Regional Working in the East of England: Using the UK National Standards for Public Involvement

Plain English summary: Involving patients and members of the public to help shape and carry out research is recommended in health research in the United Kingdom (UK). There are a number of regional networks of Patient and Public Involvement (PPI) groups, which support the collaboration between researchers, patients and public members. We are a group of researchers, patients and public members who came together via a PPI regional network in the East of England to collaborate on a research study about the extent of feedback from researchers to PPI contributors.The aim of this paper is to use the recently developed UK National Standards for Public Involvement to structure our thinking about what worked well and what did not, within our recently completed study. We believe this paper is one of the first to use the National Standards to structure a retrospective reflection on PPI within a study.Our findings showed that there are benefits of regional working, including easier access to public members and bringing together researchers, public members and those who run PPI groups for research collaboration. The main challenges included involvement of people before studies are funded and working across organisations with different payment processes.The National Standards for Public Involvement has provided a useful framework to consider how best to involve patients and members of the public in research and could be a helpful structure to reflect on successes and challenges in individual projects and also regional, national or international comparisons of PPI in research. Abstract: Background Regional networks of Patient and Public Involvement (PPI) organisations, including academic institutions, health and social care services, charities, patient and public groups and individuals, can play an important part in carrying out health research. In the UK, recommendations by the National Institute of Health Research (NIHR) encourage the use of regional, collaborative networks with shared resources and training. Methods The newly developed UK National Standards for Public Involvement were used as a framework for a retrospective reflection of PPI within a recently completed research study which focused on feedback from researchers to PPI contributors. PPI contributors, those running PPI groups (PPI leads) and researchers involved in the study have contributed to this reflection by completing evaluation forms throughout the research alongside notes of meetings and co-authors' final reflections. Results Results revealed a number of successes where the regional network was particularly useful in bringing together PPI contributors, those who lead PPI groups and researchers. The regional network helped researchers to get in touch with patients and members of the public. Challenges included involving people before funding and bureaucratic and financial barriers when working across different organisations in the region. The importance of working together in flexible, informal ways was key and on-going support for the PPI contributors was vital for continued involvement, including emotional support not just monetary. The first four National Standards of inclusive opportunities, working together, support and learning and communications were particularly useful as means of structuring our reflections. Conclusions To our knowledge, this is one of the first research studies to use the UK National Standards for Public Involvement as a framework to identify what worked well and the challenges of PPI processes. It is suggested that as more reflective papers are published and the National Standards are more widely used in the UK, many lessons can be learnt and shared on how to improve our Patient and Public Involvement within research studies. Evaluations or reflections such as these can further enhance our understanding of PPI with implications for regional, national and international comparisons.Peer reviewedFinal Published versio

The Influence of Age-Related Differences in Prior Knowledge and Attentional Refreshing Opportunities on Episodic Memory

Objectives. The assumption that working memory (WM) is embedded within long-term memory suggests that the effectiveness of switching information between activated states in WM (i.e., attentional refreshing) may depend on whether that information is semantically relevant. Given that older adults often have greater general knowledge than younger adults, age-related deficits in episodic memory (EM) could be ameliorated by studying information that has existing semantic representations compared with unknown information. Method. Younger and older adults completed a modified operation span task that varied the number of refreshing opportunities. The memoranda used were equally known to younger and older adults (neutral words; e.g., father), better known to older adults than younger adults (dated words; e.g., mirth), or unknown to both groups (unknown words; e.g., cobot). Results. Results for immediate and delayed recall indicated an age-related improvement for dated memoranda and no age difference for unknown memoranda. Furthermore, refreshing opportunities predicted delayed recall of neutral memoranda more strongly for younger adults than older adults, whereas older adults' recall advantage for dated memoranda was explained by their prior knowledge and not refreshing opportunities. Discussion. The results suggest that older adults' EM deficits could potentially be ameliorated by incorporating their superior knowledge to supplement relatively ineffective attentional refreshing in WM

The Influence of Age-Related Differences in Prior Knowledge and Attentional Refreshing Opportunities on Episodic Memory

Objectives. The assumption that working memory (WM) is embedded within long-term memory suggests that the effectiveness of switching information between activated states in WM (i.e., attentional refreshing) may depend on whether that information is semantically relevant. Given that older adults often have greater general knowledge than younger adults, age-related deficits in episodic memory (EM) could be ameliorated by studying information that has existing semantic representations compared with unknown information. Method. Younger and older adults completed a modified operation span task that varied the number of refreshing opportunities. The memoranda used were equally known to younger and older adults (neutral words; e.g., father), better known to older adults than younger adults (dated words; e.g., mirth), or unknown to both groups (unknown words; e.g., cobot). Results. Results for immediate and delayed recall indicated an age-related improvement for dated memoranda and no age difference for unknown memoranda. Furthermore, refreshing opportunities predicted delayed recall of neutral memoranda more strongly for younger adults than older adults, whereas older adults' recall advantage for dated memoranda was explained by their prior knowledge and not refreshing opportunities. Discussion. The results suggest that older adults' EM deficits could potentially be ameliorated by incorporating their superior knowledge to supplement relatively ineffective attentional refreshing in W

A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

Background/Aims: Recessive mutations in the LHX3 homeodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods: Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results: A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the a-glycoprotein and PRL target genes. Conclusion: The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. copyright (C) 2012 S. Karger AG, Base

Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive state by RhoGDI1, which is found in a ternary complex with synectin and S4. Binding of S4 to synectin increases the latter's binding to RhoGDI1, which in turn enhances RhoGDI1's affinity for RhoG. S4 clustering activates PKCα, which phosphorylates RhoGDI1 at Ser96. This phosphorylation triggers release of RhoG, leading to polarized activation of Rac1. Thus, FGF2-induced Rac1 activation depends on the suppression of RhoG by a previously uncharacterized ternary S4–synectin–RhoGDI1 protein complex and activation via PKCα

Does smoking status affect the likelihood of consulting a doctor about respiratory symptoms? A pilot survey in Western Australia

<p>Abstract</p> <p>Background</p> <p>Smokers attribute respiratory symptoms, even when severe, to everyday causes and not as indicative of ill-health warranting medical attention. The aim of this pilot study was to conduct a structured vignette survey of people attending general practice to determine when they would advise a person with respiratory symptoms to consult a medical practitioner. Particular reference was made to smoking status and lung cancer.</p> <p>Methods</p> <p>Participants were recruited from two general practices in Western Australia. Respondents were invited to complete self-administered questionnaires containing nine vignettes chosen at random from a pool of sixty four vignettes, based on six clinical variables. Twenty eight vignettes described cases with at least 5% risk of cancer. For analysis these were dubbed 'cancer vignettes'. Respondents were asked if they would advise a significant other to consult a doctor with their respiratory symptoms. Logistic regression and non-parametric tests were used to analyse the data.</p> <p>Results</p> <p>Three hundred questionnaires were distributed and one hundred and forty completed responses were collected over six weeks. The majority (70.3%) of respondents were female aged forty and older. A history of six weeks' of symptoms, weight loss, cough and breathlessness independently increased the odds of recommending a consultation with a medical practitioner by a factor of 11.8, 2.11, 1.40 and 4.77 respectively. A history of smoking independently increased the odds of the person being thought 'likely' or 'very likely' to have cancer by a factor of 2.46. However only 32% of cancer vignettes with a history of cigarette smoking were recognised as presentations of possible cancer.</p> <p>Conclusion</p> <p>Even though a history of cigarette smoking was more likely to lead to the suggestion that a symptomatic person may have cancer we did not confirm that smokers would be more likely to be advised to consult a doctor, even when presenting with common symptoms of lung cancer.</p

Rapid calibration to dynamic temporal contexts

The prediction of future events and the preparation of appropriate behavioural reactions rely on an accurate perception of temporal regularities. In dynamic environments, temporal regularities are subject to slow and sudden changes, and adaptation to these changes is an important requirement for efficient behaviour. Bayesian models have proven a useful tool to understand the processing of temporal regularities in humans; yet an open question pertains to the degree of flexibility of the prior that is required for optimal modelling of behaviour. Here we directly compare dynamic models (with continuously changing prior expectations) and static models (a stable prior for each experimental session) with their ability to describe regression effects in interval timing. Our results show that dynamic Bayesian models are superior when describing the responses to slow, continuous environmental changes, whereas static models are more suitable to describe responses to sudden changes. In time perception research, these results will be informative for the choice of adequate computational models and enhance our understanding of the neuronal computations underlying human timing behaviour

Guidance for Researchers: Feedback : Patient and Public Involvement (PPI): Feedback from Researchers to PPI Contributors

© 2018 The Author(s). This an open access work distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited

Neurology

Contains reports on five research projects.United States Navy, Office of Naval Research (Nonr-609(39))United States Army Chemical Corps (DA-18-108-405-Cml-942)United States Air Force (Contract AF33(616)-7282)United States Public Health Service (B-3055, B-3090