A study of peer activity in the early years through a range of contextual frameworks

This report focuses on exploring peer activity in the early years through a range of contextual frameworks. The research is conducted within a children's centre that provides nursery education for children aged 3-4 years as defined by the Early Years Foundation Stage - EYFS (2007). Research rationale focuses on the notion of, 'reflexive co-construction' through 'sustained shared thinking' (Siraj-Blatchford, 2002, p10). In order to appreciate this concept more fully among peers, it is suggested that a robust pedagogy is required to enhance the practitioner's understanding of peer activity. It is argued that context and peer activity are inextricably linked. If we are to consider peer activity, then its relationship with context must be more fully studied and articulated than in previous discussions. From a socio-constructivist standpoint, the study applies four different, but complementary theoretical perspectives to more fully describe and analyse the social realities children encounter on a daily basis. These perspectives are, an ecological understanding of human development, distributed cognition, activity theory and situated action. Peer literature in the early years is both varied and confusing in terms of context and outcome. Because of this predicament, it is suggested that there is an opening for studying peer activity from a contextual viewpoint. The research applies a qualitative ethnographic and observational approach. Data is generated from documentation, observations of, and discussions with, children and staff and is analysed within the four identified theoretical perspectives. The application of distributed cognition, activity theory and situated action further illuminates how children use a range of strategies to engage with one another. The research argues that such interactions within differing contexts create unique opportunities for reflexive co-construction amongst the children themselves. What emerges from this work is a pedagogical model, relating to peers and 'reflexive co-construction', which provides another dimension to current early years educational documentation

Some animals are more equal than others: Validation of a new scale to measure how attitudes to animals depend on species and human purpose of use

© 2020 Bradley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Globally, many millions of animals are used by humans every year and much of this usage causes public concern. A new scale, devised to measure attitudes to animal use in relation to the purpose of use and species, the Animal Purpose Questionnaire (APQ), was completed by in total 483 participants, 415 British nationals and 68 participants from 39 other countries. The APQ was presented in two survey formats, alongside an established Animal Attitudes Scale (AAS). In both surveys, participants also provided demographic details to provide a context to their attitudes to animals. As might be expected, and consistent with the validity of the new scale, overall scores on the AAS and APQ were highly correlated. However, the APQ provided a more differentiated measure of attitudes to animal use across a variety of settings. The results showed that there was overall higher levels of agreement with the use of animals in medical research and basic science, less endorsement for food production and pest control, and the use of animals for other cultural practices was generally disapproved of, irrespective of species. Participants overall disagreed with the use of rabbits, monkeys, badgers, tree shrews (survey 1), chimpanzees, dogs, dolphins and parrots (survey 2), but were neutral about the use of rats, mice, pigs, octopus, chickens, zebrafish (survey 1), carp, chickens, pigs, pigeons, rabbits and rats (survey 2). Interactions between species and purpose were largely driven by the consideration of using diverse species for food production. In general, females and vegetarians expressed less agreement with the use of animals with some differences by purpose of use. Pet keeping consistently predicted reduced willingness to use animals for basic science (only). The APQ provides a new tool to unpack how public attitudes depend on the intersectionality of demographics, species and purpose of use

Health specific traits beyond the Five Factor Model, cognitive processes and trait expression: replies to Watson (2012), Matthews (2012) and Haslam, Jetten, Reynolds, and Reicher (2012)

In this article we reply to the issues raised by the three commentaries on Ferguson's (2012) article. Watson argues that the four traits identified by Ferguson (2012) – health anxiety, alexithymia, empathy and Type D – do not lie outside the Five Factor Model (FFM). We present factor analytic data showing that health anxiety forms a separate factor from positive and negative affectivity, alexithymia forms a factor outside the FFM and while emotional empathy loads with agreeableness, cognitive empathy forms a separate factor outside the FFM. Across these analyses there was no evidence for a general factor of personality. We also show that health anxiety, empathic facets and alexithymia show incremental validity over FFM traits. However, the evidence that Type D lies outside the FFM is less clear. Matthews (2012) argues that traits have a more distributed influence on cognitions and that attention is not part of Ferguson's framework. We agree; but Ferguson's original statement concerned where traits have their maximal effect. Finally, Haslam et al. suggest that traits should be viewed from a dynamic interactionist perspective. This is in fact what Ferguson (2012) suggested and we go on to highlight that traits can also influence group processes

Commentary:considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product

Abstract Background The ‘trials within cohorts’ (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. Main text To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. Conclusion We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future

Selection of endogenous control genes for normalising gene expression data derived from formalin-fixed paraffin-embedded tumour tissue

From Springer Nature via Jisc Publications RouterHistory: received 2020-06-16, accepted 2020-09-28, registration 2020-10-01, online 2020-10-14, pub-electronic 2020-10-14, collection 2020-12Publication status: PublishedFunder: NIHRFunder: Mission Sector of the Egyptian Ministry of Higher Education and Scientific Research.Funder: CRUK; Grant(s): C147/A25254Abstract: Quantitative real time polymerase chain reaction (qPCR) data are normalised using endogenous control genes. We aimed to: (1) demonstrate a pathway to identify endogenous control genes for qPCR analysis of formalin-fixed paraffin-embedded (FFPE) tissue using bladder cancer as an exemplar; and (2) examine the influence of probe length and sample age on PCR amplification and co-expression of candidate genes on apparent expression stability. RNA was extracted from prospective and retrospective samples and subject to qPCR using TaqMan human endogenous control arrays or single tube assays. Gene stability ranking was assessed using coefficient of variation (CoV), GeNorm and NormFinder. Co-expressed genes were identified from The Cancer Genome Atlas (TCGA) using the on-line gene regression analysis tool GRACE. Cycle threshold (Ct) values were lower for prospective (19.49 ± 2.53) vs retrospective (23.8 ± 3.32) tissues (p < 0.001) and shorter vs longer probes. Co-expressed genes ranked as the most stable genes in the TCGA cohort by GeNorm when analysed together but ranked lower when analysed individually omitting co-expressed genes indicating bias. Stability values were < 1.5 for the 20 candidate genes in the prospective cohort. As they consistently ranked in the top ten by CoV, GeNorm and Normfinder, UBC, RPLP0, HMBS, GUSB, and TBP are the most suitable endogenous control genes for bladder cancer qPCR

Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.

Funder: Intramural Research Programs of the National Human Genome Research InstituteRegulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induce poor IL-10 responses and are functionally impaired. Moreover, metabolic supplementation with GGPP is able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells

Overshadowing depends on cue and reinforcement sensitivity but not schizotypy

There is evidence for impaired selective learning mechanisms in individuals high in schizotypy. Overshadowing provides a direct test of selective learning based on cue salience and has previously been reported to be impaired in relation to schizotypy scores. The present study tested for overshadowing using food allergy and Lego construction task variants. Both variants used the same number of conditioned stimulus (CS) cues and the same number of learning trials. CS cues were trained in compound pairs or in isolation and overshadowing was subsequently tested on trials followed by negative versus positive outcomes. Participants also completed the O-LIFE to measure schizotypy and BIS-BAS scales to measure reinforcement sensitivity. Learning was demonstrated for both cue variants; however overshadowing emerged only in the Lego variant and only on the trials followed by the negative outcome. Contrary to expectations, there was no evidence for any relationship between overshadowing and O-LIFE scores. However, there was evidence of a positive relationship between overshadowing and BAS-Drive as well as a negative relationship with BIS-Anxiety, for the trials followed by the positive outcome in the food allergy variant. These results suggest that the development of overshadowing depends on cue and reinforcement sensitivity, but not necessarily on schizotypy

Independence of HIF1a and androgen signaling pathways in prostate cancer

Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Abstract: Background: Therapeutic targeting of the androgen signaling pathway is a mainstay treatment for prostate cancer. Although initially effective, resistance to androgen targeted therapies develops followed by disease progression to castrate-resistant prostate cancer (CRPC). Hypoxia and HIF1a have been implicated in the development of resistance to androgen targeted therapies and progression to CRCP. The interplay between the androgen and hypoxia/HIF1a signaling axes was investigated. Methods: In vitro stable expression of HIF1a was established in the LNCaP cell line by physiological induction or retroviral transduction. Tumor xenografts with stable expression of HIF1a were established in castrated and non-castrated mouse models. Gene expression analysis identified transcriptional changes in response to androgen treatment, hypoxia and HIF1a. The binding sites of the AR and HIF transcription factors were identified using ChIP-seq. Results: Androgen and HIF1a signaling promoted proliferation in vitro and enhanced tumor growth in vivo. The stable expression of HIF1a in vivo restored tumor growth in the absence of endogenous androgens. Hypoxia reduced AR binding sites whereas HIF binding sites were increased with androgen treatment under hypoxia. Gene expression analysis identified seven genes that were upregulated both by AR and HIF1a, of which six were prognostic. Conclusions: The oncogenic AR, hypoxia and HIF1a pathways support prostate cancer development through independent signaling pathways and transcriptomic profiles. AR and hypoxia/HIF1a signaling pathways independently promote prostate cancer progression and therapeutic targeting of both pathways simultaneously is warranted