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Contributing to conversation analytic research into ‘atypical interaction’ (i.e. naturally-occurring interactions involving one or more participants with a communication disorder), this paper focuses on talk by individuals who present with both aphasic (language) impairments and other communicative impairments (motor, motor programming or cognitive in nature). It shows how, in three such cases, the co-occurring impairments may each contribute to turns at talk by the atypical speaker which are particularly problematic in terms of their understandability. In each case these trouble source turns result in (1) the production of other-initiations of repair by the recipient which are ‘off track’, and (2) repair sequences which are notably prolonged. This type of investigation fills a gap in existing atypical interaction research where most analysis has focused on the impact of individual communicative impairments on talk-in-interaction.

This special issue adds to a growing body of research which draws on the methods and findings of conversation analysis (CA) (Clift, 2016) to investigate the nature of conversation and other forms o...

The Addenbrooke’s Cognitive Examination (ACE-111) is a neuropsychological test used in clinical practice to inform a dementia diagnosis. The ACE-111 relies on standardized administration so that patients’ scores can be interpreted by comparison with normative scores. The test is delivered and responded to in interaction between clinicians and patients, which places talk-in-interaction at the heart of its administration. In this article, conversation analysis (CA) is used to investigate how the ACE-111 is delivered in clinical practice. Based on analysis of 40 video/audio-recorded memory clinic consultations in which the ACE-111 was used, we have found that administrative standardization is rarely achieved in practice. There was evidence of both (a) interactional variation in the way the clinicians introduce the test and (b) interactional non-standardization during its implementation. We show that variation and interactional non-standardization have implications for patients’ understanding and how they might respond to particular questions.

Background Mucosal-associated invariant T (MAIT) cells represent a specialized lymphocyte population associated with chronic inflammatory disorders. Little is known, however, about MAIT cells in diseases of the kidney, including CKD. Methods To evaluate MAIT cells in human native kidneys with tubulointerstitial fibrosis, the hallmark of CKD, we used multicolor flow cytometry to identify, enumerate, and phenotype such cells from human kidney tissue biopsy samples, and immunofluorescence microscopy to localize these cells. We cocultured MAIT cells and human primary proximal tubular epithelial cells (PTECs) under hypoxic (1% oxygen) conditions to enable examination of mechanistic tubulointerstitial interactions. Results We identified MAIT cells (CD3+ TCR Va7.2+ CD161hi) in healthy and diseased kidney tissues, detecting expression of tissue-resident markers (CD103/CD69) on MAIT cells in both states. Tissue samples from kidneys with tubulointerstitial fibrosis had significantly elevated numbers of MAIT cells compared with either nonfibrotic samples from diseased kidneys or tissue samples from healthy kidneys. Furthermore, CD69 expression levels, also an established marker of lymphocyte activation, were significantly increased on MAIT cells from fibrotic tissue samples. Immunofluorescent analyses of fibrotic kidney tissue identified MAIT cells accumulating adjacent to PTECs. Notably, MAIT cells activated in the presence of human PTECs under hypoxic conditions (modeling the fibrotic microenvironment) displayed significantly upregulated expression of CD69 and cytotoxic molecules perforin and granzyme B; we also observed a corresponding significant increase in PTEC necrosis in these cocultures. Conclusions Our findings indicate that human tissue-resident MAIT cells in the kidney may contribute to the fibrotic process of CKD via complex interactions with PTECs.

Proximal tubular epithelial cells (PTEC) are central players in inflammatory kidney diseases. However, the complex signalling mechanism/s via which polarized PTEC mediate disease progression are poorly understood. Small extracellular vesicles (sEV), including exosomes, are recognized as fundamental components of cellular communication and signalling courtesy of their molecular cargo (lipids, microRNA, proteins). In this study, we examined the molecular content and function of sEV secreted from the apical versus basolateral surfaces of polarized human primary PTEC under inflammatory diseased conditions. PTEC were cultured under normal and inflammatory conditions on Transwell inserts to enable separate collection and isolation of apical/basolateral sEV. Significantly increased numbers of apical and basolateral sEV were secreted under inflammatory conditions compared with equivalent normal conditions. Multi‐omics analysis revealed distinct molecular profiles (lipids, microRNA, proteins) between inflammatory and normal conditions for both apical and basolateral sEV. Biological pathway analyses of significantly differentially expressed molecules associated apical inflammatory sEV with processes of cell survival and immunological disease, while basolateral inflammatory sEV were linked to pathways of immune cell trafficking and cell‐to‐cell signalling. In line with this mechanistic concept, functional assays demonstrated significantly increased production of chemokines (monocyte chemoattractant protein‐1, interleukin‐8) and immuno‐regulatory cytokine interleukin‐10 by peripheral blood mononuclear cells activated with basolateral sEV derived from inflammatory PTEC. We propose that the distinct molecular composition of sEV released from the apical versus basolateral membranes of human inflammatory PTEC may reflect specialized functional roles, with basolateral‐derived sEV pivotal in modulating tubulointerstitial inflammatory responses observed in many immune‐mediated kidney diseases. These findings provide a rationale to further evaluate these sEV‐mediated inflammatory pathways as targets for biomarker and therapeutic development.

Wilkinson, Rae and Rasmussen provide a thorough, state-of-the-art Introduction to the growing field of Atypical Interaction, that is, conversations and other types of social interaction where one of the participants has a communicative impairment or communication disorder. These can include, for example, autism, dementia, learning disability, stammering or hearing impairment. The authors discuss how within this field the method of conversation analysis is used to record, transcribe and analyse these types of social interaction. They describe similarities and differences in the way that the different forms of communicative impairment can impact on social interaction, and they summarise the contribution that work in this areas has made to both communication disorder research and conversation analysis research on the nature of talk and social interaction.

Semantic dementia causes progressive communication difficulties that significantly impact on the person and their family. There is a paucity of research examining conversation skills in this condition and associated interventions to support interaction, such as life-story work. This study used a multiple case study design to: (a) explore the everyday conversation experiences of five individuals with semantic dementia and their spouses; and (b) examine how intervention using interaction-focused life-story work could support communication needs. A total of 74 home visits were conducted over a longitudinal period. An innovative combination of conversation analysis of video and audio data alongside biographical interviewing was used. Information derived from these strands was utilised to design an individually tailored life-story intervention. Cross-case analysis examined the contribution of life-story work to interaction and other aspects of care. Results showed that a range of challenges and skills were present within conversation. Life-story work was delivered in all cases using a variety of formats and the work could be conceptualised under various points of connection: interactional, emotional, new, practical and future. Detailed assessment was important to define aims for intervention and appropriate format(s) for life-story work for the individual concerned. Outcomes for communication in this study were not solely about supporting the telling of facts about the person's life but represented a broader focus to facilitate embodied and emotional connections. This study demonstrates that creativity within life-story work is important to foster social interaction, beyond information exchange, using both verbal and non-verbal behaviours. In addition, video data show promise for exploring in-the-moment outcomes for research and practice, particularly to capture the non-verbal dimensions of this work.

Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3 - CD56 + ) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 dim NK cell subset and particularly the CD56 bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 bright NK cells (NKp46 + CD117 + ) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ–producing CD56 bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease.

Background: There has been increasing interest in dementia care in recent years, including how practitioners, service providers and society in general can help individuals to live well with the condition. An important aspect to this is provision of advice to ensure conversation partners effectively support the person with dementia in conversation. Aims: To provide a descriptive review of the literature examining everyday conversation in dementia in order to inform practice and research. Methods & Procedures: This review used a method specifically developed for reviewing conversation analytic and related literature. A range of databases were searched using key words and explicitly described inclusion criteria leading to a final corpus of 50 titles. Using this qualitative methodology, each paper was examined and data extracted. The contribution of each of these is described and the implications for practice and research are outlined. Main Contribution: This review examined studies into conversation in Alzheimer's disease, vascular dementia and Lewy body dementia, grouping these into: early influential studies; work drawing on positioning theory; studies using social and linguistic approaches; collaborative storytelling; formulaic language; studies specifically using conversation analysis; and conversation as a target for individualized therapy. In addition, more recent work examining primary progressive aphasia and behavioural variant frontotemporal dementia was explored. Overall, this review indicates that research examining conversation in natural settings provides a rich source of data to explore not just the challenges within conversation for those taking part, but also the skills retained by the person with dementia. An important aspect of this understanding is the notion that these skills relate not only to information exchange but also aspects of social interaction. The role of others in scaffolding the conversation abilities of the person with dementia and the potential of this for developing interventions are discussed. Conclusions & Implications: The review indicates that interventions targeting conversation in dementia are often advocated in the literature but currently such approaches remain to be systematically evaluated. In addition, many of the important insights arising from these studies have yet to inform multidisciplinary dementia care practice.

Inflammatory immune cells play direct pathological roles in cases of acute kidney injury (AKI) and chronic kidney disease (CKD). However, the identification and characterization of distinct populations of leukocytes in human kidney biopsies have been confounded by the limitations of immunohistochemical (IHC)-based techniques used to detect them. This methodology is not amenable to the combinations of multiple markers necessary to unequivocally define discrete immune cell populations. We have developed a multi-parameter, flow cytometric-based approach that addresses the need for panels of cell-specific markers in the identification of immune cell populations, allowing both the accurate detection and quantitation of leukocyte subpopulations from a single, clinical kidney biopsy specimen. In this approach, fresh human kidney tissue is dissociated into a single cell suspension followed by antibody-labeling and flow cytometric-based acquisition and analysis. This novel technique provides a major step forward in identifying and enumerating immune cell subpopulations in human kidney disease and is a powerful platform to complement traditional histopathological examinations of clinical kidney biopsies.

Language, humans’ most distinctive trait, still remains a ‘mystery’ forevolutionary theory. It is underpinned by a universal infrastructure—cooperative turn-taking—which has been suggested as an ancient mechanismbridging the existing gap between the articulate human species and theirinarticulate primate cousins. However, we know remarkably little aboutturn-taking systems of non-human animals, and methodological confoundshave often prevented meaningful cross-species comparisons. Thus, theextent to which cooperative turn-taking is uniquely human or represents ahomologous and/or analogous trait is currently unknown. The presentpaper draws attention to this promising research avenue by providing an over-view of the state of the art of turn-taking in four animal taxa—birds, mammals,insects and anurans. It concludes with a new comparative framework to spurmore research into this research domain and to test which elements of thehuman turn-taking system are shared across species and taxa.

BACKGROUND: γδ T cells are effector lymphocytes recognized as key players during chronic inflammatory processes. Mouse studies suggest a pathological role for γδ T cells in models of kidney disease. Here we evaluated γδ T cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. METHODS: γδ T cells were extracted from human kidney tissue and enumerated and phenotyped by multicolour flow cytometry. Localization and cytokine production by γδ T cells was examined by immunofluorescent microscopy. RESULTS: We detected significantly elevated numbers of γδ T cells in diseased biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue. At a subset level, only numbers of Vδ1+ γδ T cells were significantly elevated in fibrotic kidney tissue. Expression levels of cluster of differentiation 161 (CD161), a marker of human memory T cells with potential for innate-like function and interleukin (IL)-17A production, were significantly elevated on γδ T cells from fibrotic biopsies compared with nonfibrotic kidney tissue. Flow cytometric characterization of CD161+ γδ T cells in fibrotic biopsies revealed significantly elevated expression of natural killer (NK) cell-associated markers CD56, CD16 and CD336 (NKp44) compared with CD161- γδ T cells, indicative of a cytotoxic phenotype. Immunofluorescent analysis of fibrotic kidney tissue localized the accumulation of γδ T cells within the tubulointerstitium, with γδ T cells identified, for the first time, as a source of pro-inflammatory cytokine IL-17A. CONCLUSIONS: Collectively, our data suggest that human effector γδ T cells contribute to the fibrotic process and thus progression to chronic kidney disease.

Human proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the disease process in a wide range of kidney diseases, yet their exosomal production and exosome molecular cargo remain a mystery. Here we investigate, for the first time, the production and molecular content of exosomes derived from primary human PTEC cultured under normal and diseased conditions representing a spectrum of in vivo disease severity from early inflammation, experienced in multiple initial kidney disease states, through to hypoxia, frequently seen in late stage chronic kidney disease (CKD) due to fibrosis and vascular compromise. We demonstrate a rapid reproducible methodology for the purification of PTEC-derived exosomes, identify increased numbers of exosomes from disease-state cultures and identify differential expression levels of both known and unique miRNA and protein species from exosomes derived from different disease-culture conditions. The validity of our approach is supported by the identification of miRNA, proteins and pathways with known CKD associations, providing a rationale to further evaluate these novel and known pathways as targets for therapeutic intervention.

Background Features of dysarthria associated with Parkinson's disease (PD), such as low volume, variable rate of speech and increased pauses, impact speaker intelligibility. Those affected report restricted interactional participation, although this area is under explored. Aims To examine naturally occurring instances of problems with intelligibility that resulted in multiple attempts at repair in order to consider repair initiation strategies that might restrict or enhance participation. Methods & Procedures Thirteen people with PD (PwPD) video-recorded over 10 h of informal conversation data in their home setting involving familiar conversation partners (CPs). Using a conversation analytic (CA) approach, and drawing on an existing typology of repair initiators (RIs) for everyday talk-in-interaction and their relative power to locate a turn's repairable element, the design and ordering of RIs used by CPs was addressed, alongside their local consequences. Outcomes & Results CPs tended to increase the specificity of their RIs in line with the existing typology, progressing from open class forms (e.g. ‘mm?’) to more specific forms (e.g. questions/partial repeats). Repeated open class repair initiators (OCRIs) were used where PD speakers’ self-repair attempts provided limited information. Sometimes, however, specificity was increased too soon, before enough syntactic knowledge was gleaned, which resulted in an extended repair sequence. Where one OCRI followed another, the second always took a different form: lexically or in terms of prosodic/non-verbal features. RI forms not described in the existing typology were also identified, such as ‘prompts to modify speech’ (e.g. ‘Speak louder’) and repeating/rephrasing the original first pair part (e.g. question), and their effectiveness examined. Conclusions & Implications First steps are presented towards the design of a communication intervention promoting the efficient resolution of repair to moderate social withdrawal and increase participation for this client group. Future research will need to explore the feasibility and acceptability of such a resource.

Background Descriptions of inflammatory cells infiltrating the human kidney rarely mention B cells, other than in the specific scenario of transplantation. In these reports, B cells are localized almost exclusively within the kidney tubulointerstitium where they are ideally placed to interact with proximal tubule epithelial cells (PTEC). We have previously shown that activated PTEC down-modulate autologous T lymphocyte and dendritic cell function. In this report, we extend these prior studies to describe PTEC-B cell interactions. Methods Stimulated B cells were cultured in the absence or presence of activated autologous human PTEC and monitored for proliferation, surface antigen expression, cytokine secretion and antibody (Ab) production. Results PTEC decreased B cell proliferative responses, whilst B cells cultured in the presence of PTEC displayed decreased levels of CD27, a marker of plasma B cells and memory cells. Interestingly, autologous PTEC also significantly decreased the number of B cells secreting both IgG and IgM and overall levels of Ab production. Transwell studies demonstrated that this modulation was primarily contact-dependent, and blocking studies with anti-PD-L1 led to partial restoration in Ab production. Further blocking studies targeting soluble HLA-G (sHLA-G) and IDO, two other immunoinhibitory molecules also up-regulated in our activated PTEC, demonstrated minor restoration of Ab responses. Discussion We report, for the first time, that PTEC are also able to modulate autologous B-cell phenotype and function via complex contact-dependent (PD-L1), soluble (sHLA-G) and intracellular (IDO) factors. We hypothesize that such mechanisms may have evolved to maintain peripheral immune-homeostasis, especially within the inflammatory milieu that exists within many kidney diseases.

The papers in this special issue share two major features in common. First, in each case, the research presented takes as its main focus of attention conversational interactions involving one or mo...

Background: In this single case study we draw on conversation analytic methods and findings to investigate how a speaker with aphasia produces mentions of persons within conversation and how these mentions are regularly treated by the speaker’s recipient as difficult to understand. As well as names, mentioning persons can involve other types of linguistic forms including category terms (such as “father”, “baby”, and “scanner girl” which are used in this data set) and pronouns. Mentioning can also involve different forms of action in relation to the mentioned person (e.g., referring to someone versus describing someone). Recurrently in this data set the recipient uses other-initiation of repair to display problems in understanding which particular individual is being mentioned by the person with aphasia (PWA) and what action is being signified in relation to that person.Aims: To investigate in what ways the PWA’s mentioning of persons in conversation leads to displays of problematic understanding for the r...

Background: Semantic dementia is a rarer dementia, classified as a type of frontotemporal dementia and a variant of primary progressive aphasia. Studies examining conversation in this condition and interventions to enhance participation in family life present as gaps in the research literature.\ud \ud Methods: Working with one family on a longitudinal basis, this study used conversation analysis and narrative analysis to provide a detailed assessment of communication . This information was used to design an individually tailored life story intervention to facilitate family interaction: a co-produced life story music DVD.\ud \ud Results: This intervention offered the family a resource that allowed the person with semantic dementia to display areas of retained competence and enhanced participation in interaction in a way that was not typically present in everyday conversation.\ud \ud Conclusions: It is argued that fostering greater opportunities for such in-the-moment connections is an important goal for intervention, particularly when language may be significantly compromised.

In this review, I discuss conversation analytic informed intervention for aphasia, a language disorder acquired following brain damage. As well as describing this form of intervention and outlining features of the studies produced over the last 15 to 20 years that provide evidence of its effectiveness, I discuss some features of this approach that may be of relevance to interventionist conversation analysis more generally. Data are in British English and in Swedish with English translation.

Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141hiand CD1c+myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141hiDCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c+DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141hiand CD1c+blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A+and CD1c+cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.

This paper discusses a child's participation in multi-party family interaction. Drawing from video-recordings of a family Christmas event, we examine instances where a child produces an initiating action that is unsuccessful at first in gaining the recipiency of the addressee(s). We show how for the child a regular issue might be not simply pursuing a response, but more generally mobilising the adult addressee's recipiency and engagement. The analysis describes the methods by which the child attempts to mobilise recipiency, how these attempts are responded to by the adults in the interaction, and how the child pursues recipiency when it is not gained in the first instance. Drawing on these empirical findings we examine the notion of children's ‘rights to speak’ in interaction, in particular reconceptualising it the along the lines of ‘rights to engage’. The paper contributes to understandings about children's communicative competence, as well as identifying more generic aspects of the management of multi-party interaction.

This paper uses conversation analysis to investigate the form and use of iconic gestures by a man with severe Broca-type aphasia in interaction with his speech and language therapist. Deconstructing iconic gestures into the different types of methods used to produce them, the paper analyzes how these gestures can depict certain entities, such as actions or types of people, in ways that may be understandable to the recipient. It is also observed that these iconic gestures can constitute gestural contributions, which not only communicate certain semantic meanings, but also accomplish social actions, such as answering or repairing. The implications of this analysis for our understanding of compensatory behavior in aphasia, and of augmentative and alternative communication in social interaction more generally, are discussed.

Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3

Background There has been increasing interest in dementia care in recent years, including how practitioners, service providers and society in general can help individuals to live well with the condition. An important aspect to this is provision of advice to ensure conversation partners effectively support the person with dementia in conversation. Aims To provide a descriptive review of the literature examining everyday conversation in dementia in order to inform practice and research. Methods & Procedures This review used a method specifically developed for reviewing conversation analytic and related literature. A range of databases were searched using key words and explicitly described inclusion criteria leading to a final corpus of 50 titles. Using this qualitative methodology, each paper was examined and data extracted. The contribution of each of these is described and the implications for practice and research are outlined. Main Contribution This review examined studies into conversation in Alzheimer's disease, vascular dementia and Lewy body dementia, grouping these into: early influential studies; work drawing on positioning theory; studies using social and linguistic approaches; collaborative storytelling; formulaic language; studies specifically using conversation analysis; and conversation as a target for individualized therapy. In addition, more recent work examining primary progressive aphasia and behavioural variant frontotemporal dementia was explored. Overall, this review indicates that research examining conversation in natural settings provides a rich source of data to explore not just the challenges within conversation for those taking part, but also the skills retained by the person with dementia. An important aspect of this understanding is the notion that these skills relate not only to information exchange but also aspects of social interaction. The role of others in scaffolding the conversation abilities of the person with dementia and the potential of this for developing interventions are discussed. Conclusions & Implications The review indicates that interventions targeting conversation in dementia are often advocated in the literature but currently such approaches remain to be systematically evaluated. In addition, many of the important insights arising from these studies have yet to inform multidisciplinary dementia care practice.