320 research outputs found
Management of diarrhea in patients with HER2-positive breast cancer treated with neratinib: A case series and summary of the literature
INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021.
CASE SERIES: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder.
MANAGEMENT AND OUTCOME: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy.
DISCUSSION: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib
The acquisition of Sign Language: The impact of phonetic complexity on phonology
Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality
Phonological Coding during Sentence Reading in Chinese Deaf Readers: An Eye-Tracking Study
Phonological coding plays an important role in reading for hearing students. 3 Experimental findings regarding phonological coding in deaf readers are 4 controversial, and whether deaf readers are able to use phonological coding 5 remains unclear. In the current study we examined whether Chinese deaf students 6 could use phonological coding during sentence reading. Deaf middle school 7 students, chronological age-matched hearing students, and reading ability-8 matched hearing students had their eye movements recorded as they read 9 sentences containing correctly spelled characters, homophones, or unrelated 10 characters. Both hearing groups had shorter total reading times on homophones 11 than they did on unrelated characters. In contrast, no significant difference was 12 found between homophones and unrelated characters for the deaf students. 13 However, when the deaf group was divided into more-skilled and less-skilled 14 readers according to their scores on reading fluency, the homophone advantage 15 noted for the hearing controls was also observed for the more-skilled deaf 16 students
Resolving a gender and language problem in women’s leadership:consultancy research in workplace discourse
This article considers the contribution that consultancy research might make to resolving communication problems that women have identified in their leadership practices. Within the intersecting fields of gender and language and workplace discourse, consultancy research-that is, practitioner-commissioned research to resolve work-related, communication problems-is still uncommon. This article presents a study of Monika, a senior leader in an engineering company, who commissioned me to find out why she was experiencing communication problems with her teams. By using interactional sociolinguistic analysis, I was able to show Monika how her authority was being resisted on gendered, linguistic grounds. In making the case for more consultancy research, I discuss how we might use insights from discourse analysis to offer guidance to practitioners seeking our help
The (In)Authenticity of Simulated Talk: Comparing Role-Played and Actual Interaction and the Implications for Communication Training
This article was published in the journal, Research on Language and Social Interaction [Taylor & Francis (Routledge)] and the definitive version is available at: http://dx.doi.org/10.1080/08351813.2013.780341How authentic is simulated, or role-played, interaction, of the kind produced in communication training contexts? The article addresses this question by comparing actual and role-played police investigative interviews. Both types of interviews were recorded by the police: real ones to fulfill British legal requirements and training ones to maximize the authenticity of the training experience. Interview openings were examined using conversation analysis. Officers must adhere to Police and Criminal Evidence Act (2008) guidelines, turning them into spoken actions. The analyses revealed that while, in gross terms, officers in real and simulated interviews opened interviews by formulating the same actions (e.g., identifying copresent parties), differences were observable in their design and organization. In simulations, actions were more elaborate or exaggerated; that is, they were made interactionally visible and “assessable.” Furthermore, some actions were only present in simulations. Implications for the efficacy of role-play methods for training and assessing communication are discussed
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Segmentation of British Sign Language (BSL): Mind the gap!
This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous signing, there are salient transitions between sign locations. We used the sign-spotting task to ask if and how BSL signers use these transitions in segmentation. A total of 96 real BSL signs were preceded by nonsense signs which were produced in either the target location or another location (with a small or large transition). Half of the transitions were within the same major body area (e.g., head) and half were across body areas (e.g., chest to hand). Deaf adult BSL users (a group of natives and early learners, and a group of late learners) spotted target signs best when there was a minimal transition and worst when there was a large transition. When location changes were present, both groups performed better when transitions were to a different body area than when they were within the same area. These findings suggest that transitions do not provide explicit sign-boundary cues in a modality-specific fashion. Instead, we argue that smaller transitions help recognition in a modality-general way by limiting lexical search to signs within location neighbourhoods, and that transitions across body areas also aid segmentation in a modality-general way, by providing a phonotactic cue to a sign boundary. We propose that sign segmentation is based on modality-general procedures which are core language-processing mechanisms
Intervening With Conversation Analysis in Telephone Helpline Services: Strategies to Improve Effectiveness
This is an Accepted Manuscript of an article published by Taylor & Francis Group in the Research on Language and Social Interaction on 06/08/2014, available online: http://dx.doi.org/10.1080/08351813.2014.925661This article overviews the way conversation analytic work on telephone helplines can make an impact in practical situations. It takes three illustrative themes in helpline research: (a) the giving, receiving, and resisting of advice; (b) the expression of strong emotion and its identification, management, and then coordination with helpline goals; and (c) how helplines' policies and practices shape the interactions between caller and call taker. For each of these themes, we show how conversation analysis research insights have been applied to improve helpline effectiveness. This has been done through a variety of practice-based reports, consultancy exercises, and training initiatives, including workshops where we aim to identify and facilitate good practice. Intervention studies of this type are at the forefront of interactional research on telephone helplines. Data are in Australian and British English
Atrial arrhythmogenesis in wild-type and Scn5a+/Δ murine hearts modelling LQT3 syndrome
Long QT(3) (LQT3) syndrome is associated with abnormal repolarisation kinetics, prolonged action potential durations (APD) and QT intervals and may lead to life-threatening ventricular arrhythmias. However, there have been few physiological studies of its effects on atrial electrophysiology. Programmed electrical stimulation and burst pacing induced atrial arrhythmic episodes in 16 out of 16 (16/16) wild-type (WT) and 7/16 genetically modified Scn5a+/Δ (KPQ) Langendorff-perfused murine hearts modelling LQT3 (P < 0.001 for both), and in 14/16 WT and 1/16 KPQ hearts (P < 0.001 for both; Fisher’s exact test), respectively. The arrhythmogenic WT hearts had significantly larger positive critical intervals (CI), given by the difference between atrial effective refractory periods (AERPs) and action potential durations at 90% recovery (APD90), compared to KPQ hearts (8.1 and 3.2 ms, respectively, P < 0.001). Flecainide prevented atrial arrhythmias in all arrhythmogenic WT (P < 0.001) and KPQ hearts (P < 0.05). It prolonged the AERP to a larger extent than it did the APD90 in both WT and KPQ groups, giving negative CIs. Quinidine similarly exerted anti-arrhythmic effects, prolonged AERP over corresponding APD90 in both WT and KPQ groups. These findings, thus, demonstrate, for the first time, inhibitory effects of the KPQ mutation on atrial arrhythmogenesis and its modification by flecainide and quinidine. They attribute these findings to differences in the CI between WT and mutant hearts, in the presence or absence of these drugs. Thus, prolongation of APD90 over AERP gave positive CI values and increased atrial arrhythmogenicity whereas lengthening of AERP over APD90 reduced such CI values and produced the opposite effect
Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis
In human type 1 diabetes (T1D) and in its murine model, the major histocompatibility complex (MHC) class II molecules, human leukocyte antigens (HLA)-DQ and -DR and their murine orthologues, IA and IE, are the major genetic determinants. In this report, we have ranked HLA class II molecule-associated T1D risk in a two-sided gradient from very high to very low. Very low risk corresponded to dominant protection from T1D. We predicted the protein structure of DQ by using the published crystal structures of different allotypes of the murine orthologue of DQ, IA. We discovered marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules showed conserved similarities that contrasted with the shared patterns observed between the protective molecules. We also found striking inter-isotypic conservation between protective DQ, IA allotypes and protective DR4 subtypes. The data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall, these results suggest shared epitope(s) in the target autoantigen(s), and common pathways in human and murine T1D
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