The working alliance in stuttering treatment: a neglected variable?

Background Multiple factors can influence the working alliance and treatment outcome in speech and language therapy. The ‘working alliance’ is an important concept in treatment and can be described as the degree to which a treatment dyad is engaged in collaborative, purposive work. To date, relatively little attention has been paid to this concept within speech and language treatment in general, and within stuttering treatment research in particular. Aims To investigate the role of the working alliance within stuttering treatment, and to evaluate whether the quality of the working alliance correlated with clients’ concept of motivation and treatment outcomes 6 months post‐therapy. Methods & Procedures Eighteen adults (21‐61 years) participated in this multiple single‐case treatment study, with treatment facilitated by an experienced speech and language therapist. The working alliance was investigated using the Working Alliance Inventory—Short Version Revised (WAI‐SR), an Extended version of the Client Preferences for Stuttering Treatment (CPST‐E), the Overall Assessment of Speakers’ Experience of Stuttering—Adult version (OASES‐A), the Wright & Ayre Stuttering Self‐Rating Profile (WASSP) and the Hospital Anxiety and Depression Scale (HADS). Outcomes & Results Analyses demonstrated significant associations between the working alliance and client motivation (r = 0.781) and treatment outcomes (r = 0.644) 6 months post‐treatment. The association between client‐led goals and therapy tasks appeared particularly important. Conclusions & Implications The working alliance between speech and language therapists and persons who stutter matters. Within the alliance, the level of client–clinician agreement on treatment goals and therapy tasks may be of greater importance than the bond between client and clinician. Further research with greater numbers of participants is warranted

Matured hiPSC-derived cardiomyocytes possess dematuration plasticity

Human induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used to identify potential factors capable of inducing endogenous cardiomyocyte proliferation to regenerate the injured heart. L-type calcium channel blockers have previously been identified as a class of factors capable of inducing matured hiPSC-CMs to proliferate. However, the mechanism by which L-type calcium channel blockers promote hiPSC-CM proliferation remains unclear. Here we provide evidence that matured hiPSC-CMs possess plasticity to undergo dematuration in response to certain pharmacological compounds. Consistent with primary cardiomyocyte maturation during perinatal development, we found that centrosome disassembly occurs in hiPSC-CMs during plate-based, temporal, maturation. A small molecule screen identified nitrendipine, an L-type calcium channel blocker, and 1-NA-PP1, a Src kinase inhibitor, as factors capable of inducing centrosome reassembly in a subpopulation of hiPSC-CMs. Furthermore, centrosome-positive hiPSC-CMs were more likely to exhibit cell cycle activity than centrosome-negative hiPSC-CMs. In contrast, neither nitrendipine or 1-NA-PP1 induced centrosome reassembly, or cell cycle activity, in neonatal rat ventricular myocytes (NRVMs). Differential bulk transcriptome analysis indicated that matured hiPSC-CMs, but not NRVMs, treated with nitrendipine or 1-NA-PP1 undergo dematuration. ScRNA transcriptome analysis supported that matured hiPSC-CMs treated with either nitrendipine or 1-NA-PP1 undergo dematuration. Collectively, our results indicate that matured hiPSC-CMs, but not primary NRVMs, possess plasticity to undergo dematuration in response to certain pharmacological compounds such as L-type calcium channel blockers and Src-kinase inhibitors. This study shows that once mature, hiPSC-CMs may not maintain their maturity under experimental conditions which may have implications for experimental systems where the state of hiPSC-CM maturation is relevant.</p

Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic

Resilience beyond neoliberalism? Mystique of complexity, financial crises, and the reproduction of neoliberal life

The burgeoning debate on resilience in international relations has seen the emergence of two polarized views: resilience as a manifestation of neoliberal governmentality and resilience as the expression of a post-neoliberal shift. This article explores whether a post-neoliberal resilience may be possible by reflecting upon the ontology of complexity as unknowability at the heart of this view. It argues that this approach neglects how the discourse of complexity as unknowability is a neoliberal technology of government that is instrumental to advance neoliberal forms of resilience. The second half of the article discusses this argument with reference to the 2008 financial crisis. It shows how a resilience-as-post-neoliberal approach resonates with those dominant narratives which have shrouded the causes and mechanics of the crisis in a mystique of complexity, thus encouraging forms of cognitive and political disengagement. The article concludes that by celebrating local knowledge at the expense of an understanding of global dynamics, post-neoliberal resilience offers an impoverished notion of resistance compliant with the dictates of the neoliberal order

Capturing protest in urban environments:The ‘police kettle’ as a territorial strategy

‘Kettling’ has emerged in recent decades as an established, if controversial, tactic of public order policing. Departing from a historical emphasis on dispersal, kettling instead acts to contain protesters within a police cordon for sustained periods of time. This article elaborates upon the spatial and temporal logics of kettling by investigating the conditions of is historical emergence. We argue that kettling should be understood as a territorial strategy that co-evolved in relation to forms of disruptive protest. Whereas techniques of crowd dispersal serve to diffuse a unified collective, ‘kettling’ aims to capture the volatile intensities of public dissent and exhaust its political energies. Drawing on police manuals, media coverage, accounts from activists and expert interviews, we show how the ‘kettle’ re-territorializes protest by acting on its spatio-temporal and affective constitution. By fabricating an inner outside of the urban milieu, freezing the time of collective mobilization and inducing debilitating affects such as fear and boredom, kettling intervenes into the scene of political subjectification that each congregation of protesting bodies seeks to fashion

Ascites induces modulation of α6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma

Interactions between cancer cells and the surrounding medium are not fully understood. In this study, we demonstrate that ascites induces selective changes in the expression of integrins and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) in ovarian cancer cells. We hypothesise that this change of integrin and uPA/uPAR expression triggers signalling pathways responsible for modulating phenotype-dependent functional changes in ovarian cancer cells. Human ovarian surface epithelial (HOSE) cell lines and epithelial ovarian cancer cell lines were treated with ascites for 48 h. Ascites induced upregulation of α6 integrin, without any change in the expression of αv, β1 and β4 integrin subunits. Out of the four ovarian cancer cell lines studied, ascites induced enhancement in the expression of uPA/uPAR in the more invasive OVCA 433 and HEY cell lines without any change in the noninvasive OVHS1 and moderately invasive PEO.36 cell lines. On the other hand, no change in the expression of α6 integrin or uPAR, in response to ascites, was observed in HOSE cells. In response to ascites, enhancement in proliferation and in adhesion was observed in all four ovarian cancer cell lines studied. In contrast, no significant increase in proliferation or adhesion by ascites was observed in HOSE cells. Ascites-induced expression of uPA/uPAR correlated with the increased invasiveness of HEY and OVCA 433 cell lines but was not seen in OVHS1, PEO.36 and HOSE cell lines. Upregulation of α6 integrin and uPA/uPAR correlated with the activation of Ras and downstream Erk pathways. Ascites-induced activation of Ras and downstream Erk can be inhibited by using inhibitory antibodies against α6 and β1 integrin and uPAR, consistent with the inhibition of proliferation, adhesion and invasive functions of ovarian cancer cell lines. Based on these findings, we conclude that ascites can induce selective upregulation of integrin and uPA/uPAR in ovarian cancer cells and these changes may modulate the functions of ovarian carcinomas

Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis

Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3±0.5 ml (mean±s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer