close proximity to a preceding point of possible turn-completion, and the reduction of consonants and vowels. Turn-projecting features include the converse of each of the talk-projecting features, and two other distinct features: release of plosives at the point of possible turn-completion, and the production of audible outbreaths. We show that features of articulatory and phonatory quality and duration are relevant factors in the design and treatment of talk as talk- or turn-projective.

The empirical focus of this paper is a conversational turn-taking phenomenon in which conjunctions produced immediately after a point of possible syntactic and pragmatic completion are treated by co-participants as points of possible completion and transition relevance. The data for this study are audio-video recordings of 5 unscripted face-to-face interactions involving native speakers of US English, yielding 28 'trail-off' conjunctions. Detailed sequential analysis of talk is combined with analysis of visible features (including gaze, posture, gesture and involvement with material objects) and technical phonetic analysis. A range of phonetic and visible features are shown to regularly co-occur in the production of 'trail-off' conjunctions. These features distinguish them from other conjunctions followed by the cessation of talk. © SAGE Publications 2012.

There is a need to get to grips with the phonetic design of talk in its totality and without a separation of prosodic and non-prosodic aspects. Features of duration, phonation and articulation are all shown to be systematic features of rush-throughs, and bound up with the turn-holding function of the practice. Data are drawn from audio and video recordings made in a range of interactional settings, all involving speakers of English from the UK or the US. The paper concludes by reviewing some of the reasons why this holistic approach is desirable, namely: empirical findings, the parametric nature of speech, and a commitment to a mode of enquiry which takes seriously observable details of all kinds.

Golder Associates (UK) Ltd, in partnership with Serco Assurance (Serco), undertook targeted cone penetration testing (CPT) of a series of six parallel on-site burial trenches on a nuclear licensed site in the UK. The form and concentration of radioactive and chemical material within the trenches is unknown. CPT was used to confirm the location of the bund walls and to characterise the material within the trenches. The CPT technique involves hydraulically pushing rods fitted with specialist characterisation “cones” into the ground. CPT generates no solid or liquid waste, and allowed rapid investigation of the trenches and bunds while ensuring exposure of radiation and contamination to workers was kept to a minimum, or removed in entirety. As a result of the unknown nature of radiological contamination within the trenches and the potential of introducing contamination into the inside of the CPT truck, a purpose-built extraction rig was constructed to withdraw the CPT equipment from the ground. Extraction of the equipment assumed airborne radioactive contamination was a potential hazard. The CPT locations selected for the investigation were based on non-intrusive geophysical survey work and a radiation survey, which identified the approximate location of the trenches, anomalies within the material (e.g. metallic objects), and radiation hotspots. The results of the geophysical surveys were overlaid with the original as-built drawings of the trenches. During the investigation the following investigation cones were deployed: • Resistance/friction cone, which determines geology through measurement of the friction on the sleeve of the cone and resistance on the tip of the cone; this was used to investigate the geology of the bunds. • Total gamma cone, which was used to obtain total gamma radiation results (in counts per second); • Groundwater sampler (BAT Sampler™), which was used to obtain a water sample from beneath the trenches; • Video cone, which was used to obtain a visual recording of the material within the trenches; and • Conductivity cone, which was used to investigate the presence of and depth to bodies of water below ground level (e.g. perched water, regional groundwater). The investigation collected essential data from an area of the site that had not previously been investigated, while minimising potential radiological exposure to all workers, and producing no investigation-derived waste. The investigation therefore confirmed the efficacy of cone penetration testing as a valid site investigation technique in a high hazard area. The data acquired from the CPT investigation and geophysical investigation also allowed boreholes to be sited in the bund walls between the trenches. Siting of the boreholes was a major risk for the project and presented a significant potential hazard. Golder has successfully used CPT on nuclear sites in the UK: as an innovative site investigation technique to facilitate radiological characterisation of an area with variable ground conditions; to investigate organic solvent plumes; and for the installation of blind tubes as a way of conducting subsurface radiation surveys and as part of a leak detection system (work in progress in partnership with Serco).Copyright © 2009 by ASME

In everyday English conversation, talk can be produced such that it is simultaneously a grammatical ending of what precedes it, and a beginning of what follows (e.g. “that's what I’d like to have is a fresh one”). A range of features of phonetic design (including pitch, loudness, duration, and articulatory characteristics) are shown to be deployed in systematic ways in order to handle the dual tasks of avoiding the signaling of transition relevance at the end of the pivot, and marking out the fittedness of the pivot to both what precedes and what follows. Turns built with pivots are found to be most often engaged in assessing, enquiring, or reporting, though their more general application as a practice for the continuation of a turn past a point of possible syntactic and pragmatic completion is emphasized.

This paper represents part of the output of an ongoing study of clusters of phonetic parameters in the management of talk-in-interaction. Here we report on the sequential organisation and phonetic form of abrupt-joins. By abrupt-join we mean to adumbrate a complex of recurrent phonetic events which attend a point of possible turn-completion, and the beginning of an immediately subsequent turn-constructional unit (TCU) produced by that same speaker. In doing an abrupt-join, the speaker can be seen to preempt the transition relevance and interactional implicativeness of the first unit. The phonetic features which constitute this practice include duration, rhythm, pitch, loudness and articulatory characteristics of both the end of the first unit and the beginning of the second. Abrupt-joins are a resource used in the building of a particular kind of multi-unit turn, where each unit performs a discrete action with the abrupt-join marking the juncture between them, with the subsequent talk changing the sequential trajectory projectable from the talk leading up to the abrupt- join. One clear distributional pattern emerges from the data: abrupt-joins occur regularly in closing- relevant and topic-transition sequences.