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BackgroundThe number of clinical studies evaluating the benefit of cytokine-induced killer cell (CIK) therapy, an adoptive immunotherapy, for colorectal cancer (CRC) are increasing. In many of these trials CIK therapy was co-administered with conventional cancer therapy. The aim of this review is to systematically assess the available literature, in which the majority were only in Chinese, on CIK therapy for the management of CRC using meta-analysis, and to identify parameters associated with successful CIK therapy implementation.MethodsProspective and retrospective clinical studies which compared CIK therapy to non-CIK therapy in CRC patients were searched for electronically on MEDLINE, Embase, CNKI and Wanfang Data databases. The clinical endpoints of overall survival (OS), progression-free survival (PFS), OS and PFS rates, overall response rate (ORR) and toxicity were meta-analysed using hazard (HR) and relative ratios (RR), and subgroup analyses were performed using Chi-square (Chi2) test and I-square (I2) statistics for study design, disease stage, co-therapy type, and timing of administration.ResultsIn total, 70 studies involving 6,743 patients were analysed. CIK therapy was favoured over non-CIK therapy for OS (HR=0.59, 95% CI: 0.53-0.65), PFS (HR=0.55, 95% CI: 0.47-0.63), and ORR (RR=0.65, 95% CI: 0.57-0.74) without increasing toxicity (HR=0.59, 95% CI 0.16-2.25). Subgroup analyses on OS and PFS by study design (randomised versus non-randomised study design), disease stage (Stage I-III versus Stage IV), co-treatment with dendritic cells (CIK versus DC-CIK therapy), or timing of therapy administration (concurrent versus sequential with co-administered anti-cancer therapy) also showed that the clinical benefit of CIK therapy was robust in any subgroup analysis. Furthermore, co-treatment with dendritic cells did not improve clinical outcomes over CIK therapy alone.ConclusionsCompared with standard therapy, patients who received additional CIK cell therapy had favourable outcomes without increased toxicity, warranting further investigation into CIK therapy for the treatment of CRC.Key MessageWhat is already known on this topicCytokine-induced killer cell (CIK) therapy is an adoptive immunotherapy used to treat both solid and haematological cancers for over 20 years. It is predominantly used in China, with multiple studies reporting benefit in colorectal cancer (CRC) patients. Despite this, CIK therapy treatment regimens are not widely used, possibly due in part to the majority of the literature about CIK therapy in CRC being reported in Chinese. Further, CIK therapy is commonly combined with other therapies but it is currently not known if there is a specific combination or treatment regimen that is optimal for CRC.What this study addsWe report the most comprehensive systematic review to date of CIK therapy for CRC patients, combining both Chinese and English language reports. Patients with CRC who received additional CIK therapy had better survival outcomes than with standard therapy alone. We also showed that the addition of dendritic cells (DC) to CIK therapy, common for CRC treatment, did not provide any clinical benefit over CIK therapy alone, and that CIK therapy is effective whether given concurrently or sequentially to standard treatment regimens.How this study might affect research, practice, or policyOur systematic review of Chinese and English publications shows that CRC patients benefit from the addition of CIK therapy to standard treatment protocols and warrants further international studies.

This study explores a particular kind of enactment in storytelling sequences where a story recipient is recruited by the teller as a designated character in the scene being acted out. Using the conversation-analytic methodological approach, we found that the enactment under investigation often occurred where a response (from the recruited recipient or another recipient) to some matters in the on-going telling was treated as misaligned or inapposite. We then show that the recipient may be recruited either implicitly or explicitly by (not) receiving specific instructions from the teller as to who or what to be enacted. We also show that the one being recruited was able to manage, during his/her enacted participation, the dual roles as a recipient of and a character in the story through multimodal resources. We argue that such enactments are one of the distinctive ways in which personal experiences are transformed and shared in mundane everyday life. Data are in Mandarin and Cantonese.

ObjectiveTo understand the dynamics of conversations between neonatologists and parents concerning limitation of life-sustaining treatments.DesignFormal conversations were recorded, transcribed and analysed according to the conventions and methods of conversation analysis.SettingTwo tertiary neonatal intensive care units.ParticipantsConsultant neonatal specialists and families.Main outcome measuresWe used conversation analysis and developed an inductive coding scheme for conversations based on the introduction of limiting life-sustaining treatments and on the parental responses.ResultsFrom recordings with 51 families, we identified 27 conversations about limiting life support with 20 families and 14 doctors. Neonatologists adopted three broad strategies: (1) ‘recommendations’, in which one course of action is presented and explicitly endorsed as the best course of action, (2) a ‘single-option choice’ format (conditional: referring to a choice that should be made, but without specifying or listing options), and (3) options (where the doctor explicitly refers to or lists options). Our conversation analysis-informed coding scheme was based on the opportunities available for parents to ask questions and assert their preference with minimal interactional constraint or pressure for a certain type of response. Response scores for parents presented with conditional formats (n=15, median 5.0) and options (n=10, median 5.0) were significantly higher than for those parents presented with ‘recommendations’ (n=16, median 3.75; p=0.002) and parents were more likely to express preferences (p=0.005).ConclusionEncouraging different approaches to conversations about limitation of life-supporting treatment may lead to better parent engagement and less misalignment between the conversational partners.

This article reports findings from a study of police interviews of people suspected of having committed relatively minor criminal offences, in a police station in England. The data comprise audio-recorded investigative interviews which were analysed using conversation analysis. It is focused on a communicative practice employed by police officers while questioning suspects. This practice is to ‘formulate’ what the suspect has just said; formulations are a means of summarising the suspect’s evidence in a particular phase of questioning, in such a way as to represent the suspect’s own words. Formulations, as a practice in talk-in-interaction, enable police officers to a) summarise the upshot of what a suspect has said during a period or phase of questioning, b) attribute this summary directly to a suspect’s ‘own words’, c) construct a suspect’s account (confirmation) as legally relevant, and which can d) elicit from the suspect a form of admission. Formulations are employed as a mechanism to rework prior descriptions and utterances by transforming and elaborating them and consolidating their legal relevance. Through this practice, police officers manage to attribute legal labels to what suspects have said during the interview, to their evidence (e.g. as denying, admitting, telling, etc.) as well as to the character of the incidents or events in question (e.g. assault, breach of harassment warning, criminal damage, arson). Formulating, therefore, is an interactional practice through which key legal work is accomplished in police interviews with suspects in England. It is a device that constitutes the fabric of law-in-action.

We report the development and assessment of a novel coding framework in the context of research into neonatal end-of-life decision making conversations. Data comprised 27 formal conversations between doctors and parents of critically ill babies, recorded in two neonatal intensive care units. The coding framework was developed from a qualitative analysis of the recordings using the method of conversation analysis (CA). Codes underpinned by our qualitative analysis had in the main moderate to strong agreement (inter-rater reliability) between coders; three codes had lower agreement reflecting the use of euphemisms for death and disability. Coding these interactions confirmed the significance of the doctors' talk in terms of parental involvement in decision-making, whilst highlighting areas warranting further qualitative analysis. This quantifiable representation provides a novel outcome based on evidence that is internal to the conversation rather than influenced by other factors related to the baby's care or outcome.

Alcohol use disorder (AUD) is one of the most common preventable mental health disorders and can result in pathology within the CNS, including the cerebellum. Cerebellar alcohol exposure during adulthood has been associated with disruptions in proper cerebellar function. However, the mechanisms regulating ethanol-induced cerebellar neuropathology are not well understood. High-throughput next generation sequencing was performed to compare control versus ethanol-treated adult C57BL/6J mice in a chronic plus binge model of AUD. Mice were euthanized, cerebella were microdissected, and RNA was isolated and submitted for RNA-sequencing. Down-stream transcriptomic analyses revealed significant changes in gene expression and global biological pathways in control versus ethanol-treated mice that included pathogen-influenced signaling pathways and cellular immune response pathways. Microglial-associated genes showed a decrease in homeostasis-associated transcripts and an increase in transcripts associated with chronic neurodegenerative diseases, while astrocyte-associated genes showed an increase in transcripts associated with acute injury. Oligodendrocyte lineage cell genes showed a decrease in transcripts associated with both immature progenitors as well as myelinating oligodendrocytes. These data provide new insight into the mechanisms by which ethanol induces cerebellar neuropathology and alterations to the immune response in AUD.

International audience; We have conducted conversational analysis of intrahospital telephone calls in which a recovery room nurse notifies the wards that, having concluded their treatment, a patient is ready for transfer. The article contributes to the understanding of recruitment as the outcome of interactional methods securing involvement-assistance, cooperation or contribution-in the realisation of courses of action. It shows that: a) informings conveyed by brief factual declaratives can act as a recruitment method even in the absence of any reference to a need, want or trouble; b) informing others of a state of affairs can act as a prompt for them to take responsive action under their own responsibility; c) informings as recruitment can be part of an organisational routine and instrumental in bringing forth remote professional action. Contrary to the common assumption that indirect forms of recruitment are normatively less constraining, we suggest that factual informings are actually an effective way of prompting a co-worker to act on their responsibilities. The data are audio-recordings of telephone calls made in an acute-care hospital in the French-speaking part of Switzerland.

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.

This is an investigation into conflict and discord in conversations between couples (heterosexual partners) in ordinary households in mainland China. Based on a corpus of face-to-face and telephone...

Goffman (1971) proposed that apologies are, or at least should be, proportional to the offenses they are designed to remediate. In a previous quantitative study (Heritage & Raymond 2016), we found mixed support for such a principle of proportionality. The present article aims to unpack some of the difficulties encountered in that largely positivistic analysis, by adopting a constitutive approach to the design, deployment, and negotiation of apologies in sequences of interaction. We begin by examining cases of self-correction, in which participants can be seen to be orienting to the (in)appositeness of apology formulations to deal with particular offenses. We then offer an in-depth comparison of two cases involving what is ostensibly the ‘same’ virtual offense, but in which the stance of the apologizer in each is quite different. After discussing three possible approaches to the divergence between these two cases, we conclude by arguing that the principle of proportionality is best conceived of as a normative structure to which participants orient even in the context of departing from it, thereby providing for its maintenance. Data come from everyday conversation amongst American and British speakers of English.

BACKGROUND: Black Americans and women report feeling doubted or dismissed by health professionals. OBJECTIVE: To identify linguistic mechanisms by which physicians communicate disbelief of patients in medical records and then to explore racial and gender differences in the use of such language. DESIGN: Cross-sectional. SETTING/PARTICIPANTS: All notes for patients seen in an academic ambulatory internal medicine practice in 2017. MAIN MEASURES: A content analysis of 600 clinic notes revealed three linguistic features suggesting disbelief: (1) quotes (e.g., had a “reaction” to the medication); (2) specific “judgment words” that suggest doubt (e.g., “claims” or “insists”); and (3) evidentials, a sentence construction in which patients’ symptoms or experience is reported as hearsay. We used natural language processing to evaluate the prevalence of these features in the remaining notes and tested differences by race and gender, using mixed-effects regression to account for clustering of notes within patients and providers. KEY RESULTS: Our sample included 9251 notes written by 165 physicians about 3374 unique patients. Most patients were identified as Black (74%) and female (58%). Notes written about Black patients had higher odds of containing at least one quote (OR 1.48, 95% CI 1.20–1.83) and at least one judgment word (OR 1.25, 95% CI 1.02–1.53), and used more evidentials (β 0.32, 95% CI 0.17–0.47), compared to notes of White patients. Notes about female vs. male patients did not differ in terms of judgment words or evidentials but had a higher odds of containing at least one quote (OR 1.22, 95% CI 1.05–1.44). CONCLUSIONS: Black patients may be subject to systematic bias in physicians’ perceptions of their credibility, a form of testimonial injustice. This is another potential mechanism for racial disparities in healthcare quality that should be further investigated and addressed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06682-z.

During daily hospital ward rounds, medical teams, led by doctors, assess the progress of an individual patient's health. It is widely reported in the research literature that nurses play a relatively passive role during these rounds, because although they may have valuable information about the patient's condition and progress, and indeed their role includes advocacy on behalf of their patients, nurses nevertheless can experience difficulties in participating during case constructions. Here we report an instance from a (gastro-surgical) ward round in a Finnish hospital, in which nurses played a key role in reversing a consultant's initial decision to discharge a patient. They did so not by directly challenging the consultant's opinion, but by employing indirect means to introduce their discrepant perspective: they provide descriptions and ask questions that draw attention to information that results in the doctor coming to a different assessment than theirs of the patient's condition, and a different decision about what should be done (the patient was not discharged from hospital). The encounter reported here is taken from a corpus of ward round discussions in a Finnish hospital. The method of our study is Conversation Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Perhexiline, a prophylactic anti-anginal drug, has been reported to have anti-tumour effects both in vitro and in vivo. Perhexiline as used clinically is a 50:50 racemic mixture ((R)-P) of (−) and (+) enantiomers. It is not known if the enantiomers differ in terms of their effects on cancer. In this study, we examined the cytotoxic capacity of perhexiline and its enantiomers ((−)-P and (+)-P) on CRC cell lines, grown as monolayers or spheroids, and patient-derived organoids. Treatment of CRC cell lines with (R)-P, (−)-P or (+)-P reduced cell viability, with IC50 values of ~4 µM. Treatment was associated with an increase in annexin V staining and caspase 3/7 activation, indicating apoptosis induction. Caspase 3/7 activation and loss of structural integrity were also observed in CRC cell lines grown as spheroids. Drug treatment at clinically relevant concentrations significantly reduced the viability of patient-derived CRC organoids. Given these in vitro findings, perhexiline, as a racemic mixture or its enantiomers, warrants further investigation as a repurposed drug for use in the management of CRC.

I explore some of the interconnections between inferences that participants make about one another’s (verbal) conduct, the implications they attribute to prior turns at talk, and the indirectness with which recipients may respond to enquiries - in short, the interconnections between inference, implication and indirectness. These are explored in the context of naturally occurring conversations (UK and US), from the methodological perspective of Conversation Analysis. Because inference has come to be associated closely with Grice’s concept of implicature, I begin by setting out my reasons for not following Grice’s path, preferring instead to revert to ‘implication’, namely the implication that a recipient finds in and attributes to a prior turn. My purpose here is to avoid the cognitive conceptualisation of speakers’ intentions that Grice supposed are associated with implicature. I argue that inference features in the understanding of and response to all turns at talk; it is not restricted to some special kind of utterance, as seems to be conveyed in Grice’s conceptualisation. The inferences that recipients make are evident in cases in which they respond not to what the prior speaker asked ‘literally,’ but to the inferred agenda of an enquiry. Moreover, recipients may respond indirectly to prior enquiries, thereby ‘side-stepping’ implications they attribute to those enquiries. In various ways, inference and indirection may on occasions be associated with practices for avoidance in conversation.

A Special Issue of this journal, edited by Lynch et al., was published critiquing research in conversation analysis (CA) on epistemics and on oh. It would be more accurate to say that the articles in that Special Issue critique the work of Heritage on epistemics and oh. Their principal criticism is that Heritage’s analyses of epistemics and oh are cognitivist. Other criticisms are that his analysis of each of these phenomena is not sequential, that it does not attend to the details of turn design, and that his analyses are not truly conversation analytic – indeed that he does not comprehend CA, that his analyses are false and unwarranted, that he has adopted an ‘informationist’ perspective of knowledge transfer, and that epistemics represents some ‘hidden order’ invisible at the surface of conversation. Underlying these criticisms is their contention that Heritage has not adhered to the ‘radical’ agenda of ethnomethodology (or the agenda of ‘radical ethnomethodology’) which, they claim, underlies the origins of CA. In this Introduction, I outline some of the principal reasons for regarding the criticisms in The epistemics of Epistemics to be misguided, inaccurate and scurrilous. In doing so, I am setting out in very broad outline the arguments made by the contributors to this Special Issue rebutting those criticisms of Heritage’s work, and of CA more generally.

My argument here is principally that the ubiquity of (the relevance of) epistemics is evident in the ways in which knowledge claims and attributions of knowledge to self and other (1) are embedded in turns and sequences, (2) inform the design of turns at talk, (3) are amended in the corrections that speakers sometimes make, to change from one epistemic stance to another (e.g. from K+ to K−), and (4) are contested, in the occasional ‘struggles’ between participants, as to which of them has epistemic primacy. I show that these cannot be understood in cognitive terms; furthermore, I show that epistemics – again the attribution of knowledge to self and other – is ‘real’ for participants. That is, in these four practices and aspects of interaction (i.e. embedding, turn design, correction and contesting) it is evident that participants orient to their states of knowledge relative to one another, on a moment-by-moment, turn-by-turn basis.

Examining a corpus of invitations made in telephone calls, in English (US and UK), there is evidently some variation in the design of turns in which the invitations are made, in their lexico-grammatical format. The variations in the forms through which these invitations are delivered are associated, broadly speaking, with two intersecting contingencies; the sequential and interactional circumstances (environment) in which the invitation is being made, and the kind of occasion that is represented in the invitation. The ways in which the design form(at) of an invitation is shaped by its interactional environment and represents a particular ‘kind of occasion’ is explored here. However, there is something further which, across the variations in their specific lexico-grammatical design, these designs tend to have in common – that is, that they are variations of equivocal forms of invitation (in contrast to grammatically ‘assertive’ forms); that is there is an uncertainty, a tentativeness in asking, amounting to a kind of cautiousness. This paper reports these equivocal forms through which invitations are most commonly made.

This special issue of the Journal of Pragmatics concerns the activity of inviting and responding to invitations in authentic telephone calls in six different languages. Using Conversational Analysis to investigate telephone calls that were audio- recorded in family homes, and in one case, in a bank office, the papers focus on invitations to friends, famiily members, acquaintances and other casual recipients in ordinary and institutional conversations.