Optimisation of a chimeric antigen receptor targeting anaplastic lymphoma kinase for immunotherapy for childhood solid cancers

Cancer immunotherapy with chimeric antigen receptor (CAR) engineered T cells has shown great promise in the treatment of haematological malignancies. Paediatric neuroblastoma is one of the most common solid extracranial tumours found in children and currently accounts for ~15% of deaths from childhood cancers. Despite multimodal chemotherapy and immunotherapeutic strategies, high-risk patients suffer relapse and treatment related morbidities. This project aims to optimise a novel CAR, targeting the neuroblastoma associated antigen, anaplastic lymphoma kinase (ALK) and we hypothesised that ALK will represent a suitable target this therapy. A panel of second generation anti-ALK CAR T cells was investigated containing multiple anti-ALK single chain variable fragments (scFvs) and stalk regions combined with CD28 and CD3ζ signalling endodomains. In vitro investigations demonstrated effective functional activity at high target antigen densities, which significantly diminishes at lower antigen expression levels. ALK8-CD8-28ζ demonstrated antigen dependent and ALK restricted cytotoxic activity, cytokine production and proliferation and was therefore identified as the ‘lead’ CAR. Interestingly, when the same anti-ALK binder was combined with an Fc spacer of differing origin and length, there was an indication of antigen independent proliferation, indicative of tonic signalling. Despite this differing activity, there were minimal differences found between the ALK-CAR T cells’ activation, exhaustion and memory immunophenotypes. ALK8-CD8-28ζ was compared to another panel of ALK-CAR T cells combining a previously published anti-ALK scFv with various stalk and transmembrane regions, however ALK8-CD8-28ζ demonstrated superior activity in cytokine and proliferation assays. Finally, ALK was combined into a dual-targeting CAR T cell system with another neuroblastoma associated antigen, GD2, in an attempt to increase in vitro activity at low target antigen densities. Despite evidence of background single endodomain CAR activity, the engagement of the double targeting CAR T cell demonstrated increased levels of antigen specific proliferation, proinflammatory cytokine release, activation and degranulation

Testing a dissonance body image intervention among young girls

Objective: Body image and eating disorder interventions based on cognitive dissonance have been shown to be effective among girls and women aged 14 and above. This article reports a preliminary examination of whether a dissonance intervention is also effective when delivered in a school setting to 12- and 13-year-old girls in the United Kingdom Method: Girls (N =106, mean age =12.07 years, SD =.27) were allocated to the intervention condition or a waitlist control. Results: In contrast to the control group, girls in the intervention condition reported significant reductions in body dissatisfaction and internalization of a thin body ideal post-intervention. There was no significant change in self-reported dietary restraint for either condition. In addition, compared with the control group, girls in the intervention condition showed increased resilience to negative media effects 1-month post-intervention. Conclusions: Results suggests that dissonance based programs can reduce body dissatisfaction, internalization and negative media effects among a younger group of girls than previously examined and in an United Kingdom school setting. © 2013 American Psychological Association

Can appearance conversations explain differences between gay and heterosexual men's body dissatisfaction?

Men's body dissatisfaction is prevalent and a serious health concern as it is associated with negative outcomes including depression, disordered eating, and anabolic steroid abuse. Gay men are particularly vulnerable to body dissatisfaction, perhaps due to heightened sociocultural appearance pressures experienced in gay subculture. Appearance conversations represent an underresearched, but potentially potent, mechanism of appearance pressures. The current study explored whether differences in the frequency of engaging in appearance conversations accounted for differences in body dissatisfaction and associated risk factors among gay and heterosexual men. A purposeful sample of gay (N = 77, Mage = 32.57) and heterosexual (N = 78, Mage = 25.30) men were recruited from community organizations in the United Kingdom. Participants completed an online questionnaire assessing appearance conversations, body dissatisfaction, appearance orientation, and internalization of appearance ideals. Gay men reported more frequent engagement in positive and negative appearance conversations and greater body dissatisfaction, appearance orientation, and general internalization than heterosexual men. Moreover, frequency of appearance conversations mediated the relationship between sexuality and the majority of study variables, including body dissatisfaction (ps<.05). These findings suggest that appearance conversations are an important sociocultural influence on male body image and that they are important in understanding the differences between gay and heterosexual men's body dissatisfaction and associated risk factors. © 2013 American Psychological Association

An exploration of bisexual, lesbian, and heterosexual women's body dissatisfaction, and body hair and make-up practices

Body image pressures for heterosexual women are well established. However, lesbian body image is less well understood, while bisexual women have largely been overlooked with the psychological literature. Further, women's investment in ‘traditional’ appearance practices associated with femininity are underexplored. The current study explored differences between 472 heterosexual, lesbian, and bisexual women on measures of body satisfaction, body hair practices, and cosmetics use. While there were no significant differences between body satisfaction scores, lesbian and bisexual women had more positive attitudes to body hair, and were less likely to remove hair from particular parts of their bodies, than heterosexual women. Cosmetics use was highest among heterosexual women, significantly lower among bisexual women, and lowest among lesbians. We argue that these results highlight the importance of exploring the distinctiveness of bisexual, lesbian and heterosexual women's appearance concerns and appearance practices

Costing the invisible: A review of the evidence examining the links between body image, aspirations, education and workplace confidence

Throughout the world, girls and women are interested in their looks. What has been perceived as an enjoyable part of life is however imbued with negative economic and psychological costs which are rarely calculated. International studies confirm the disturbing trend that body dissatisfaction and the perception that one is too large (even if this is not the case) undermine adolescent girls’ academic achievement. It doesn’t lead to failure, but to a diminishing in confidence and hence in performance. The marketing of beauty aimed at girls as young as five through to women in their seventies has made the idea of beauty more accessible but simultaneously, the narrowing of the ideal standard to very young women with one body type, one look, one shape, one colour, one breast or buttock size whose images are then photo-shopped to create bodies that rarely exist in real life - and are frequently unrecognizable to the model herself - has had many unfortunate consequences. The beauty ideals which saturate all media from facebook, to tumblr, to instagram, to mainstream magazines, music videos and billboards, create anxiety and shame around personal appearance.Concern about looks, size, weight, shape and attractiveness filch girls’ and women’s minds, passions and bodies. There is an urgent need for multi-level intervention to reverse the trend of poor body image and poor body confidence. The silent self-attacks are thwarting girls’ ambitions at exactly the time when society is apparently opening up to them. Programmes and social policy that can interrupt the cycle of undermining that is intensifying need to be underpinned by robust research, which can demonstrate the economic and psychological case for underpinning girls’ capability and can demonstrate the effectiveness of such strategies. The substantial economic costs of clinical eating disorders and obesity have been assessed in terms of present and future expenditure to the NHS and opportunities lost for young women. However, no costing exists of the ubiquitous breeding of body insecurity which takes form in the growth of appearance anxiety, body dysmorphias, bulimic behaviours, compulsive eating, and confidence issues, many of which are now normative and widespread among adults and young people. It is urgently required

Adapting the Body Appreciation Scale-2 for Children: A psychometric analysis of the BAS-2C

© 2017 Positive body image among adults is related to numerous indicators of well-being. However, no research has explored body appreciation among children. To facilitate our understanding of children's positive body image, the current study adapts and validates the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a) for use with children. Three hundred and forty-four children (54.4% girls) aged 9–11 completed the adapted Body Appreciation Scale-2 for Children (BAS-2C) alongside measures of body esteem, media influence, body surveillance, mood, and dieting. A sub-sample of 154 participants (62.3% girls) completed the questionnaire 6-weeks later to examine stability (test-retest) reliability. The BAS-2C displayed a unidimensional factor structure and evidence of internal consistency, test-retest reliability, and construct, criterion-related, and incremental validity. Additionally, the results suggest adaptive properties of body appreciation for body-related and emotional well-being among children. The BAS-2C could serve as an essential component within research to understand and estimate children's positive body image

Evaluating the impact of a brief yoga intervention on preadolescents’ body image and mood

Yoga is an embodying activity that promotes body awareness, body connection, body responsiveness, and appreciation of body functionality, and it therefore may be a beneficial school-based intervention for children’s body image. The present study examined the impact of a 4-week yoga intervention on pre-adolescent girls’ and boys’ body image (body appreciation, body esteem, and body surveillance) and mood (positive and negative affect) 1-week post-intervention and at 6-week follow-up. British children (N = 344; 54.4% female) aged 9-11 years were recruited from four schools, two of which were randomly assigned to the yoga intervention and two to a physical education control condition. Unexpectedly, both groups increased body appreciation, body esteem, and positive mood, and decreased body surveillance and negative affect from baseline to post-intervention and/or follow-up. Children in the yoga intervention evaluated the sessions very favourably; the majority desired to participate in more lessons. Potential explanations for these findings are discussed

Quantifying the sources of variation in eosinophilia among Scottish blackface lambs with mixed, predominantly Teladorsagia circumcincta nematode infection

Eosinophils play a key role in defence against gastrointestinal nematodes. There is considerable variation among animals in the intensity of eosinophilia following nematode infection. However, the statistical distribution of eosinophils among animals has still to be determined. A better description of the variation among animals could provide biological insight and determine the most appropriate way to analyse the effect of eosinophils. We estimated blood eosinophil numbers in a flock of Scottish Blackface sheep that were naturally exposed to mixed, predominantly Teladorsagia circumcincta infection. Three of the four eosinophil counts were better described by a gamma distribution than by a lognormal distribution. The scale and shape parameters of the gamma distribution varied over time. Eosinophil counts differed among animals kept on separate fields before weaning and between singletons and twins but were not significantly different between years and genders. Eosinophil counts also differed among offspring from different sires and dams. The parameters of the gamma distribution were used to enable a power analysis. Large numbers of animals were required to reliably detect even large differences between two groups. These results indicate that methods appropriate for gamma distributions, such as generalized linear mixed models, will provide more reliable inferences than traditional methods of analysis and experimental design. © 2021 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “David Piedrafita and Sarah Preston” is provided in this record*

Exploring digital fiction as a tool for teenage body image bibliotherapy

This article reflects on the findings of the interdisciplinary ‘TransForm’ project, which ran between 2012 and 2014 and aimed to explore how reading and writing digital fictions (DFs) might support young women in developing frameworks for more positive thinking regarding their body image. The project comprised the following stages: (1) a review and compilation of DFs thematising and/or problematising female corporeality; (2) a series of cooperative inquiries with 3 groups of young women (aged 16–19 years) over a period of 5 weeks, examining participants’ responses to a selection of the previously compiled DFs, as well as the challenges these young women face in relation to body image and (3) an interventionist summer school in which participants aged 16–19 explored body image issues via writing DFs. This article reports on the main observations and findings of each stage, and draws conclusions for future research needs in this area